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The regulation of intracellular ionic homeostasis to trigger antigen-specific immune responses has attracted extensive interest in tumor therapy. In this study, we developed a dual-pathway nanoreactor, Au-Cu 2-x Se@ZIF-8@P18 NPs (ACS-Z-P NPs), which targets danger-associated molecular patterns (DAMPs) and releases Zn2+ and reactive oxygen species (ROS) within the tumor microenvironment (TME). Zn2+ released from the metal–organic frameworks (MOFs) was deposited in the cytoplasm, leading to aberrant transcription levels of intracellular zinc-regulated proteins and DNA damage, thereby inducing pyroptosis and immunogenic cell death (ICD) dependent on caspase1/gasdermin D (GSDMD) pathway. Furthermore, upon laser irradiation, ACS-Z-P NPs could break through the limitations of inherent defects of immunosuppression in TME, enhance ROS generation through a Fenton-like reaction cascade, which subsequently triggered the activation of inflammatory vesicles and the release of damage-associated molecular patterns (DAMPs). This cascade effect led to the amplification of pyroptosis and immunogenic cell death (ICD), thereby remodeling the immunosuppressed TME. Consequently, this process improved dendritic cell (DC) antigen presentation and augmented anti-tumor T-cell responses, effectively initiating antigen-specific immune responses and further enhancing pyroptosis and ICD. This study explores the therapeutic properties of these mechanisms in detail. The synthesized Au-Cu 2-x Se@ZIF-8@P18 nanoparticles (ACS-Z-Ps) can effectively enhance the bodyʼs immune response by regulating zinc ion levels within cells. This regulation leads to abnormal levels of zinc-regulated protein transcription and DNA damage, which induces cellular pyroptosis. As a result, antigen presentation to dendritic cells (DCs) is improved, and anti-tumor T-cell responses are enhanced. The ACS-Z-P NPs overcome the limitations of ROS deficiency and immunosuppression in the tumor microenvironment by using H 2 O 2 in the tumor microenvironment through a Fenton-like reaction. This leads to an increased production of ROS and O 2 , remodeling of the immunosuppressed tumor microenvironment, and enhanced induction of cell pyroptosis and immunogenic cell death. ACS-Z-P NPs targeted B16 cells using the photosensitizer P18 in combination with PDT treatment. This approach significantly inhibited the proliferation of B16 cells and effectively inhibited tumor growth. [Display omitted] [ABSTRACT FROM AUTHOR]

This study reveals the pH-responsive behavior of collagen hydrogels prepared using ultraviolet (UV) irradiation with riboflavin as a photosensitizer. By varying the UV exposure time, we modulated the crosslinking density, thereby influencing the mechanical properties and pH responsiveness. Rheological analysis confirmed successful network formation, whereas swelling studies revealed significant pH-dependent behavior, with maximum swelling at a pH of four and minimal swelling above a pH of six, demonstrating partial reversibility over multiple pH cycles. Mechanical testing showed a pH-dependent elastic modulus, which increased 10 fold from a pH of 6 to 10. Fibroblast proliferation assays confirmed the biocompatibility of the hydrogels, with cell growth positively correlating with the UV exposure time. This research demonstrates the potential of UV-crosslinked collagen hydrogels in biomedical applications, such as tissue engineering and drug delivery, where pH responsiveness is essential. [ABSTRACT FROM AUTHOR]

This review covers the progress in recent years on pH-responsive polymers integrated with natural colorants. The classification of various natural colorants, including anthocyanin, curcumin, and alizarin, and the pigments' structural changes at different pH are introduced. Subsequently, the latest research in substrates for immobilizing natural colorants is discussed. Moreover, their applications on wound dressing for bacterial infections monitoring, smart package for food quality monitoring, and textile dyeing, are outlined. Finally, this study was summarized by emphasizing the current challenges and future opportunities in the field of pH-responsive polymers. [ABSTRACT FROM AUTHOR]

