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Reducing environmental pollution via elimination of sulfur compounds from gas condensate was the aim of this research. Whereby oxidative desulfurization from gas condensate with 3200 ppm initial sulfur was accomplished by hydrogen peroxide (30%wt) as oxidant and formic acid as catalyst. The sulfones after generation in the oxidation step were extracted through a method of liquid-liquid extraction by acetone as a polar solvent. The effects of variables: coefficient of oxidant to sulfur molar ratio (O/S), temperature (T), and coefficient of catalyst to oxidant molar ratio (C/O) were investigated. The experiments were designed with response surface methodology based on central composite design (CCD). The results of experiments demonstrated that none of these variables (O/S, T, and C/O) have any interaction, and among these variables, O/S plays a significant role with the most influence on desulfurization and C/O and T are of the second and third primary of importance, respectively. In addition, 86% desulfurization was obtained in the optimum conditions. [ABSTRACT FROM AUTHOR]

Objective(s): The current study reports investigation of codelivery by PLGA nanoparticles (NPs) loaded with crocetin (Cro), a natural carotenoid dicarboxylicHYPERLINK "http://en.wikipedia.org/wiki/Carboxylic_acid" acid that is found in the crocus flower, and Doxorubicin (DOX). Materials and Methods: Double emulsion/solvent evaporation method was used for preparation of PLGA nanoparticles containing Dox and Cro. Characterizations of prepared NPs were investigated by atomic force microscopy (AFM) and dynamic light scattering analysis. In vitro Cytotoxicity of DOX and Cro loaded PLGA NPs (PLGA-DOX-Cro) on MCF-7 cell line was evaluated using MTT test. Flow cytometry experiments were implemented to distinguish cells undergoing apoptosis from those undergoing necrosis. Furthermore the expression of caspase 3 was examined by western blot analysis. Results: The prepared formulations had size of 150- 300 nm. Furthermore, PLGA-DOX-Cro nanoparticles inhibited MCF-7 tumor cells growth more efficiently than either DOX or Cro alone at the same concentrations, as quantified by MTT assay and flow cytometry. Studies on cellular uptake of DOX-Cro-NPs demonstrated that NPs were effectively taken up by MCF-7 tumor cells. Conclusion: This study suggested that DOX-Cro-NPs may have promising applications in breast cancer therapy. [ABSTRACT FROM AUTHOR]

Multi drug resistance (MDR) is a serious obstacle in the management of breast cancer. Therefore, overcoming MDR using novel anticancer agents is a top priority for medicinal chemists. It was found that dihydropyridines lacking calcium antagonistic activity (e.g acridinediones) possess MDR modifier potency. In this study, the capability of four novel acridine-1,8-diones derivatives 3a-d were evaluated as MDR reversing agents. In addition, the relationship between structural properties and biological effects of synthesized compounds was discussed. In vitro cytotoxicity of acridine-1,8-diones 3a-d derivatives in combination with doxorubicin (DOX) on T47D and tomoxifen-resistant T47D (TAMR-6) breast cancer cell lines were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Drug resistant index (DRI), which is equal to the ratio of IC50 in drug-resistant cells over IC50 in drug-sensitive cells, was calculated for each substance. Flowcytometry experiments were also implemented to distinguish cells undergoing apoptosis from those undergoing necrosis. The results from MTT and flowcytometry experiments indicated that 1 nM 3c derivative along with DOX significantly (P<0.05) increased the DOX cytotoxicity in T47D and TAMR-6 breast cancer cell lines. Synthesized compounds 3a and 3b also at concentrations of 1 nM with DOX significantly increased the cytotoxicity of DOX on T47D and TAMR-6 breast cancer cell lines. Meanwhile, 3d derivative with DOX did not exhibit good synergistic effect on cytotoxic activity of DOX, and slightly increased DOX cytotoxicity in both cell lines. Our results proposed that 3c may be an attractive lead compound for further development as a chemotherapeutic agent for MDR breast cancer therapy in combination with routine chemotherapeutic agents such as DOX. [ABSTRACT FROM AUTHOR]

