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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.)

Amphiphilic block copolymers are common materials used for the fabrication of various nanostructures with biomedical applications including nanocapsules, nanospheres, micelles and polymeric vesicles. According to the literature, polymersomes have several advantages compared to other nanostructures used as drug delivery systems comprising better stability, facile synthesis, prolonged circulation time, and passive/active targeting capability. Various types of nanoparticles are formed by varying the ratio of the hydrophobic/hydrophilic blocks. Changing hydrophobic/hydrophilic ratio of amphiphilic block copolymers has an impact on the structural characteristics of polymers such as changing molecular weight and surface functionalization of the block copolymer. Thus, polymerization strategies are an important factor that influences polymersomes quality. In this review, different polymerization strategies for the synthesis of block copolymers applied in polymersomes formation, are described., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Targeted therapy and early accurate detection of malignant lesions are essential for the effectiveness of treatment and prognosis in cancer patients. The development of gaseous system as a versatile platform for the fabricated nanobubbles, has attracted much interest in improving the efficacy of ultrasound therapeutic, diagnostic, and theranostic platforms. Nano-sized bubble, as an ultrasound contrast agent, with spherical gas-filled structures exhibited contrast enhancement capability due to their inherent EPR effect. Additionally, nanobubbles exhibited good stability with extended retention time in the blood stream. The current review summarized various nanobubbles and discussed about the crucial parameters affecting the stability of ultrafine bubbles. Furthermore, therapeutic and theranostic gaseous systems for fighting against cancer were described., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In spite of huge developments in cancer treatment, versatile combinational formulations of different chemotherapeutic agents to enhance anticancer activity while reducing systemic toxicity still remains a challenge. In this regard, in the current study, an amphiphilic hyaluronic acid-b-polycaprolactone diblock copolymer was synthesized using "click chemistry". The synthesized copolymer was self-assembled to form polymersomal structures for co-encapsulation of hydrophilic doxorubicin (DOX) and hydrophobic camptothecin (CPT) in their interior aqueous compartment and their bilayer, respectively with 1:10 and 1:1 ratios. The prepared polymersomal combinational formulation surrounded by hyaluronic acid brush as hydrophilic segment, could provide active targeting of the system against CD44 marker expressed on the surface of cancerous cells. The hyaluronic acid shell could also provide flexible chemistry for the conjugation of therapeutic FOXM1-specific DNA aptamer (Forkhead Box M1; against transcription factor FOXM1) on the surface of polymersomes in order to further suppress cancerous cell proliferation. The obtained results demonstrated that the prepared co-formulation provided sustained, controlled release of the entrapped drugs during 200 h. In vitro cytotoxicity experiments on non-small cell lung cancer, A549 and SK-MES-1 cell lines, demonstrated that the co-formulation of DOX and CPT provided synergistic effect and significantly higher cytotoxicity in comparison with free drugs. The cytotoxicity experiment also indicated that the aptamer conjugation on the co-formulations surface could significantly increase the cytotoxicity and induce apoptosis in combination therapy on both A549 and SK-MES-1 cell lines while aptamer-conjugated blank NPs did not show any cytotoxicity which emphasizes on the sensitization capability of the FOXM1 DNA aptamer against non-small cell lung cancer. Furthermore, it was shown that the co-formulation with or without aptamer renders the formulation specific tumor accumulation in vivo 24 h post-administration, assisting the combination synergy observed in vitro to be translated to in vivo antitumor efficacy. This combinatorial delivery platform strongly offers a novel approach for the synergistic controlled transportation of several chemotherapeutics for the treatment of non-small cell lung cancer., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The progress in advanced materials using nanoscale components can be conducted by an innovative idea involving combining nanotechnology approaches with supramolecular chemistry. This concept which is called self-assembly, is employed for formation of nanoscale self-assembled architectures with desirable properties. Self-assembly has emerged as a potent procedure for controlling the structure and characteristics of ensembles. Among self-assembled structures, polymersomes have revealed prodigious potential in drug delivery and development of smart nanomedicine due to their