The combination of magnetic resonance and fluorescence imaging in dual‐modality imaging not only resolves the limitations of conventional single molecular imaging techniques in terms of specificity, sensitivity, and resolution but also expands the possibilities of molecular imaging techniques in diagnostics and therapeutic monitoring. Herein, a novel pH‐responsive magnetic resonance/near‐infrared fluorescence (MR/NIRF) nanoprobe (MnO2@BSA‐Cy5.5) was successfully prepared by biomineralizing manganese dioxide (MnO2) with bovine serum albumin (BSA) while coupling fluorescent dye Cy5.5 for precise tumor detection and visualization. The synthesized MnO2@BSA‐Cy5.5 nanoprobes were spherical particles of approximately 22.62 ± 3.31 nm in size, and their relaxation rates and T1 imaging signals were activated‐enhanced in an acidic environment. Cytotoxicity assay and hematoxylin and eosin staining demonstrated that MnO2@BSA‐Cy5.5 had low cytotoxicity and good biocompatibility. More importantly, active targeting via solid tumor albumin‐binding protein receptor and enhanced permeability and retention effect, the probe can be specifically aggregated to the tumor site of the 8305C tumor model and exhibit excellent MR/NIRF imaging properties. Our results show that MnO2@BSA‐Cy5.5 has high resolution and sensitivity in tumor imaging and is expected to be applied as an MR/NIRF contrast agent for accurate diagnosis of thyroid cancer. [ABSTRACT FROM AUTHOR]

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The application of soft materials, including gels, in different material and biological chemistry domains has gained momentum in the past few years. Environmental remediation, drug resistance, and delivery are significant concerns that are being investigated widely nowadays. In this work, we report the multifunctionality of a gelator molecule A2 (5,5′-((6-(phenylamino)-1,3,5-triazine-2,4-diyl)-bis-(azanediyl))-diisophthalic acid) in the gel state. The gelator molecule A2 was used to fabricate organogel and two metallogels using copper perchlorate and a Ru-based anticancer drug molecule, respectively. The organogel and Cu-metallogel show efficient adsorption capabilities of iodine in the vapor and solution phases. These iodine-loaded gel composites were utilized as efficient antibacterial agents against Escherichia coli and Helicobacter pylori (I10) bacterial strains. Additionally, owing to the pH-responsive nature of the gel material, the Ru-based anticancer drug-loaded metallogel, Ru-A2, was fabricated, and its activity in pH-responsive drug delivery to the cancerous cells was also investigated. [ABSTRACT FROM AUTHOR]

Comprehensive Summary Regulating brain iron metabolism and reducing neuronal ferroptosis is proven to be a potential method for treating Alzheimer's disease (AD). However, gastric juice has a pH of 1.1—2.2 where a large number of interfering ions are dissociated from the food, which in turn causes traditional oral iron chelators to be saturated and inactivated. Herein, poly(4‐vinylbenzoic acid) polymer chains were introduced as guided by Fe3+ ion template into the porous network (TpPa‐1) via molecularly imprinted technology to obtain porous iron chelators, COOH@TpPa‐1. The COOH@TpPa‐1 maintains a multiple hydrogen bonding structure to block the channels in the stomach (pH ~1.1—2.2) with a strongly acidic environment, so just a small amount of active sites have been occupied. As COOH@TpPa‐1 enters the colon, the alkaline environment disrupts the original hydrogen‐bonded structure and forms anionic fragments, the bonding affinity for Fe3+ ions was ~4.0 times that in the stomach, and also gave a high selective coefficient 4.2 times higher than that of conventional iron chelators. These designable "on" and "off" states promote the effective enrichment of iron ions within the colon by the porous chelator and produce a favorable therapeutic effect on Alzheimer's symptoms caused by ferroptosis in mice. [ABSTRACT FROM AUTHOR]