In the current study, a core-shell inorganic nanostructure comprising a gold nanorod core and -mesoporous manganese dioxide shell was synthesized. Then, the mesoporous manganese dioxide shell was loaded with doxorubicin (DOX) and then coated with pluronic F127 and pluronic F127-folic acid conjugate (1.5:1 wt ratio of pluronic F127: pluronic F127-folic acid conjugate) to prepare targeted final platform. In this design, mesoporous manganese dioxide acted as a reservoir for DOX loading, anti-hypoxia, and MRI contrast agent, while the gold nanorod core acted as a photothermal and CT scan imaging agent. DOX was encapsulated in the mesoporous manganese dioxide shell with a loading capacity and loading efficiency of 19.8 % ± 0.2 and 99.0 % ± 0.9, respectively. The in vitro release experiment showed the impact of glutathione (GSH), mildly acidic pH, and laser irradiating toward accelerated stimuli-responsive DOX release. The ·OH production of the prepared platform was verified by methylene blue (MB) decomposition reaction. Furthermore, thermal imaging exhibited the ability of the prepared platform to convert the NIR irradiation to heat. In vitro cytotoxicity tests on the folate receptor-positive 4 T1 cell line revealed the remarkable cytotoxicity of the targeted formulation compared to the nontargeted formulation (statistically significant). The MTT experiment demonstrated that exposure to laser 808 irradiation enhanced cytotoxicity of the targeted formulation (p < 0.0001). The production of ROS in 4 T1 cells following treatment with the targeted formulation was demonstrated by the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. Furthermore, in vivo investigations by implementing subcutaneous 4 T1 tumorized female BABL/c mice indicated that the prepared platform was an effective system in suppressing tumor growth by combining chemotherapy with PTT (photothermal therapy). Additionally, simultanous PTT and anti-hypoxic activity of this system showed potent tumor growth suppression impact. The percent of tumor size reduction in mice treated with FA-F127-DOX@Au-MnO 2  + 808 nm laser compared to the control group was 99.7 %. The results of the biodistribution investigation showed tumor accumulation and modified pharmacokinetics of the targeted system. Lastly, 6 and 24 h post-intravenous injection, CT-scan and MR imagings capability of the prepared platform was verified in preclinical stage. The prepared multipurpose system introduces great opportunity to provide multiple treatment strategy along with multimodal imaging capability in a single platform for breast cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Due to the exceedingly poisonous properties of Pb 2+ , it is imperative to conduct a thorough assessment of its quantity in both biological and environmental samples, as this is crucial for safeguarding public health. This study describes an economic turn-off fluorescent aptasensor for the quantitative analysis of Pb 2+ employing 3,4,9,10-perylenetetracarboxylic acid diimide (PTCDI) as a cost-effective fluorophore, gold nanoparticles (AuNPs) as separating agent and an elongated aptamer as both targeting agent and PTCDI loading site. The fundamental principle of the suggested fluorescent aptasensor, which is based on PTCDI, relies on detecting variations in the fluorescence intensity of PTCDI when an elongated aptamer (as single-stranded DNA) is present or absent. The advanced aptasensor is advantageous due to the elongation of the lead aptamer sequence length induced by terminal deoxynucleotidyl transferase (TdT), resulting in enhanced sensitivity. The presence of Pb 2+ and the centrifugation process causes the separation of the poly A-modified aptamer/Pb 2+ conjugate from the poly T sequence. Hence, the interaction of PTCDI with the poly A moiety in the modified aptamer leads to a decrease in its fluorescence emission. The findings showcased that the fluorescent aptasensor exhibited exceptional specificity towards Pb 2+ ions, while the biosensing platform accomplished an impressive detection limit of 3.7 pM. Moreover, the suggested aptasensor utilizing PTCDI exhibits a commendable capability in quantitatively analyzing Pb 2+ within human serum samples and mineral water., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the current study, a tumor microenvironment responsive (TME-responsive) copper peroxide-mesoporous silica core-shell structure with H 2 O 2 self-supplying ability was fabricated for targeted ferroptosis/chemotherapy against metastatic breast cancer. At the first stage, copper peroxide nanodot was synthesized and subsequently coated with mesoporous organosilica shell. After (3-Aminopropyl) triethoxysilane (APTMS) functionalization of the organosilica shell, doxorubicin (DOX) was loaded in the mesoporous structure of the nanoparticles and then, heterofunctional COOH-PEG-Maleimide was decorated on the surface through EDC/NHS chemistry. Afterward, thiol-functionalized AS1411 aptamer was conjugated to the maleimide groups of the PEGylated nanoparticles. In vitro study illustrated ROS generation of the system in the treated 4 T1 cell. Cellular uptake and cytotoxicity experiments showed enhanced internalization and cytotoxicity of the targeted system comparing to non-targeted one. The in vivo study on ectopic 4 T1 tumor induced in Female BALB/c mice showed ideal therapeutic effect of Apt-PEG-Silica-DOT@DOX with approximately 90 % tumor suppression in comparison with 50 % and 25 % tumor suppression for PEG-Silica-DOT@DOX and PEG-Silica-DOT. Moreover, Apt-PEG-Silica-DOT@DOX provide favorable characteristics for biosafety issues concerning the rate of survival and loss of body weight. The prepared platform could serve as a multifunctional system with smart behavior in drug release, tumor accumulation and capable for ferroptosis/chemotherapy against breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Combination therapy using chemo-photothermal therapy (chemo-PTT) shows great efficacy toward tumor ablation in preclinical studies. Besides, lipopolymersomes as a hybrid nanocarriers, integrate advantages of liposomes and polymersomes in a single platform in order to provide tremendous biocompatibility, biodegradability, noteworthy loading efficacy for both hydrophobic and hydrophilic drugs with adjustable drug release and high stability. In this study, a multipurpose lipopolymersome was fabricated for guided chemotherapy-PTT and NIR-imaging of melanoma. A lipopolymerosomal hybrid nanovesicle consisting of equal molar ratio of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) diblock copolymer (molar ratio 1:1) was fabricated. The nanoparticulate system was prepared through film rehydration technique for encapsulation of doxorubicin (DOX) and indocyanine green (ICG) to form DOX-ICG-LP platform. At the next stage, AS1411 DNA aptamer was conjugated to the surface of lipopolymersome (Apt-DOX-ICG-LP) for selective delivery. The sizes of DOX-ICG-LP and Apt-DOX-ICG-LP were obtained through DLS analysis (61.0 ± 6 and 74 ± 5, respectively). Near Infrared-responsive release pattern of the prepared lipopolymersome was verified in vitro. The formulated platform showed efficient photothermal conversion, and superior stability with acceptable encapsulation efficiency. Consistent with the in vitro studies, NIR-responsive lipopolymersome exhibited significantly higher cellular toxicity for Chemo-PTT versus single anti-cancer treatment. Moreover, superlative tumor shrinkage with favorable survival profile were attained in B16F10 tumor-bearing mice received Apt-DOX-ICG-LP and irradiated with 808 nm laser compared to those treated with either DOX-ICG-LP or Apt-DOX-ICG-LP without laser irradiation. The diagnostic capability of Apt-DOX-ICG-LP was addressed using in vivo NIR imaging, 6 and 24 h post-intravenous administration. The results indicated desirable feature of an established targeted theranostic capability of Apt-DOX-ICG-LP for both diagnostics and dual chemo-PTT of melanoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chemotherapy as a common anticancer therapeutic modality is often challenged by various obstacles such as poor stability, low solubility, and severe side effects of chemotherapeutic agents as well as multidrug resistance of cancerous cells. Nanoparticles in the role of carriers for chemotherapeutic drugs and platforms for combining different therapeutic approaches have effectively participated in overcoming such drawbacks. In particular, nanoparticles able to induce their therapeutic effect in response to specific stimuli like tumor microenvironment characteristics (e.g., hypoxia, acidic pH, high levels of glutathione, and overexpressed hydrogen peroxide) or extrinsic stimulus of laser light bring about more precise and selective treatments. Among them, nanostructures of covalent organic frameworks (COFs) have drawn great interest in biomedical fields during recent years. Possessing large surface area, high porosity, structural stability, and customizable architecture, these biocompatible porous crystalline polymers properly translate to promising platforms for drug delivery and induction of combination therapies. With the focus on stimuli-responsive characteristics of nanoscale COFs, this study aims to propose an overview of their potentiality in cancer treatment on the basis of chemotherapy alone or in combination with sonodynamic, chemodynamic, photodynamic, and photothermal therapies.

Breast cancer treatment can be challenging, but a targeted drug delivery system (DDS) has the potential to make it more effective and reduce side effects. This study presents a novel nanotherapeutic targeted DDS developed through the self-assembly of an amphiphilic di-block copolymer to deliver the chemotherapy drug SN38 specifically to breast cancer cells. The vehicle was constructed from the PHPMA-b-PEAMA diblock copolymer synthesized via RAFT polymerization. A single emulsion method was then used to encapsulate SN38 within nanoparticles (NPs) formed from the PHPMA-b-PEAMA copolymer. The AS1411 DNA aptamer was covalently bonded to the surface of the micellar NPs, producing a targeted DDS. Molecular dynamics (MD) simulation studies were also performed on the di block polymeric system, demonstrating that SN38 interacted well with the di block. The in vitro results demonstrated that AS1411- decorated SN38-loaded HPMA NPs were highly toxic to breast cancer cells while having a minimal effect on non-cancerous cells. Remarkably, in vivo studies elucidated the ability of the targeted DDS to enhance the antitumor effect of SN38, suppressing tumor growth and improving survival rates compared to free SN38., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, a platform was fabricated by combining a cationic lipid, 1,2-Dioleoyl-3-trimethylammonium-propane (DOTAP) with mesenchymal stem cell membrane (MSCM) to produce a positively charged hybrid vesicle. The prepared hybrid vesicle was used to condense BIRC5 CRISPR/Cas9 plasmid for survivin (BIRC5) gene editing. The Sgc8-c aptamer (against protein tyrosine kinase 7) was then attached to the surface of the prepared NPs through electrostatic interactions. In this regard, melanoma cancer cells (B16F0 cell line) overexpressing PTK7 receptor could be targeted. Investigations were conducted on this system to evaluate its transfection efficiency, cellular toxicity, and therapeutic performance in preclinical stage using B16F0 tumor bearing C57BL/6 J mice. The results verified the superiority of the Hybrid/ BIRC5 compared to Liposome/ BIRC5 in terms of cellular toxicity and transfection efficiency. The cells exposure to Hybrid/BIRC5 significantly enhanced cytotoxicity. Moreover, cells treated with Apt-Hybrid/BIRC5 showed higher anti-proliferation activity toward PTK7-positive B16F0 cancer cells than that of the PKT7-negative CHO cell line. The active tumor targeting nanoparticles increased the cytotoxicity through down-regulation of BIRC5 expression as confirmed by Western blot analysis. In preclinical stage, Apt-Hybrid/BIRC5 showed remarkable tumor growth suppression toward B16F0 tumorized mice. Thus, our study suggested that genome editing for BIRC5 through the CRISPR/Cas9 system could provide a potentially safe approach for melanoma cancer therapy and has great potential for clinical translation., Competing Interests: Declaration of competing interest The authors affirm that they possess no recognized conflicting financial interests or personal associations that may have seemed to impact the research presented in this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The objective of this investigation was to develop a self-assembled, dual-functionalized delivery system that could effectively transport doxorubicin (DOX) to cancer cells through the use of AS1411 aptamer and hyaluronic acid polymer (HA). The ultimate goal is an improved targeting approach for more efficient treatment. The core of this system comprised polyethylenimine (PEI) and FOXM1 aptamer, which was coated by HA. Next, nucleolin targeting aptamers (AS1411) were loaded onto the nanocomplex. Afterward, DOX was added to Aptamers (Apts)-HA-PEI-FOXM1 NPs to create the DOX-AS1411-HA-PEI-FOXM1 NPs for better treatment of cancer cells. The cytotoxic effect of the nanocomplex on L929, 4T1, and A549 cells showed that cell mortality in target cancer cells (4T1 and A549) was considerably enhanced compared to nontarget cells (L929, normal cells). The findings from the flow cytometry analysis and fluorescence imaging demonstrated the cellular absorption of DOX-Apts-HA-PEI-FOXM1 NPs in target cells was significantly enhanced when compared to L929 cells. Furthermore, in vivo antitumor study exhibited that DOX-Apts-HA-PEI-FOXM1 NPs rendered specific tumor accumulation and increasing of the anti-tumor effects., Competing Interests: Declaration of competing interest There is no conflict of interest about this article., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Targeting actionable mutations in oncogene-driven cancers and the evolution of immuno-oncology are the two prominent revolutions that have influenced cancer treatment paradigms and caused the emergence of precision oncology. However, intertumoral and intratumoral heterogeneity are the main challenges in both fields of precision cancer treatment. In other words, finding a universal marker or pathway in patients suffering from a particular type of cancer is challenging. Therefore, targeting a single hallmark or pathway with a single targeted therapeutic will not be efficient for fighting against tumor heterogeneity. Mesenchymal stem cells (MSCs) possess favorable characteristics for cellular therapy, including their hypoimmune nature, inherent tumor-tropism property, straightforward isolation, and multilineage differentiation potential. MSCs can be loaded with various chemotherapeutics and oncolytic viruses. The combination of these intrinsic features with the possibility of genetic manipulation makes them a versatile tumor delivery vehicle that can be used for in vivo selective tumor delivery of various chemotherapeutic and biological therapeutics. MSCs can be used as biofactory for the local production of chemical or biological anticancer agents at the tumor site. MSC-mediated immunotherapy could facilitate the sustained release of immunotherapeutic agents specifically at the tumor site, and allow for the achievement of therapeutic concentrations without the need for repetitive systemic administration of high therapeutic doses. Despite the enthusiasm evoked by preclinical studies that used MSC in various cancer therapy approaches, the translation of MSCs into clinical applications has faced serious challenges. This manuscript, with a critical viewpoint, reviewed the preclinical and clinical studies that have evaluated MSCs as a selective tumor delivery tool in various cancer therapy approaches, including gene therapy, immunotherapy, and chemotherapy. Then, the novel nanotechnology and bioengineering approaches that can improve the potency of MSC for tumor targeting and overcoming challenges related to their low localization at the tumor sites are discussed., (© 2024 Wiley Periodicals LLC.)