morphological similarities to cellular membranes and viral capsids. Moreover, their functional, tunable and stable membrane render them more advantageous to their lipid counter parts. Polymersomes have been used as different therapeutic carriers as drugs and imaging agents, as well as nanoreactors and artificial organelles. Here we review different basis of self-assembling polymersomes and their properties, the synthesis of various amphiphilic copolymers for vesicles preparation and potential applications of smart controlled release vesicles., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Nanogels as a versatile vehicle for doxorubicin have attracted great attention during the last decade. Since a nanogel composite device transport encapsulated drugs to the site of action and release them in a desirable time-frame, it could provide higher therapeutic effect. By implementation of different polymers, polymer/inorganic NPs and various crosslinking chemistry, it is possible to fabricate novel composite nanogel systems with favorable characteristics such as smart intelligent systems or multipurpose platforms. Due to high stability, good drug loading capacity for hydrophobic and hydrophilic agents, nanogels introduce great opportunity in pharmaceutical innovations. Composite nanogels show capability in gene, drug and diagnostic agents' delivery while providing an ideal platform for theranostic purposes as multifunctional systems. Doxorubicin as an anticancer agent is widely used against numerous cancers. Due to high systemic toxicity of doxorubicin, there is still need for its safe and specific delivery to the site of action. In this regard, so many efforts have been put in by the researchers for preparation of different nanogel formulations of doxorubicin in order to produce more efficient formulations. This review focuses on design, fabrication, advantages and disadvantages of composite nanogel-based doxorubicin formulations., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Accumulation at tumor tissue without any damage to healthy normal tissues is an ultimate goal in cancer therapy. Despite many efforts in the field of cancer therapy, this disease remains as the major reason of mortality all over the world. Gene therapy has introduced great opportunity to fight against cancer disease. It should be noted that still some obstacles limit clinical application of gene delivery approach, which have to be overcome for efficient transportation of therapeutic gene to the site of action. In this regard, carbon nanomaterials and their unique physical and chemical properties such as their capability of DNA protection have attracted much attention in the field of nanomedicine and non-viral carriers for therapeutic genes. Although, negligible solubility of carbon nanomaterials in biological environments has limited their biomedical application but their structural characteristics facilitate their chemical modifications thereby overcoming their solubility problem. Moreover, hybridization of modified carbon materials with different polymers provides more biocompatible and capable systems for gene delivery purposes. In the current review, we summarized hybrid carbon-based materials as non-viral carriers for gene delivery., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recent technological approaches in drug delivery have attracted scientist interest for improving therapeutic index of medicines and drug compliance. One of the powerful strategies to control the transportation of drugs is implementation of intelligent stimuli-responsive drug delivery system (DDS). In this regard, tumor tissues with unique characteristics including leaky vasculature and diverse enzyme expression profiles facilitate the development of efficient enzyme-responsive nanoscale delivery systems. Based on the stimuli nature (physical, chemical and biological), these systems can be categorized into three groups according to the nature of trigger initiating the drug release. Enzymes are substantial constituents of the biotechnology toolbox offering promising capabilities and ideal characteristics to accelerate chemical reactions. Nanoparticles which have the ability to trigger their cargo release in the presence of specific enzymes are fabricated implementing fascinating physico-chemical properties of different materials in a nanoscale dimension. In order to reduce the adverse effects of the therapeutic agents, nanocarriers can be utilized and modified with enzyme-labile linkages to provide on-demand enzyme-responsive drug release. In the current review, we give an overview of drug delivery systems which can deliver drugs to the tumor microenvironment and initiate the drug release in response to specific enzymes highly expressed in particular tumor tissues. This strategy offers a versatile platform for intelligent drug release at the site of action., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Mesenchymal stem cell-derived exosome is a safe and effective delivery platform with a potential capacity to exert