The development of activatable nanoplatforms to enhance diagnostic and therapeutic performance while minimizing side effects is of great significance in treatment of chronic hepatitis B (CHB). Here, we report a novel nanomaterial composed of graphitic carbon nitride (g-C3N4) and 5-aminolevulinic acid (5-ALA), onto which our newly synthesized compound 1 is loaded, forming 5-ALA/g-C3N4@1. This nanomaterial is highly pH-sensitive and can rapidly degrade in mildly acidic environments, enabling the release of its loaded photosensitizer and compound 1, exhibiting characteristics such as fluorescence recovery and increased singlet oxygen generation. We evaluated the bioactivity of this novel composite material and explored its mechanisms of action. The effect of 5-ALA/g-C3N4@1 on the levels of HBV DNA, HBsAg and HBeAg was evaluated by treatment of HepG2.2.15 cells with the system. Our results suggest that the system can effectively inhibit HBV replication for the treatment of CHB. This work presents a novel photosensitive carrier with excellent biocompatibility and therapeutic efficacy, offering new insights into CHB research. [ABSTRACT FROM AUTHOR]

In this study, poly(HEMA-PEGxMEM-IA) hydrogels were prepared by radical copolymerization of poly(ethylene glycol) methyl ether methacrylate (PEGxMEM), 2-hydroxyethyl methacrylate (HEMA), and itaconic acid (IA). The reaction was carried out in ethanolic solution using N,N′-methylenebisacrylamide (MBA) as a crosslinking agent and 1-hydroxycyclohexyl phenyl ketone (HCPK) as a photo-initiator. The poly(HEMA-PEGxMEM-IA) hydrogels (HGx) were evaluated as a delivery system for ursolic acid (UA), a phytochemical extracted from the plant Clinopodium revolutum, "flor de arena". The hydrogels were characterized by Fourier-transform infrared spectroscopy (FTIR-ATR), Raman spectroscopy, X-Ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The swelling behavior was studied in buffer solutions from pH 2 to 10, specifically at pH 2.2 (gastric environment) and 7.4 (intestinal environment). It was found that the hydrogels studied showed sensitivity to pH. At pH 2.2, the degree of swelling for HG5 and HG9 hydrogels was 0.45 and 0.93 (g water/g hydrogel), respectively. At pH 7.4, the degree of swelling for HG5 and HG9 hydrogels was 1.97 and 2.64 (g water/g hydrogel), respectively. The SEM images show the variation in pore size as a function of pH, and the UA crystals in the pores of the hydrogels can also be observed. The in vitro UA release data best fit the Korsmeyer–Peppas kinetic model and the diffusion exponent indicates that the release mechanism is governed by Fickian diffusion. [ABSTRACT FROM AUTHOR]

The incorporation of natural products into a suitable delivery system has the potential to augment their therapeutic effectiveness significantly. In this study, we demonstrate how silicasomes, a lipid‐coated mesoporous silica nanorods, influence the anticancer potency and release behaviour of the natural product. Piperlongumine (Pip), a natural product isolated from long pepper, is loaded into mesoporous silica nanorods (MSNRs) followed by a bilayer coating made of 1,2‐Dimyristoyl‐sn‐glycero‐3‐phosphocholine (DMPC). The size and morphology of Pip‐loaded MSNRs (Pip@MSNRs) and phospholipid‐coated Pip@MSNRs (PL‐Pip@MSNRs) are characterized well using suitable analytical techniques. The release of Pip from Pip@MSNRs attained saturation at 48 h while PL‐Pip@MSNRs exhibited the same only after 100 h in both simulated physiological and endolysosomal acidic environments. Moreover, PL‐Pip@MSNRs displayed a higher percentage of Pip release in an acidic medium than in a physiological medium after 24 h. These results confirm that the DMPC coating could assist the pH‐responsive and sustained release of loaded drug from silica nanorods. Most importantly, PL‐Pip@MSNRs demonstrate a higher potency of cytotoxicity and apoptosis against MCF‐7 (Human Breast Carcinoma) cells than the Pip@MSNRs, emphasizing the significance of DMPC‐coated MSNRs as a suitable nanocarrier for natural product delivery. [ABSTRACT FROM AUTHOR]