Here, a novel targeted nanostructure complex was designed as an alternative to the traditional treatment approaches for breast cancer. A delivery system utilizing CuS nanoparticles (CuS NPs) was developed for the purpose of targeted administration of doxorubicin (Dox), an anticancer agent. To regulate Dox release, chitosan (CS), a biodegradable and hydrophilic polymer with biocompatible properties, was applied to coat the Dox-loaded CuS NPs. Furthermore, AS1411 aptamer, served as a targeting agent for breast cancer cells (MCF-7 and 4T1 cells), was conjugated with CS-Dox-CuS NPs effectively. To assess the effectiveness of APT-CS-CuS NPs, various methods such as flow cytometry analysis, MTT assay, fluorescence imaging, and in vivo antitumor efficacy were employed. The hollow core and porous surface of CuS NPs improved the Dox loading capacity and entrapment efficiency (almost 100%). The rate of drug release at the tumor site (citrate buffer with pH 5.6) exhibited a marked increase in comparison to that observed within the physiological environment (phosphate buffer with pH 7.4). The targeted formulation (APT-CS-Dox-CuS NPs) significantly increased cytotoxicity of the Dox payload in target cells, including 4T1 (p ≤ 0.0001 (****)) and MCF7 (p ≤ 0.01 (**)) cells compared to CHO cells. Moreover, the ability of tumor growth inhibition of the targeted system was significantly (p ≤ 0.05 (*)) more than free Dox in tumor-bearing mice. The findings indicate that the targeted formulation augmented effectiveness and specificity while minimizing harm to non-targeted cells, signifying its potential as a sophisticated cancer drug delivery system., Competing Interests: Declaration of competing interest There is no conflict of interest about this article., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Aims: Resveratrol (RSV) is a polyphenolic substance found in numerous natural products. Despite the wide range of therapeutic activities, including antioxidant and anti-inflammatory effects, the poor pharmacokinetic characteristics decrease the RSV bioavailability following oral administration. Milk-derived exosomes (MEXOs), as a class of natural nanocarriers, are promising candidates for oral drug delivery approaches., Main Methods: The current study developed RSV-loaded MEXOs to enhance the RSV oral bioavailability, introducing a suitable exosomal formulation for suppressing colon inflammation in acetic acid-induced rat models., Key Findings: The results showed a remarkable encapsulation efficiency of 83.33 %. The in vitro release profile demonstrated a good retaining capability in acidic conditions (pH 1.2) and a considerable release in a simulated duodenal environment (pH 6.8). According to the permeability study, encapsulation of RSV improved its transportation across the Caco-2 monolayer. Moreover, the in vivo and histological analysis results proved that the RSV-MEXOs formulation successfully alleviates the inflammation in colitis rat models and effectively relieves the colitis., Significance: Our findings suggest that MEXOs should be of great attention as promising oral drug delivery vehicles for further clinical evaluations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Given the highly mutagenic and carcinogenic nature of Aflatoxin M1 (AFM1), the quantity assessment of AFM1 residues in milk and dairy products is necessary to maintain consumer health and food safety. Herein, CRISPR-Cas12a-based colorimetric aptasensor was developed using the catalytic activity of flower-like nanozymes of MnO 2 and trans-cleavage property of CRISPR-Cas12a system to quantitatively detect AFM1. The basis of the developed colorimetric aptasensor relies on whether or not the CRISPR-Cas12a system is activated, as well as the contrast in oxidase-mimicking capability exhibited by flower-like MnO 2 nanozymes when AFM1 is absent or present. When AFM1 is not present in the sample, single-stranded DNA (ssDNA) is degraded by the activated CRISPR-Cas12a, and the solution turns into yellow due to the catalytic activity of the nanozymes. While, in the attendance of AFM1, ssDNA degradation does not occur due to the inactivation of the CRISPR-Cas12a. Therefore, with the adsorption of the ssDNA on the MnO 2 nanozymes, their catalytic activity decreases, and the solution color becomes pale yellow due to less oxidation of the chromogenic substrate. In this aptasensor, the relative absorbance changes increased linearly from 6 to 160 ng L -1 , and the detection limit was 2.1 ng L -1 . The developed aptasensor displays a selective detection performance and a practical application for quantitative analysis of AFM1 in milk samples. The results of the introduced aptasensor open up the way to design other selective and sensitive aptasensors for the detection of other mycotoxins by substitution of the used sequences., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Liquid crystalline nanoparticles (LCNPs) have gained much attention in cancer nanomedicines due to their unique features such as high surface area, storage stability, and sustained-release profile. In the current study, a novel LCNP for co-encapsulation of Bi 2 O 3 and hydrophilic doxorubicin (DOX) was fabricated and functionalized with folic acid (FA) to achieve efficient tumor targeting toward CT-scan imaging and chemotherapy of melanoma in vitro and in vivo. LCNPs Bi 2 O 3 NPs were prepared using glycerol monooleate-pluronic F-127 (GMO/PF127/water). Firstly, GMO/water were homogenized to prepare LC gel. Then, the stabilizer aqueous solution (PF127/Bi 2 O 3 /DOX) was added to the prepared LC gel and homogenized using homogenization and ultrasonication. The formulated NPs exhibited superior stability with encapsulation efficiency. High cytotoxicity and cellular internalization of the FA-Bi 2 O 3 -DOX-NPs were observed in comparison with Bi 2 O 3 -DOX-NPs and the free DOX in folate-receptor (FR) overexpressing cells (B 16 F 10 ) in vitro. Moreover, ideal tumor suppression with increased survival rate were observed in tumorized mice treated with FA-Bi 2 O 3 -DOX-NPs compared to those treated with non-targeted one. On the other hand, the CT-imaging ability of the Bi 2 O 3 -DOX-NPs was tested inB 16 F 10 tumor-bearing mice. The obtained data indicated a high potential of the developed targeted theranostic FA-Bi 2 O 3 -DOX-NPs for diagnostics and treatment of melanoma., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Due to its inherent membrane structure, a nanostructure enveloped by an active cell membrane possesses distinctive characteristics such as prolonged presence in the bloodstream, precise identification capabilities, and evasion of immune responses. This research involved the production of biomimetic nanoparticles, specifically hollow gold nanoparticles (HGNPs) loaded with methotrexate (MTX), which were further coated with cancer cell membrane. These nanoparticles were then adorned with AS1411 aptamer to serve as a targeting agent (Apt-CCM-HG@MTX). The nanoplatform demonstrated precise targeting towards cancer cells due to its dual-targeting characteristic (AS1411 aptamer and C26 cancer cell membrane), exhibiting uniformity in distribution. It also displayed a desirable response to photothermal stimulation, controlled release of drugs, and exceptional properties for fluorescence imaging. The system was composed of spherical HGNPs measuring 51.33 ± 5.70 nm in diameter, which were effectively loaded with MTX using a physical absorption method. The encapsulation efficiency achieved was recorded at 79.54 %, while the loading efficiency reached 38.21 %. The targeted formulation demonstrated a noteworthy mortality of approximately 45 % in the nucleolin positive cell line, C26, as determined by in vitro cytotoxicity assays. As a result of the functionalization process applied to the homologous binding adhesion molecules found in cancer cell membranes and targeting ability of AS1411 aptamer, Apt-CCM-HG@MTX demonstrated a substantial enhancement in targeting tumors and facilitating cellular uptake during in vivo experiments. Furthermore, under NIR radiation the photothermal effect exhibited by Apt-CCM-HG@MTX in the tumor area was notably robust due to the distinctive attributes of HGNPs. The conclusions obtained from this study have the potential to assist in adopting a bioinspired strategy that will significantly improve the effective management of MTX and therapy for individuals with colorectal cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Thrombin, a proteolytic enzyme, plays an essential role in catalyzing many blood clotting reactions. Thrombin can act as a marker for some blood-related diseases, such as leukemia, thrombosis, Alzheimer's disease and liver disease. Therefore, its diagnosis is of great importance in the fields of biological and medical research. Biosensors containing sandwich-type structures have attracted much consideration owing to their superior features such as reproducible and stable responses with easy improvement in the sensitivity of detection. Sandwich-type platforms can be designed using a pair of receptors that are able to bind to diverse locations of the same target. Herein, we investigate recent advances in the progress and applications of thrombin aptasensors containing a sandwich-type structure, in which two thrombin-binding aptamers (TBAs) identify different parts of the thrombin molecule, leading to the formation of a sandwich structure and ultimately signal detection. We also discuss the pros and cons of these approaches and outline the most logical approach in each section.