immunomodulation effect and peripheral tolerance toward auto-reactive cells via bearing regulatory and tolerogenic molecules. Inflammation and neurodegeneration are the clinical manifestation of multiple sclerosis (MS). In order to fight against MS, the efficient choices are the ones, which prevent inflammation and induce remyelination. In this regard, the previously reported LJM-3064 aptamer which showed considerable affinity toward myelin and demonstrated remyelination induction was employed as both targeting ligand and therapeutic agent. Thus, in the current study, the carboxylic acid-functionalized LJM-3064 aptamer was covalently conjugated to the amine groups on the exosome surface through EDC/NHS chemistry. The obtained results showed that the aptamer-exosome bioconjugate could promote the proliferation of oligodendroglia cell line (OLN93) in vitro. Moreover, in vivo administration of the prepared aptamer-exosome bioconjugate in female C57BL/6 mice as a prophylactic measure produced a robust suppression of inflammatory response as well as lowered demyelination lesion region in CNS, resulting in reduced in vivo severity of the disease. The prepared platform employing exosome-based nanomedicine as a novel approach for managing MS would hopefully pave the way to introduce a versatile approach toward an effective clinical reality., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Therapeutic peptides are attracting increasing attention for biomedical applications. Peptides present promising opportunities in targeted drug delivery due to their high specificity, selectivity, small dimensions, ease of modification, and high biocompatibility. During the last decade, the potential of peptides as therapeutics or targeting ligands has been boomed in nanotechnology and cancer research. This review summarizes various peptides as therapeutics and targeting ligands in cancer therapy. At first, two categories of tumor homing and cell penetrating peptides (CPPs) are introduced and then we will discuss the modification of CPPs. Then various types of tumor targeting peptides and their applications in cancer research are represented., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In the current study, thermoresponsive poly(N-isopropylacrylamide)-doxorubicin (PNIPAM-DOX) hydrogel was synthesized and loaded into pH-responsive poly ethylene glycol)-2,4,6- trimethoxy benzylidene pentaerythritol carbonate (PEG-PTMBPEC) polymersomes in order to fabricate a smart thermo-pH stimuli responsive drug delivery system. Thermo-pH responsive polymersomal formulation of DOX revealed average size of 170 ± 11.2 nm. The prepared system was loaded with PNIPAM-DOX conjugate with encapsulation efficiency of 30.80%. The in vivo release evaluation demonstrated that the DOX release from polymersomal formulation was pH-dependent, i.e. significantly faster drug release at pH 5.5and 6.5 compared to physiological pH. On the other hand, the drug release rate was significantly decreased at 37 °C due to the gelation of PNIPAM-DOX conjugate in the interior compartment of the pH-responsive polymersomes. The in vivo anti-tumor efficiency of the prepared polymersomal formulation of DOX was evaluated implementing C26 tumor-bearing mice after either intravenous (i.v.) or intratumoral (i.t.) single dose injection. The obtained results demonstrated that the prepared system significantly inhibited tumor growth rate in mice receiving single dose via either intravenous or intratumoral injection in comparison with free DOX-treatment group. Furthermore, treatment with polymersomal formulation did not cause any systematic toxicity in terms of pathological alteration of vital organs, survival rate and body weight loss. The prepared smart hydrosomal formulation significantly increased the blood half life time of drug and modified the biodistribution and pharmacokinetic parameters of formulated DOX. In this regard, thermo-pH-dual-stimuli responsive hydrosomal formulation represent a novel approach in nanomedicine development for effective cancer therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Silica hybrid materials play an important role in improvement of novel progressive functional nanomaterials. Study in silica hybrid functional materials is supported by growing interest in providing intelligent materials that combine best of the inorganic silica structure along with organic or biological realms. Hybrid silica materials do not only provide fantastic opportunities for the design of novel materials for research but their represented unique properties open versatile applications specifically in nanomedicine since it was recognized by US FDA as a safe material for human trials. By combining various materials with different characteristics along with silica NPs as building blocks, silica-based hybrid vehicles were developed. In this regard, silica-based hybrid materials have shown great capabilities as unique carriers for bioimaging and/or drug delivery purposes. In the aforementioned hybrid systems, silica was preferred as a main