With the rapid development of the maritime industry, oily wastewater discharges and oil spills cause acute environmental challenges. Currently, cellulosic materials with switchable wettability have received increasing interest for oil–water separation. Moreover, work efficiency needs to be improved with a shorter response time. To realize these, dimethylaminoethyl methacrylate (DMAEMA) and methyltrimethoxysilane (MTMS) synthesized pH‐responsive copolymer (DMAEMA‐co‐MTMS) which grafted banana nanocellulose fiber made from wasted pseudostem to achieve the pH‐responsive aerogel (BCNA‐DcoM). BCNA‐DcoM exhibited hydrophilic/submerged lipophobicity under acidic conditions and hydrophobic/lipophilic under alkaline conditions. A response time of 3 s and a contact angle of 135° were shown when the mass ratio of banana nanocellulose suspension, MTMS, and DMAEMA‐co‐MTMS was 5:3:9. Moreover, BCNA‐DcoM possessed favorable mechanical friction properties, salt resistance (25% NaCl), compression resilience (50 cycles of compression at 60% strain), switchable wettability (>30 cycles), and highly efficient separation performance (>96%). The adsorption capacity of BCNA‐DcoM for oil is 80–184 times the initial weight of the aerogel based on the different oil densities. For practical applications, BCNA‐DcoM could continuously separate oil–water mixtures with the constant‐flow pump. The present work provides more possibilities for rapidly treating industrial oily wastewater with low‐cost and ecological banana pseudostem materials. [ABSTRACT FROM AUTHOR]

With breast cancer emerging as a pressing global health challenge, characterized by escalating incidence rates and geographical disparities, there is a critical need for innovative therapeutic strategies. This comprehensive research navigates the landscape of nanomedicine, specifically focusing on the potential of magnetic nanoparticles (MNPs), with magnetite (Fe3O4) taking center stage. MNPs, encapsulated in biocompatible polymers like silica known as magnetic silica nanoparticles (MSN), are augmented with phosphotungstate (PTA) for enhanced chemodynamic therapy (CDT). PTA is recognized for its dual role as a natural chelator and electron shuttle, expediting electron transfer from ferric (Fe3+) to ferrous (Fe2+) ions within nanoparticles. Additionally, protein-based charge-reversal nanocarriers like silk sericin and gluten are introduced to encapsulate (MSN-PTA) nanoparticles, offering a dynamic facet to drug delivery systems for potential revolutionization of breast cancer therapy. This study successfully formulates and characterizes protein-coated nanocapsules, specifically MSN-PTA-SER, and MSN-PTA-GLU, with optimal physicochemical attributes for drug delivery applications. The careful optimization of sericin and gluten concentrations results in finely tuned nanoparticles, showcasing uniform size, enhanced negative zeta potential, and remarkable stability. Various analyses, from Dynamic Light Scattering (DLS) and scanning electron microscopy (SEM) to transmission electron microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), X-Ray diffraction analysis (XRD), and Thermogravimetric analysis (TGA), provide insights into structural integrity and surface modifications. Vibrating Sample Magnetometer (VSM) analysis underscores superparamagnetic behavior, positioning these nanocapsules as promising candidates for targeted drug delivery. In vitro evaluations demonstrate dose-dependent inhibition of cell viability in MCF-7 and Zr-75–1 breast cancer cells, emphasizing the therapeutic potential of MSN-PTA-SER and MSN-PTA-GLU. The interplay of surface charge and pH-dependent cellular uptake highlights the robust stability and versatility of these nanocarriers in tumor microenvironment, paving the way for advancements in targeted drug delivery and personalized nanomedicine. This comparative analysis explores the suitability of silk sericin and gluten, unraveling a promising avenue for the development of advanced, targeted, and efficient breast cancer treatments. [ABSTRACT FROM AUTHOR]