Mesenchymal stem cells (MSCs) have been extensively used in various therapeutic applications over the last two decades, particularly in regenerative medicine and cancer treatment. MSCs have the ability to differentiate into mesodermal and non-mesodermal lineages, which makes them a popular choice in tissue engineering and regenerative medicine. Studies have shown that MSCs have inherent tumor-suppressive properties and can affect the behavior of multiple cells contributing to tumor development. Additionally, MSCs possess a tumor tropism property and have a hypoimmune nature. The intrinsic features of MSCs along with their potential to undergo genetic manipulation and be loaded with various anticancer therapeutics have motivated researchers to use them in different cancer therapy approaches without considering their complex dynamic biological aspects. However, despite their desirable features, several reports have shown that MSCs possess tumor-supportive properties. These contradictory results signify the sophisticated nature of MSCs and warn against the potential therapeutic applications of MSCs. Therefore, researchers should meticulously consider the biological properties of MSCs in preclinical and clinical studies to avoid any undesirable outcomes. This manuscript reviews preclinical studies on MSCs and cancer from the last two decades, discusses how MSC properties affect tumor progression and explains the mechanisms behind tumor suppressive and supportive functions. It also highlights critical cellular pathways that could be targeted in future studies to improve the safety and effectiveness of MSC-based therapies for cancer treatment. The insights obtained from this study will pave the way for further clinical research on MSCs and development of more effective cancer treatments., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The combination of nanomaterials possessing distinct characteristics and the precision of aptamers facilitates the creation of biosensors that exhibit exceptional selectivity and sensitivity. In this manuscript, we present a highly sensitive aptasensor that utilizes the distinctive characteristics of MnO 2 nanoflowers and gold nanoparticles to selectively detect ampicillin (AMP). In this aptasensor, the mechanism of signal change is attributed to the difference in the oxidase-mimicking activity of MnO 2 nanoflowers in the presence of a free sequence. The inclusion of AMP hindered the creation of a double-stranded DNA configuration through its binding to the aptamer, resulting in an observable alteration in absorbance. The relative absorbance varied linearly with the concentration of AMP in the range of 70 pM to 10 nM with a detection limit of 21.7 pM. In general, the colorimetric aptasensor that has been developed exhibits exceptional selectivity and remarkable stability. It also demonstrates favorable performance in human serum, making it a highly reliable diagnostic tool. Additionally, its versatility is noteworthy as it holds great potential for detecting various antibiotics present in complex samples by merely replacing the utilized sequences with new ones., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Conventional cancer therapies with chemodrugs suffer from various disadvantages, such as irreversible side effects on the skin, heart, liver, and nerves with even fatal consequences. RNA-based therapeutic is a novel technology which offers great potential as non-toxic, non-infectious, and well-tolerable platform. Herein, we introduce different RNA-based platforms with a special focus on siRNA, miRNA, and mRNA applications in cancer treatment in order to better understand the details of their therapeutic effects. Of note, the co-delivery of RNAs with other distinct RNA or drugs has provided safe, efficient, and novel treatment modalities for cancer treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cytokines are the first modern immunotherapeutic agents used for activation immunotherapy. Interleukin-18 (IL-18) has emerged as a potent anticancer immunostimulatory cytokine over the past three decades. IL-18, structurally is a stable protein with very low toxicity at biological doses. IL-18 promotes the process of antigen presentation and also enhances innate and acquired immune responses. It can induce the production of proinflammatory cytokines and increase tumor infiltration of effector immune cells to revert the immunosuppressive milieu of tumors. Furthermore, IL-18 can reduce tumorigenesis, suppress tumor angiogenesis, and induce tumor cell apoptosis. These characteristics present IL-18 as a promising option for cancer immunotherapy. Although several preclinical studies have reported the immunotherapeutic potential of IL-18, clinical trials using it as a monotherapy agent have reported disappointing results. These results may be due to some biological characteristics of IL-18. Several bioengineering approaches have been successfully used to correct its defects as a bioadjuvant. Currently, the challenge with this anticancer immunotherapeutic agent is mainly how to use its capabilities in a rational combinatorial therapy for clinical applications. The present study discussed the strengths and weaknesses of IL-18 as an immunotherapeutic agent, followed by comprehensive review of various promising bioengineering approaches that have been used to overcome its disadvantages. Finally, this study highlights the promising application of IL-18 in modern combinatorial therapies, such as chemotherapy, immune checkpoint blockade therapy, cell-based immunotherapy and cancer vaccines to guide future studies, circumventing the barriers to administration of IL-18 for clinical applications, and bring it to fruition as a potent immunotherapy agent in cancer treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Lead (Pb 2+ ) is one of the most toxic heavy metals, and its environmental pollution and serious damages is a global concern. Therefore, it is necessary to develop effective sensing methods. This study describes a new strategy for the design of label-free competitive time-resolved fluorescent (TRF) aptasensor for detecting Pb 2+ ions. The sensing principle of this aptasensor is the competition between Pb 2+ and Tb 3+ ions to bind to the guanine/thymine-rich sequence (lead aptamer) and the sensitized luminescence of Tb 3+ by this sequence. The developed TRF aptasensor demonstrated a good linear detection range from 2.5 nM to 150 nM and a limit of detection (LOD) of 645 pM. In addition, the proposed TRF aptasensor has a high selectivity towards Pb 2+ , and it has also been successfully utilized to detect this ion in milk and human serum samples. This TRF aptasensor offers advantages such as short analysis time, simple operation, low cost, being label-free, and surpassing the interference of background fluorescence of biological samples due to its TRF characteristic. In this paper, we propose a Tb 3+ /guanine/thymine-rich sequence system for designing different aptasensors against diverse targets by applying a proper guanine-rich sequence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rolling circle amplification (RCA) process as an excellent DNA amplifier strategy possesses the merits of high performance and easy operation. In this research, a sensitive RCA-based fluorescent aptasensor was fabricated for the detection of kanamycin residues in food. The aptasensing approach consisted of two main steps; immobilization of biotinylated kanamycin aptamer on streptavidin magnetic beads (SMB) and separation of free complementary strands (CS) from the SMB-aptamer/kanamycin at the first step. For the second step, RCA procedure was applied as signal magnifier and SYBR Green was added as fluorescent indicator dye. The linear relation between the aptasensor response and kanamycin concentration was obtained from 5 nM to 100 nM with the detection limit of 1.93 nM (S/N = 3). The aptasensor displayed satisfactory selectivity among other antibiotics. The developed aptasensor is reliable for monitoring kanamycin in milk as a common foodstuff., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chemotherapy has been widely acknowledged as a primary approach for cancer treatment. However, the administration of chemotherapy agents is often limited by their adverse effects that result from an inability to distinguish between healthy and malignant cells. As such, utilising nanocarriers in targeted drug delivery can significantly reduce these side effects while enhancing therapeutic efficacy. Herein, we developed copper sulphide nanoparticles (CuSNPs) loaded with epirubicin (Epi) coated by polyarginine and 5TR1 aptamer (CEPA) to target mucin-1 which is overexpressed on various types of cancer cells. MTT results revealed that CEPA significantly induced cytotoxicity of the drug in desired cell lines (C26 and MCF-7, mucin + ) compared to CEPA-treated CHO cells (non-target, mucin - ), verifying the targeting ability of CEPA complex. The obtained results from both flow cytometry analysis and cell imaging demonstrated that CEPA complex had successful internalisation in both target cell lines but no internalisation in CHO cell line. The result of in vivo assay showed more tumour inhibition and more accumulation in tumour tissue for CEPA complex in comparison to free Epi. To conclude, the CEPA complex has demonstrated superior efficacy and fewer adverse reactions compared to Epi. This indicates a promising and effective strategy for treating cancer.