building block of the hybrid structure, which is easily functionalized with different materials, bio-molecules and targeting ligands while providing biocompatibility for the system. This review will cover a full description of different hybrids of silica nanoparticles including silica-polymer, silica-protein, silica-peptide, silica-nucleic acid, silica-gold, silica-quantum dot, and silica-magnetic nanoparticles and their applications as therapeutic or imaging systems., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Treatment of critical-size bone defects is a major medical challenge since neither the bone tissue can regenerate nor current regenerative approaches are effective. Emerging progresses in the field of nanotechnology have resulted in the development of new materials, scaffolds and drug delivery strategies to improve or restore the damaged tissues. The current article reviews promising nanomaterials and emerging micro/nano fabrication techniques for targeted delivery of biomolecules for bone tissue regeneration. In addition, recent advances in fabrication of bone graft substitutes with similar properties to normal tissue along with a brief summary of current commercialized bone grafts have been discussed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Gold nanoparticles (AuNPs) have attracted great attention in biomedical fields due to their unique properties. However, there are few reports on clinical trial of these nanoparticles. In vivo, AuNPs face complex biological fluids containing abundant proteins, which challenge the prediction of their fate that is known as "bio-identity". These proteins attach onto the AuNPs surface forming protein corona that makes the first step of nano-bio interface and dictates the subsequent AuNPs fate. Protein corona formation even stealth active targeting effect of AuNPs. Manipulating the protein corona identity based on the researcher goal is the way to employ corona to achieve maximum effect in therapy or other applications. In this review, we provide details on the biological identity of AuNPs under various environmental- and/or physiological conditions. We also highlight how the particular corona can direct the biodistribution of AuNPs. We further discuss the strategies available for controlling or reducing corona formation on AuNPs surface and achieving desired effects using AuNPs in vivo by engineering protein corona on their surface., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Due to the severe cardiotoxicity of doxorubicin, its usage is limited. This shortcoming could be overcome by modifying pharmacokinetics of the drugs via preparation of various nanoplatforms. Doxil, a well-known FDA-approved nanoplatform of doxorubicin as antineoplastic agent, is frequently used in clinics in order to reduce cardiotoxicity of doxorubicin. Since Doxil shows some shortcomings in clinics including hand and food syndrome and very slow release pattern thus, there is a demand for the development and preparation of new doxorubicin nanoformulation with fewer side effects. The new formulation of the doxorubicin, synthesized previously by our group was extensively examined in the current study. This new formulation is doxorubicin encapsulated in PEG-PLGA polymersomes (PolyDOX). The main aim of the study was to compare the distribution and treatment efficacy of a new doxorubicin-polymersomal formulation (PolyDOX) with regular liposomal formulation (Doxil-mimic) in murine colon adenocarcinoma model. Additionally, the pathological, hematological changes, pharmacodynamics, biodistribution, tolerated dose and survival rate in vivo were evaluated and compared. Murine colon cancer model was induced by subcutaneous inoculation of BALB/c mice with C26 cells. Afterwards, either Doxil-mimic or PolyDOX was administered intravenously. The obtained results from biodistribution study showed a remarkable difference in the distribution of drugs in murine organs. In this regard, Doxil-mimic exhibited prolonged (48h) presence within liver tissues while PolyDOX preferentially accumulate in tumor and the presence in liver 48h post-treatment was significantly lower than that of Doxil-mimic. Obtained results demonstrated comparable final length of life for mice receiving either Doxil-mimic or PolyDOX formulations whereas tolerated dose of mice receiving Doxil-mimic was remarkably higher than those receiving PolyDOX. Therapeutic efficacy of formulation in term of tumor growth rate after one injection of formulations (5mg/kg, 10mg/kg or 15mg/kg) demonstrated better efficacy at lower dose for PolyDOX. Analysis of Kaplan Meier curve was in favor of both formulations in their treatment-dose. Pathological and hematological surveys of mice treated with both formulations did not show considerable difference except for a small atrophy in liver observed after successive administration of Doxil-mimic. It could be concluded that PolyDOX can potentially limit off-site effects of Doxil due to its biodegradability and sustained release properties while it exhibited favorable