Carbon nanodots (CDs) possess exceptional fluorescence properties, which have been extensively studied in the fields of fluorescence detection and anti‐counterfeiting information. However, the exploration of CDs with simple and fast synthesis paths, secure, and efficient encryption properties, remains a challenge. The rapid synthesis of orange CDs (O‐CDs) is reported with a high photoluminescence quantum yield (PLQY) of 57.6% within 10 min at atmospheric pressure using a one‐step pyrolysis method. The O‐CDs exhibit a dual‐emission property, with a blue emission peak at 425 nm and a strong orange emission peak at 590 nm. The dual‐emission peaks of O‐CDs can allow for fast orange/blue switching of fluorescence color with changes in the acid‐base environment. O‐CDs can serve as effective fluorescent probes for pH detection, depending on their fluorescence wavelength and intensity. Additionally, O‐CDs have potential for fluorescence anti‐counterfeiting. When exposed to NH3 gas, O‐CDs fluorescent ink rapidly (1 s) transitions from orange fluorescence to blue fluorescence, and then quickly (4 s) reverts back to orange fluorescence when the gas environment changes to HCl gas atmosphere. Thus, O‐CDs fluorescent inks offer several advantages, including high fluorescence intensity, fast response, recyclability, and lossless encryption/decryption in "on‐off‐on" double encryption anti‐counterfeiting. [ABSTRACT FROM AUTHOR]

A dual zwitterionic diblock copolymer (M100C100) consisting of poly(2‐(methacryloyloxy)ethyl phosphorylcholine) (PMPC, M) and poly(3‐((2‐(methacryloyloxy)ethyl) dimethylammonio) propionate) (PCBMA, C) is synthesized via reversible addition‐fragmentation chain transfer (RAFT) polymerization. A double hydrophilic diblock copolymer (M100S100) consist of PMPC and anionic poly(3‐sulfopropyl methacrylate potassium salt) (PMPS, S) is synthesized via RAFT. The degrees of polymerization of each block are 100. The charges of PMPC are neutralized intramolecularly. At neutral pH, the charges in PCBMA are also neutralized intramolecularly due to its carboxybetaine structure. Under acidic conditions, PCBMA exhibits polycation behavior as the pendant carboxy groups become protonated, forming cationic tertiary amine groups. PMPS shows permanent anionic nature independent of pH. Charge neutralized mixture of cationic M100C100 and anionic M100S100 in acidic aqueous solution forms water‐soluble polyion complex (PIC) micelle owing to electrostatic attractive interactions. The core is composed of the cationic PCBMA and anionic PMPS blocks, with the PMPC blocks serving as shells that covered the core surface, forming spherical core–shell PIC micelles. Above pH 4 the pendant carboxy groups in PCBMA undergo deprotonation, transitioning to a zwitterionic state, thereby eliminating the cationic charge in PCBMA. Therefore, above pH 4 the PIC micelles are dissociated due to the disappearance of the charge interactions. [ABSTRACT FROM AUTHOR]