Due to the limitations of conventional cancer treatment methods, nanomedicine has appeared as a promising alternative, allowing improved drug targeting and decreased drug toxicity. In the development of cancer nanomedicines, among various nanoparticles (NPs), DNA nanostructures are more attractive because of their precisely controllable size, shape, excellent biocompatibility, programmability, biodegradability, and facile functionalization. Aptamers are introduced as single-stranded RNA or DNA molecules with recognize their corresponding targets. So, incorporating aptamers into DNA nanostructures led to influential vehicles for bioimaging and biosensing as well as targeted cancer therapy. In this review, the recent developments in the application of aptamer-based DNA origami and DNA nanostructures in advanced cancer treatment have been highlighted. Some of the main methods of cancer treatment are classified as chemo-, gene-, photodynamic- and combined therapy. Finally, the opportunities and problems for targeted DNA aptamer-based nanocarriers for medicinal applications have also been discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The fluorescence assay is one of the popular methods that is applied for detection of different targets. However, this method may show low sensitivity and high background in biological samples due to the natural fluorescence of different compounds in complicated samples. In addition, it inevitably affects the detection results accuracy. A fundamental solution to this problem is the use of the time-resolved fluorescence technique (TRF). The main component of this technique is the use of long fluorescence lifetime reagents. In this review, various time-resolved fluorescent reagents such as complexes of lanthanide ions, lanthanide-doped inorganic nanoparticles; Mn-doped ZnS quantum dots (QDs) and pyrene excimer are introduced. Moreover, TRF sensors, especially TRF aptasensors (DNA-based sensors) are discussed. This review will give new ideas for researchers to develop novel high-sensitive TRF sensors that can remove or decrease background fluorescence and use them for the detection of various targets in complicated samples without treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The formation of polymeric micelles in aqueous environments through the self-assembly of amphiphilic polymers can provide a versatile platform to increase the solubility and permeability of hydrophobic drugs and pave the way for their administration. In comparison to various self-assembly-based vehicles, polymeric micelles commonly have a smaller size, spherical morphology, and simpler scale up process. The use of polymer-based micelles for the encapsulation and carrying of therapeutics to the site of action triggered a line of research on the synthesis of various amphiphilic polymers in the past few decades. The extended knowledge on polymers includes biocompatible smart amphiphilic copolymers for the formation of micelles, therapeutics loading and response to external stimuli, micelles with a tunable drug release pattern, etc. Different strategies such as ring-opening polymerization, atom transfer radical polymerization, reversible addition-fragmentation chain-transfer, nitroxide mediated polymerization, and a combination of these methods were employed to synthesize copolymers with diverse compositions and topologies with the proficiency of self-assembly into well-defined micellar structures. The current review provides a summary of the important polymerization techniques and recent achievements in the field of drug delivery using micellar systems. This review proposes new visions for the design and synthesis of innovative potent amphiphilic polymers in order to benefit from their application in drug delivery fields.

Objective: Herein, a dual-targeting delivery system using mesoporous silica nanoparticles with hollow structures (HMSNs) was developed for the specific delivery of epirubicin (EPI) to cancer cells and introducing a H + -triggered bubble generating nanosystem (BGNS). HMSNs containing EPI are covered by hyaluronic acid (HA) shell and AS1411 aptamer to create the BGNS-EPI-HA-Apt complex, which is highly selective against CD44 marker and nucleolin overexpressed on the surface of tumor cells., Methods: MTT assay compared the cytotoxicity of different treatments in CHO (Chinese hamster ovary) cells as well as 4T1 (murine mammary carcinoma) and MCF-7 (human breast adenocarcinoma) cells. The internalization of Epi was assessed by flow cytometry along with fluorescence imaging. In vivo studies were conducted on BALB/c mice bearing a tumor from 4T1 cell line where monitoring included measuring tumor volume, mouse weight changes over time alongside mortality rate; accumulation levels for Epi within organs were also measured during this process., Results: The collected data illustrated that BGNS-EPI-HA-Apt complex controlled the release of EPI in a sustained method. Afterward, receptor-mediated internalization via nucleolin and CD44 was verified in 4T1 and MCF-7 cells using fluorescence microscopy assay and flow cytometry analysis. The results of tumor inhibitory effect study exhibited that BGNS-EPI-HA-Apt complex decreased off-target effect and improved on-target effects because of its targeting ability., Conclusion: The data acquired substantiates that HA-surface modified HMSNs functionalized with aptamers possess significant potential as a focused platform for efficient transportation of anticancer agents to neoplastic tissues.