safety profile comparable to Doxil., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In this study, a tumor-targeted, docetaxel encapsulated dextran-poly lactide-co-glycolide (DEX-PLGA) polymersomes was fabricated for breast cancer chemotherapy. To attain active cancer targeting, docetaxel encapsulated polymersomes was conjugated with folate for folate receptor guided delivery which is overexpressed in various cancer cells including breast adenocarcinoma. Docetaxel was encapsulated in the bilayer of DEX-PLGA or folate-conjugated DEX-PLGA (FA-DEX-PLGA) polymersomes via nanoprecipitation method in order to provide the controlled drug release. The size of polymersomes obtained were 178.53±2.5nm and offered drug encapsulation efficiency and loading content of 78.85±3.81% and 9.32±0.27, respectively. The data demonstrate that the prepared polymersome formulations sustained docetaxel release for a period of 6days. Cellular uptake study and MTT assay showed that the developed folate-targeted docetaxel-loaded polymersomes had higher cytotoxicity than non-targeted ones as well as free form of drug and was accumulated in 4T1 and MCF-7 cells in vitro. The in vivo tumor inhibitory effect of folate-conjugated docetaxel-loaded DEX-PLGA polymersomes (FA-DEX-PLGA-DTX-NPs) demonstrated an increased therapeutic potency of targeted formulation over both non-targeted (DEX-PLGA-DTX-NPs) and free drug. The represented data reveal that the prepared targeted drug delivery system was able to control the docetaxel release, and also enhance the antitumor potency of docetaxel. This study may open new direction for preparation of folate receptor targeted polymersomes based on DEX-PLGA copolymers for translational purposes., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Insulin is the first line therapy in type 1 diabetes and usually patients suffer from three or more daily insulin injections. It is obvious that patient compliance can be improved greatly if insulin could be formulated in an oral dosage form. In the current study, polymersomes based on amphiphilic copolymers of dextran (DEX)5000-poly(lactic-co-glycolic acid) (PLGA)13,000 and DEX25000-PLGA48000 were synthesized and used for the encapsulation of insulin. The polymersomes were prepared using a modified direct hydration method by blending an aqueous solution of insulin with DEX-PLGA copolymers at room temperature. The in vitro insulin release through the nanopolymersomal system was studied in HCl 0.1N (pH1.2) and phosphate buffered saline (pH7.4). The results demonstrated that the average insulin encapsulation efficiency was >90%. The in vitro release experiment demonstrated that while insulin release in the simulated gastric condition was negligible, a significant amount of insulin was released in the simulated intestinal condition. According to the results of a circular dichroism test, secondary and tertiary structures of the released insulin were identical to that of standard insulin. Permeability studies across MDCK cells showed that permeability levels after 240 min were 16.89 ± 0.39% with DEX5000-PLGA13000 and 9.34 ± 0.79% with DEX25000-PLGA48000, indicating a noticeable increase compared with free insulin. Significant hypoglycemic effects in the in vivo diabetic rat model revealed the efficacy of the DEX-PLGA-based polymersomes as oral insulin carriers. Thus, insulin-loaded, self-assembled DEX-PLGA polymersomes showed promising in vitro and in vivo efficiency and can be considered as a potential oral insulin carrier system., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Targeted, disease-specific delivery of therapeutic nanoparticles shows wonderful promise for transmitting highly cytotoxic anti-cancer agents. Using the reaction of non-small cell lung cancer (SK-MES-1 and A549 cell lines) as representative of other cancer types', the present study examines the effects of EpCAM-fluoropyrimidine RNA aptamer-decorated, DOX-loaded, PLGA-b-PEG nanopolymersomes that bond specifically to the extracellular domain of epithelial-cell adhesion molecules. Results demonstrate that EpCAM aptamer-conjugated DOX-NPs (Apt-DOX-NP) significantly enhance cellular nanoparticle uptake in SK-MES-1 and A549 cell lines and increase the cytotoxicity of the DOX payload as compared with non-targeted DOX-NP (P<0.05). Additionally, Apt-DOX-NP exhibits greater tumor inhibition in nude mice bearing SK-MES-1 non-small cell lung-cancer xenografts and reduces toxicity, as determined by loss of body weight, cardiac histopathology and animal survival rate in vivo. After a single intravenous injection of Apt-DOX-NP and DOX-NPs, tumor volume decreased 60.9% and 31.4%, respectively, in SK-MES-1-xenograft nude mice compared with members of a saline-injected control group. This study proves the potential utility of Apt-DOX-NP for therapeutic application in non-small cell lung cancer. In the future, EpCAM-targeted therapies might play a key role in treating non-small cell lung cancer, the most common type of lung cancer., (Copyright © 2015 Elsevier B.V. All rights reserved.)