XingYun Liu,1,* JingDuo Zhao,2,* FuRong Liu,1 ZhiZhong Xie,2 XiaoYong Lei,2 Zhe Wang,3 Zerui Yang,4 YuSheng Zhou,1,3 GuoTao Tang2 1The Affiliated Nanhua Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China; 2Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, People’s Republic of China; 3The Second Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China; 4NMPA Key Laboratory for Technology Research and Evaluation of Pharmacovigilance, Guangdong Pharmaceutical University, Guangzhou, 510086, People’s Republic of China*These authors contributed equally to this workCorrespondence: YuSheng Zhou, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China, Email yszhou08@126.com GuoTao Tang, Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang Medical School, Hengyang, Hunan, 421001, People’s Republic of China, Email tgtzq@163.comBackground: Breast cancer treatment has been a global puzzle, and targeted strategies based on the hypoxic tumor microenvironment (TME) have attracted extensive attention. As a signature transcription factor overexpressed in hypoxia tumor, hypoxia-inducible factor-1 (HIF-1) contribute to cancer progression. Compound 7-(3-(2-chloro-1H-benzo[d]1midazole-1-yl) propoxy)-2-(3,4,5-trime-thoxyphenyl)-4H-chromen-4-one, synthesized and named FB15 in our earlier research, a potential inhibitor of HIF-1α signaling pathway, has been proved a promising drug candidate for many kinds of cancer chemotherapy. However, the poor solubility and undesirable pharmacokinetics of FB15 leads to limited treatment efficacy of tumor, which ultimately restricts its potential clinical applications. Carbonic anhydrase IX (CAIX), a tumor cell transmembrane protein, was overexpressed in hypoxia tumor site. Acetazolamide (AZA), a highly selective ligand targeting CAIX, can be utilized to delivery FB15 to hypoxia tumor site.Methods: In this study, we prepared and characterized FB15 loaded nano-mixed micelles with the AZA conjugated poloxamer 188 (AZA-P188) and D-a-Tocopherol Polyethylene 1000 Glycol Succinate (TPGS), denoted as, AZA-P188/TPGS@FB15. Its delivery efficiency in vitro and in vivo was assessed by in vitro drug release, cytotoxicity assay, cellular uptake, and in vivo pharmacokinetics and fluorescence imaging. Finally, therapeutic effect of AZA-P188/TPGS@FB15 was investigated using a preclinical breast cancer subcutaneous graft model in vivo.Results: In vitro studies revealed that AZA-P188/TPGS@FB15 could efficiently target breast cancer cells mediated by CAIX receptor, trigger FB15 release in response to acidic condition, and enhance cellular uptake and cytotoxicity against breast cancer cells. The pharmacokinetic studies showed that FB15-loaded AZA-functionalized micelles exhibited significantly increased AUC0-t over free FB15. In vivo imaging demonstrated that AZA-functionalized micelles significantly increased the drug distribution in the tumor site. In vivo experiments confirmed that AZA-P188/TPGS@FB15 exhibited superior inhibition of tumor growth in nude mice with good biosafety.Conclusion: AZA-P188/TPGS@FB15 hold promise as a potentially effective therapeutic way for breast cancer. Its targeted delivery system utilizing AZA as a carrier shows potential for improving the efficacy of FB15 in cancer therapy.Keywords: carbonic anhydrase IX-targeting, FB15, hypoxia inducible factor-1, nano-mixed micelles, pH-responsive

Ling Wang,1– 3,* Fangqing Cai,3,* Yixuan Li,3,* Xiaolan Lin,3 Yuting Wang,3 Weijie Liang,3 Caiyu Liu,4 Cunze Wang,3 Junshan Ruan1– 3 1School of Pharmacy, Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 2Molecular Biology Laboratory of Traditional Chinese Medicine, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 3School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 4School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junshan Ruan, School of Pharmacy, Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, 134 Dongjie, Fuzhou, 350001, People’s Republic of China, Tel +86 591-88216343, Fax +86 591-87532356, Email ruanjunshan@163.comPurpose: Renal cell carcinoma (RCC) is the most common and lethal type of urogenital cancer, with one-third of new cases presenting as metastatic RCC (mRCC), which, being the seventh most common cancer in men and the ninth in women, poses a significant challenge. For patients with poor prognosis, temsirolimus (TEM) has been approved for first-line therapy, possessing pharmacodynamic activities that block cancer cell growth and inhibit proliferation-associated proteins. However, TEM suffers from poor water solubility, low bioavailability, and systemic side effects. This study aims to develop a novel drug formulation for the treatment of RCC.Methods: In this study, amphiphilic block copolymer (poly(ethylene glycol) monomethyl ether-poly(beta-amino ester)) (mPEG-PBAE) was utilized as a drug delivery vehicle and TEM-loaded micelles were prepared by thin-film hydration method by loading TEM inside the nanoparticles. Then, the molecular weight of mPEG-PBAE was controlled to make it realize hydrophobic–hydrophilic transition in the corresponding pH range thereby constructing pH-responsive TEM-loaded micelles. Characterization of pH-responsive TEM-loaded nanomicelles particle size, potential and micromorphology while its determination of drug-loading properties, in vitro release properties. Finally, pharmacodynamics and hepatorenal toxicity were further evaluated.Results: TEM loading in mPEG-PBAE increased the solubility of TEM in water from 2.6 μg/mL to more than 5 mg/mL. The pH-responsive TEM-loaded nanomicelles were in the form of spheres or spheroidal shapes with an average particle size of 43.83 nm and a Zeta potential of 1.79 mV. The entrapment efficiency (EE) of pH-responsive TEM nanomicelles with 12.5% drug loading reached 95.27%. Under the environment of pH 6.7, the TEM was released rapidly within 12 h, and the release rate could reach 73.12% with significant pH-dependent characteristics. In vitro experiments showed that mPEG-PBAE preparation of TEM-loaded micelles had non-hemolytic properties and had significant inhibitory effects on cancer cells. In vivo experiments demonstrated that pH-responsive TEM-loaded micelles had excellent antitumor effects with significantly reduced liver and kidney toxicity.Conclusion: In conclusion, we successfully prepared pH-responsive TEM-loaded micelles. The results showed that pH-responsive TEM-loaded micelles can achieve passive tumor targeting of TEM, and take advantage of the acidic conditions in tumor tissues to achieve rapid drug release.Keywords: renal cell carcinoma, drug delivery, pH-responsive, mPEG-PBAE, nanomicelles