In this study, a label-free aptasensor utilizing colorimetric properties was developed to detect Pb 2+ with high sensitivity. The approach involved applying modified aptamer which enhanced the oxidase-mimicking activity of MnO 2 nanoflowers. This innovative method provides an efficient means for monitoring Pb 2+ ions without requiring any labeling techniques. The fundamental principle of this aptasensor is based on the adsorption of a modified aptamer onto MnO 2 nanoflowers' surface, which in turn increases their affinity for chromogenic substrates and enhances their catalytic activity. The proposed aptasensor exploits the high sensitivity due to the extension of the aptamer sequence length by terminal deoxynucleotidyl transferase (TdT). Under optimum experimental conditions, the developed colorimetric aptasensor indicated a linear detection range from 4 to 80 nM with a limit of detection (LOD) of 1.4 nM. Moreover, the aptasensor successfully monitored Pb 2+ in the drinking water, milk and human serum samples. Henceforth, the colorimetric aptasensor exhibited in this study possesses several benefits such as uncomplicated operation, cost-effectiveness, label-free detection and remarkable sensitivity. Thus rendering it a suitable option for analyzing intricate samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this study, a targeted pH-sensitive polymersome incorporating doxorubicin (DOX) was manufactured implementing diblock copolymer of hyaluronic acid-b-pPoly (β-amino ester) (HA-PBAE). The hydrophilic DOX was loaded into the aqueous compartment of HA-PBAE polymersomal structure during nanoprecipitation process with 60 % ± 3.0 entrapment efficiency (EE%) and 5.3 % ± 0.2 loading content (LC%) while demonstrating spherical morphology with size of 196 ± 3.8 nm and PDI of 0.3. The prepared platform (DOX-HA-PBAE) illustrated accelerated DOX release in acidic pH 5.4, and showed significantly higher cytotoxicity and cellular internalization in comparison with free DOX against 4T1 cell line (CD44 positive cell). In contrast, no significant growth inhibition was observed in CHO cell line (CD44 negative cell). Furthermore, DOX-HA-PBAE platform displayed higher therapeutic efficacy, favorable tumor accumulation and lower systemic toxicity in comparison with free DOX based on obtained experimental data in ectopic 4T1 tumor model in BALB/c Female mice in terms of tumor growth rate, survival rate, body weight loss, ex vivo biodistribution and pathological evaluations. The obtained results demonstrated that DOX-HA-PBAE polymersomes have potential to be used in metastatic breast cancer therapy with promising characteristics in terms of tumor growth suppression and safety profile., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Here, a simple aptasensing approach is represented to sensitively detect ochratoxin A (OTA) as one of the most perilous mycotoxins with carcinogenic, nephrotoxic, teratogenic, and immunosuppressive sequels on human health. The aptasensor is based on the alteration in the orientational order of liquid crystal (LC) molecules at the surfactant-arranged interface. Homeotropic alignment of LCs is achieved by the interaction of the surfactant tail with LCs. By perturbing the alignment of LCs due to the electrostatic interaction of the aptamer strand with the surfactant head, a colorful polarized view of the aptasensor substrate is induced drastically. While OTA causes the re-orientation of LCs to a vertical state by forming an OTA-aptamer complex that induces darkness of the substrate. This study shows that the length of the aptamer strand impacts the efficiency of the aptasensor; longer strand results in the greater disruption of LCs, and therefore, increases the aptasensor sensitivity. Hence, the aptasensor can determine OTA in the linear concentration range of 0.1 fM-1 pM as low as 0.021 fM. The aptasensor is capable to monitor OTA in grape juice, coffee drink, corn, and human serum real samples. The proposed LC-based aptasensor provides a cost-effective, easy-to-carry, operator-independent, and user-friendly array with great potential to develop portable sensing gadgets for food quality control and health care monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

With the unpredictable risks on human health and ecological safety, tobramycin (TOB) as an extensively applied antibiotic has embraced global concern. Herein, a label-free fluorescent aptasensor was developed that opened up an innovative sensing strategy for monitoring trace TOB levels. Based on the rolling circle amplification (RCA) process, a giant DNA building was established by the catalytic action of T4 DNA ligase and Phi 29 DNA polymerase with the cooperation of the specific aptamer as a primer skeleton. By having the role of signal amplifier template, the RCA product with the G-quadruplex sequence duplications was decorated by a high number of the thioflavin T (ThT) fluorescent dyes. The aptasensor with good selectivity toward TOB achieved a detection limit as low as 150 pM. Thanks to its accurate target quantification, ease of operation, economic manufacture, as well as high potency for real-time and point-of-care testing, the represented aptasensor is superb for clinical application and food safety control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Due to the detrimental effects of cocaine on the human body such as organ damage, paranoia, immunodeficiency, cardiovascular disease, blood pressure, and stress, it is highly required to develop sensing approaches for its rapid and facile determination. Based on the signal enhancement capability of the UiO-66/AuNPs nanocomposite and acting as a capture agent, we designed a cost-effective fluorescent aptasensor for cocaine detection. The cocaine presence in the sample would cause a considerable escalation in the quenching of the fluorescence signal. The aptasensor achieved the linear response range over 0.5 μM-20 μM with a low detection limit of 0.178 μM. The selectivity of the designed aptasensing assay was successfully confirmed by examining several analgesic drugs. The aptasensor was employed for cocaine determination in human serum as the real samples. This method has a substantial benefit the for development of a low-cost and facile tool in medicine and forensic science., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Since gene therapy can regulate gene and protein expression directly, it has a great potential to prevent or treat a variety of genetic or acquired diseases through vaccines such as viral infections, cystic fibrosis, and cancer. Owing to their high efficacy, in vivo gene therapy trials are usually conducted intravenously, which is usually costly and invasive. There are several advantages to oral drug administration over intravenous injections, such as better patient compliance, ease of use, and lower cost. However, gene therapy is successful if the oligonucleotides can cross the cell membrane easily and reach the nucleus after the endosomal escape. In order to accomplish this task and deliver the cargo to the intended location, appropriate delivery systems should be introduced. This review summarizes oral delivery systems developed for effective gene delivery, vaccination, and treatment of various diseases. Studies have also shown that oral delivery approaches are potentially applicable to treat various diseases, especially inflammatory bowel disease, stomach, and colorectal cancers. Also, the current review provides an update overview on the development of non-viral and oral gene delivery techniques for gene therapy and vaccination purposes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A novel label-free and enzyme-free fluorescence aptasensing assay that uses Sybr Green I (SGI) as the signal indicator for the kanamycin determination was designed. An aptamer-complementary strand (Apt/CP) conjugate was formed, which provided the intercalation sites for SGI and, therefore, a considerable fluorescent signal. The introduction of the target led to the separation of Apt from CP due to the high affinity of Apt toward kanamycin. Hence, the suitable intercalation gaps reduced, which resulted in a decrease in the generated fluorescent signal. Under optimized conditions, a broad linear concentration range from 0.05 μM to 20 μM and a limit of detection of 11.76 nM were obtained, confirming the ability of the fabricated aptasensor for sensitive and specific kanamycin detection in real samples such as milk and human serum. The aptasensing method has the potential to be extensively employed in the food industry and veterinary science due to its simplicity, sensitivity, user-friendly, and capability of on-site detection of kanamycin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

As of today's requirement, developing cost-effective smart sensing tools with ultrahigh sensitivity for food safety insurance is of special importance. For this purpose, aptamer-based biosensors (aptasensors) powered by the superiorities of the recycling signal amplification strategies have been expanded especially. Target recycling supported by enzymes is an appealing approach for implementing signal amplification. As the supreme biocatalyst enzymes, exonucleases can inaugurate signal improvement by involving a single target in a process would result in appreciable repeating cycles of the cleavage of the phosphodiester bonds between the building blocks of the nucleic acid strands, and also, their terminals. Although there are diverse substances for catalyzing amplification strategies, including nanoparticles, carbon-based nanocomposites, and quantum dots (QDs), exonucleases are of superiority over them by simplifying the amplification process with no need for the complicated pre-treatment processes. The outstanding selectivity and great sensitivity of the aptasensors tuned by amplification potency of exonucleases nominate them as the promising sensing tools for label-free, ease-of-use, cost-effective, and real-time diagnosis of diverse targets. Here, we summarize the achievements and perspectives in the scientific branch of aptasensor design for the qualitative monitoring of diverse targets by cooperation of exonucleases with the conspicuous potential for the signal amplification. Finally, some results are expressed to provide a comprehensive viewpoint for developing novel nuclease-based aptasensors in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Mesenchymal stem cell membrane (MSCM)-coated biomimetic doxorubicin-loaded hollow gold nanoparticles were fabricated and decorated with MUC1 aptamer in order to provide smart theranostic platform. The prepared targeted nanoscale biomimetic platform was extensively characterized and evaluated in terms of selective delivery of DOX and CT-scan imaging. The fabricated system illustrated spherical morphology with 118 nm in diameter. Doxorubicin was loaded into the hollow gold nanoparticles through physical absorption technique with encapsulation efficiency and loading content of 77%±10 and 31%±4, respectively. The in vitro release profile demonstrated that the designed platform could respond to acidic environment, pH 5.5 and release 50% of the encapsulated doxorubicin during 48 h, while 14% of the encapsulated doxorubicin was released in physiological condition, pH 7.4 up to 48 h. The in vitro cytotoxicity experiments on 4T1 as MUC1 positive cell line illustrated that the targeted formulation could significantly increase mortality at 0.468 and 0.23 µg/ml of equivalent DOX concentration compared to non-targeted formulation while this cytotoxicity was not observed in CHO as MUC1 negative cell line. Furthermore, in vivo experiments showed high tumor accumulation of the targeted formulation even 24 h after intravenous injection which induced effective tumor growth suppression against 4T1 tumor bearing mice. On the other hand, existence of hollow gold in this platform provided CT scan imaging capability of the tumor tissue in 4T1 tumor bearing mice up to 24 h post-administration. The obtained results indicated that the designed paradigm are promising and safe theranostic system for fighting against metastatic breast cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this study, a sensitive fluorescent method is designed to detect tobramycin (TOB) drug applying a hybrid structure of three aptamer strands and SYBR Green I (SGI) fluorescent dye as the bioreceptor segment and signal indicator, respectively. The preferential binding of the aptamers to TOB resulted in the collapse of the hybridized aptamer skeleton to the single strands. So, the intercalation of SGI molecules reduced that quenched the fluorescence response. The aptasensing assay provided the superior target specificity with a detection limit (LOD) of 0.153 pM and a wide linear dynamic range over 0.5 pM-300 μM. The aptasensor could successfully quantify TOB in human serum samples. The tag-free sensor with the remarkable advantages of simplicity, easy-to-use, cost-effectiveness, and high sensitivity is superior to be applicable for clinical samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: We evaluated the DNA nanocarriers synthesized by rolling circle amplification (RCA), composed of multiple repeats of AS1411 and FOXM1 aptamers for targeted epirubicin delivery to breast cancer cells., Methods: Agarose gel electrophoresis and scanning electron microscopy were used to nanostructure characterizing. Drug loading and drug release were determined by fluorometry. Cytotoxicity comparison by MTT assay was applied among epirubicin, nanoparticle, and complex (nanoparticle carrying epirubicin) in L929 (normal murine fibroblast) and 4T1 (murine mammary carcinoma) cells. Cellular epirubicin internalization was assessed by flow cytometry and fluorescence imaging. In vivo studies in 4T1 tumor-bearing BALB/c mice were conducted by monitoring tumor volume, mouse weight, and mortality rate and measuring the accumulated epirubicin in organs., Results: The negatively charged nanoparticles were under 200 nm and stable. Fifty microliters of 6 μM epirubicin was loaded in 50 μL nanoparticle. Epirubicin release at acidic pH was more. Complex compared with epirubicin, had more entry and cytotoxicity in target cells ( p value ≤.01), higher therapeutic effect ( p value ≤.001), and tumor drug accumulation., Conclusion: The poly-aptamer nanocarriers have the characteristics of being safe, stable, efficient epirubicin loading, pH-dependent drug release, and tumor-targeting ability in vitro and in vivo .

Gold nanorods (GNRs/AuNRs) are a group of gold nanoparticles which their simple surface chemistry allows for various surface modifications, providing the possibility of using them in the fabrication of biocompatible and functional nano-agents for cancer therapy. AuNRs, moreover, exhibit a maximum absorption of longitudinal localized surface plasmon resonance (LSPR) in the near-infrared (NIR) region which overlaps with NIR bio-tissue 'window' suggesting that they are proper tools for thermal ablation of cancer cells. AuNRs can be used for induction of mono or combination therapies by administering various therapeutic approaches such as photothermal therapy (PTT), photodynamic therapy (PDT), chemotherapy (CT), radiotherapy (RT), and gene therapy (GT). In this review, anticancer therapeutic capacities of AuNRs along with different surface modifications are summarized comprehensively. The roles of AuNRs in fabrication of various nano-constructs are also discussed., Competing Interests: Declaration of Competing Interest There is no conflict of interest about this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Peptosomes, as a vesicular polypeptide-based system and a versatile carrier for co-delivery of hydrophilic and hydrophobic materials, provide great delivery opportunities due to the intrinsic biocompatibility and biodegradability of the polypeptides backbone. In the current study, a novel poly(L-glutamic acid)-block-polylactic acid di-block copolymer (PGA-PLA) was synthesized in two steps. Firstly, γ-benzyl L-glutamate-N-carboxy anhydride (BLG-NCA) and 3,6-dimethyl-1,4-dioxane-2,5-dione were polymerized using N-hexylamine and benzyl alcohol as initiators to produce poly(γ-benzyl L-glutamate (PBLG) and polylactic acid. Then, PBLG was deprotected to produce PGA. Secondly, PGA was conjugated to the benzyl-PLGA to fabricate PGA-PLA diblock copolymer. The synthesized diblock copolymer was used for the encapsulation of doxorubicin, as hydrophilic anticancer and ultra-small superparamagnetic iron oxide nanoparticles (USPIONs) as hydrophobic contrast agent within aqueous core and bilayer of vesicular peptosome, respectively via double emulsion method. The prepared peptosomes (Pep@USPIONs-DOX) controlled the release of DOX (<15 % of the encapsulated DOX release up to 240 h of incubation at the physiological conditions) while increasing the stability and solubility of the hydrophobic USPIONs. Then, AS1411 DNA aptamer was decorated on the surface of the PGA-PLA peptosomes (Apt-Pep@USPIONs-DOX). The prepared targeted and non-targeted platforms showed spherical morphology with hydrodynamic sizes of 265 ± 52 and 229 ± 44 nm respectively. In vitro cellular cytotoxicity and cellular uptake were studied in nucleolin positive (4T1) and nucleolin negative (CHO) cell lines. Cellular uptake of the targeted formulation was greater than that of non-targeted peptosome, while cellular internalization of these peptosomes was identical in CHO cells. Moreover, targeted peptosomes showed greater toxicity than non-targeted peptosome in 4T1 cell line. The prepared theranostic targeted peptosomes demonstrated improved capability in terms of survival rate, biodistribution, tumor suppression efficiency, and MR imaging in the 4T1 tumor-bearing mice., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: A targeted delivery platform was prepared to co-deliver both doxorubicin (Dox) as an anticancer drug and FOXM1 aptamer as a therapeutic substance to breast cancer cells (4T1 and MCF-7) to reduce Dox side effects and increase its therapeutic efficacy. The targeted system (AuNPs-AFPA) consisted of FOXM1 aptamer, AS1411 aptamer (targeting oligonucleotide), ATP aptamer, and gold nanoparticles (AuNPs) as a carrier., Materials and Methods: AuNPs were synthesized by reduction of HAuCl4. Next, after pegylation of ATP aptamer, FOXM1 aptamer-PEGylated ATP aptamer conjugate (FPA) was prepared. Then, the AS1411 aptamer and FPA were exposed to the AuNPs surface through their thiol groups. Subsequently, Dox was loaded into the complex to form a targeted therapeutic complex., Results: The data of the MTT assay displayed that the targeted complex could remarkably reduce cell viability rate in target cells due to the overexpression of nucleolin on their cell membranes compared to nontarget cells, showing the targeting ability of AuNPs-AFPA-Dox. The in vivo antitumor effect confirmed that AuNPs-AFPA-Dox was capable of remarkably diminishing tumor growth relative to the free Dox in mice bearing 4T1 tumor cells., Conclusion: The results confirmed that the targeted system improved the therapeutic effect by loading high amounts of Dox alongside the presence of the therapeutic effect of FOXM1 aptamer. Finally, it can be concluded that AuNPs-AFPA-Dox by enhancing antitumor effectiveness and reducing toxicity toward non-target cells, can be used potentially as an effective strategy for the treatment of breast cancer., Competing Interests: There are no conflicts of interest in this article.