[Display omitted] Premature drug release in chemotherapy and hypoxic conditions in photodynamic therapy (PDT) are perplexing problems in tumor treatment. Thus, it is of great significance to develop the novel therapeutic system with controllable drug release and effective oxygen generation. Herein, a pH-responsive oxygen self-sufficient smart nanoplatform (named DHCCC), integrating hollow mesoporous silica nanoparticles (HMSNs), chitosan (CS), doxorubicin hydrochloride (DOX), chlorin e6 (Ce6) and catalase (CAT), is fabricated to enhance the tumor therapeutic efficacy efficiently through avoiding premature drug release and mitigating hypoxia of tumor microenvironment (TME). The drug DOX can be efficiently loaded into the HMSNs with large cavity and be controllable released because of the pH responsiveness of CS to the weak acidic TME, thereby elevating the chemotherapy efficacy. Meanwhile, CAT can catalyze the decomposition of endogenous hydrogen peroxide in situ generating oxygen to alleviate the hypoxia and enhance the PDT efficiency considerably. In vitro and in vivo results demonstrate that the combined chemo-photodynamic therapy based on the DHCCC nanoplatform exerts more effective antitumor efficacy than chemotherapy or PDT alone. The current study provides a promising inspiration to construct the pH-responsive oxygen self-sufficient smart nanomedicine with potentials to prevent premature drug leakage and overcome hypoxia for efficient tumor therapy. [ABSTRACT FROM AUTHOR]

In this study, a metal-organic framework (MOF)-based prodrug was synthesized through a Schiff base reaction between UiO-66-NH2 and 3,4-dihydroxybenzaldehyde (DHBD) drug, resulting in the formation of DHBD@MOF prodrug containing a pH-sensitive C = N bond. Additionally, a dual pH-responsive drug delivery platform was developed, which encapsulated both 5-Fluorouracil (5-FU) drug and DHBD@MOF prodrug within a hydrogel composed of carboxymethyl cellulose (CMC) and alginate (Alg.). The characteristics were analyzed using PXRD, FT-IR, FE-SEM, TEM, and BET. The release studies demonstrated that the hydrogel effectively protected the platform from burst release in the acidic conditions of the stomach and small intestine. Only 1.31% release of DHBD from DHBD@MOF/5-FU@hydrogel was observed after 2.5 h at pH 1.2, compared to near 90% release from DHBD@MOF prodrug under the same conditions. Upon swelling of the hydrogel in the intestine and colorectum at pH around 6.5–7.4, pH-sensitive C = N bonding of DHBD@MOF was cleaved at acidic colorectal cancer sites, activating the inactive prodrug. Furthermore, the hydrogel facilitated controlled release of DHBD and 5-FU in simulated gastric fluid (SGF) at different pH levels (1.2, 4.5, 7.4, and 6.5). The gradual release of DHBD from hydrogel in the intestine (pH 7.4, 8.5 h) and colorectum (pH 6.5, 24 h) was 10.60% and 41.68%, respectively. This allowed for significant accumulation of the inactive DHBD@MOF prodrug at acidic tumor sites, with 89.40% and 58.32% accessing the tumors after 8.5 h and 24 h, respectively. The findings of this research hold promise for applications in medical science and pharmaceutics after in vivo experiments. [ABSTRACT FROM AUTHOR]