Objectives: Designing and fabrication of theranostic systems based on nanoscale gaseous vesicular systems, named nanobubbles (NBs), attracted enormous interest in recent years. Biomimetic vesicular platform (V-RBC-M) can improve the pharmacokinetics of the prepared platform due to augmented circulation half-life, desirable biodegradability and biocompatibility and reduced immunogenicity., Methods: V-RBC-M were used for the encapsulation of lipophilic camptothecin (CPT) in the bilayer of vesicles through top-down method, followed by filling the core of V-RBC-M with inert SF6 gas to fabricate NBs with ultrasonic contrast enhancement capability (SF6-NB-CPT). In the next step, targeted NBs were formed via decoration of MUC1 aptamer on the surface of NBs (Apt-SF6-NB-CPT)., Results: The designed bio-NBs indicated high encapsulation efficiency and the sustained release of CPT at pH 7.4. In vitro study demonstrated higher cellular uptake and cytotoxicity of Apt-SF6-NB-CPT compared to SF6-NB-CPT in MUC1-overexpressing cells (C26). In vivo antitumor efficacy of the prepared NBs on C26 bearing BALB/c mice showed greater therapeutic efficacy and survival rate for Apt-SF6-NB-CPT. In this regard, SF6-NB-CPT showed 58% tumor growth suppression while Apt-SF6-NB-CPT system provided 95% tumor growth suppression. Furthermore, echogenic capability of SF6-NB-CPT was demonstrated through in vitro and in vivo ultrasonic imaging., Conclusions: Our finding demonstrated that the prepared targeted NBs are a promising theranostic platform with effective therapeutic and diagnotic potentials.

Developed herein is an aptasensing array based on liquid crystal (LC) for monitoring of tobramycin (TOB) antibiotic. The direction of LC molecules from vertical to a random status was induced by the conformational changes of the specific aptamer due to its selective interaction with the target. The dark view of the aptasensing platform changed to colorful through observation by a polarized light microscope that clarifies the TOB presence. The aptasensor is especially able to determine TOB in the linear concentration range of 0.005-600 pM with a limit of detection (LOD) as 0.0021 pM. The TOB values can be determined successfully in the milk and chicken egg samples that highlights the potential applicability of the designed aptasensor. The proposed sensing approach is facile, operator-independent, label-free, and ultra-sensitive, making it novel for developing real-time portable sensing devices for future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Herein, we presented a novel DOX-loaded multi-storey DNA nanostructure, including AS1411 aptamer as a targeting agent for treatment of target cells (MCF-7 and 4T1). Gel retardation test and fluorometric analysis were used to examine the construction of DNA nanostructure and loading of DOX in the complex. At pH 5.5 and 7.4, the release patterns of DOX from the prepared formulation were studied. Cell viability test was conducted to analyse the cell cytotoxicity ability of the DOX loaded multi-storey DNA nanostructure compared to free DOX in 4T1, MCF-7 (target) and CHO cells (non-target). Flow cytometry analysis was used to examine the DOX-loaded DNA nanostructure internalisation. Finally, the developed DOX-loaded multi-storey DNA nanostructure was tested in vivo to see if it could prevent tumour growth. The drug was released from the nanocomplex in a pH-related process (higher release in acidic pH compared to neutral pH). According to MTT assay, DOX-loaded DNA nanostructure damaged nucleolin positive cells while not significantly affecting nucleolin negative cells. The formulation was efficaciously internalised into target cells (4T1 and MCF-7), but not into non-target ones. Moreover, DOX-loaded DNA nanostructure can restrict tumour growth, increase survival rate, and accumulate significantly more in the tumour site than free DOX.

The importance of the early-stage diagnosis and in situ monitoring of lesion regions and transportation of bioactive molecules has a pivotal effect on successful treatment, reducing side effects, and increasing the chances of survival in the case of serious diseases such as cancer. This strongly depends on the development of contrast agents and biomarkers together with the appropriate use of bioimaging techniques. Because of their exceptionally high surface area and porosity, nanoscale metal-organic frameworks (NMOFs) have been the subject of numerous studies in the biomedical domain as drug carriers, diagnostic and therapeutic agents, and biosensors. This review provides a summary of the recent advancements in the use of MOFs as nanoscale platforms for biomedical imaging via magnetic resonance (MR) imaging, computed tomography (CT), single-photon emission computed tomography (SPECT), fluorescence (FL) imaging, positron emission tomography (PET), photoacoustic (PA) imaging, and photothermal (PT) imaging modalities. Initially, we describe the principles of a specific imaging technique in each section, and then present the recent reports on MOFs for monomodal and multimodal imaging and the following information: (i) how to synthesize MOFs and modify their surface and (ii) their utilization in bioimaging or theranostic applications.

On-site and real-time clinical monitoring have been progressed dramatically by integrating biosensor science with portable digital electronic technology. Clustered regularly interspaced short palindromic repeats (CRISPR) with association of RNA-guided nucleases (CrRNA-Cas enzymes) have achieved novel CRISPR/Cas biosensing science as a promising revolutionized diagnostic technology for portable and on-site healthcare monitoring and diagnostics. Among several available CRISPR/Cas systems, CRISPR/Cas12a and CRISPR/Cas13a conjugates are utilized broadly in biosensor design, because of their capability to cleave both target and non-target sequences. With the advantages of portability, cost-effectiveness, facile operation, high durability, and reproducibility, CRISPR/Cas-based biosensing techniques are a perfect choice for designing ultra-sensitive point-of-care diagnostic devices with amplified response signals. In the present review, we summarize the advances in the CRISPR/Cas-based biosensors with the focus on healthcare and diagnostic purposes. The cooperation of nanomaterial engineering with CRISPR/Cas biosensors is also represented to attain a promising viewpoint for offering novel user-friendly test kits for announcing ultra-low levels of diverse targets in the future., (Copyright © 2022 Elsevier B.V. All rights reserved.)