Combining photodynamic therapy (PDT) with chemodynamic therapy (CDT) has been proven to be a promising strategy to improve the treatment efficiency of cancer, because of the synergistic therapeutic effect arising between the two modalities. Herein, we report an inorganic nanoagent based on ternary NiCoTi-layered double hydroxide (NiCoTi-LDH) nanosheets to realize highly efficient photodynamic/chemodynamic synergistic therapy. The NiCoTi-LDH nanosheets exhibit oxygen vacancy-promoted electron-hole separation and photogenerated hole-induced O2-independent reactive oxygen species (ROS) generation under acidic circumstances, realizing in situ pH-responsive PDT. Moreover, due to the effective conversion between Co3+ and Co2+ caused by photogenerated electrons, the NiCoTi-LDH nanosheets catalyze the release of hydroxyl radicals (·OH) from H2O2 through Fenton reactions, resulting in CDT. Laser irradiation enhances the catalyzed ability of the NiCoTi-LDH nanosheets to promote the ROS generation, resulting in a better performance than TiO2 nanoparticles at pH 6.5. In vitro and in vivo experimental results show conclusively that NiCoTi-LDH nanosheets plus irradiation lead to efficient cell apoptosis and significant inhibition of tumor growth. This study reports a new pH-responsive inorganic nanoagent with oxygen vacancy-promoted photodynamic/chemodynamic synergistic performance, offering a potentially appealing clinical strategy for selective tumor elimination.

Boye Zhang,1,2 Jianliang Man,3,4 Lingyun Guo,1 Xiaoxia Ru,1 Chengwu Zhang,1,2 Wen Liu,1,2,5 Lihong Li,1,2,5 Sufang Ma,1,2 Lixia Guo,2,4 Haojiang Wang,1,2 Bin Wang,1,2 Haipeng Diao,1,5 Renchao Che,6,7 Lili Yan1,2,5 1School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 2Shanxi Province Brain Degenerative Diseases Precision Diagnosis and Treatment Engineering Research Center, Shanxi Medical University, Jinzhong, 030606, People’s Republic of China; 3Academy of Medical Sciences, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 4College of Pharmacy, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 5Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 6Laboratory of Advanced Materials, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Academy for Engineering &Technology, Fudan University, Shanghai, 200438, People’s Republic of China; 7Zhejiang Laboratory, Hangzhou, 311100, People’s Republic of ChinaCorrespondence: Lili Yan; Renchao Che, Email yanlili@sxmu.edu.cn; rcche@fudan.edu.cnBackground: Challenges such as poor drug selectivity, non-target reactivity, and the development of drug resistance continue to pose significant obstacles in the clinical application of cancer therapeutic drugs. To overcome the limitations of drug resistance in chemotherapy, a viable treatment strategy involves designing multifunctional nano-platforms that exploit the unique physicochemical properties of tumor microenvironment (TME).Methods: Herein, layer-by-layer nanoparticles with polyporous CuS as delivery vehicles, loaded with a sonosensitizer (tetra-(4-aminophenyl) porphyrin, TAPP) and sequentially functionalized with pH‐responsive CaCO3, targeting group hyaluronic acid (HA) were designed and synthesized for synergistic treatment involving chemodynamic therapy (CDT), sonodynamic therapy (SDT), photothermal therapy (PTT), and calcium overload. Upon cleavage in an acidic environment, CaCO3 nanoparticles released TAPP and Ca2+, with TAPP generating 1O2 under ultrasound trigger. Exposed CuS produced highly cytotoxic ·OH in response to H2O2 and also exhibited a strong PTT effect.Results: CuS@TAPP-CaCO3/HA (CTCH) delivered an enhanced ability to release more Ca2+ under acidic conditions with a pH value of 6.5, which in situ causes damage to HeLa mitochondria. In vitro and in vivo experiments both demonstrated that mitochondrial dysfunction greatly amplified the damage caused by reactive oxygen species (ROS) to tumor, which strongly confirms the synergistic effect between calcium overload and reactive oxygen therapy.Conclusion: Collectively, the development of CTCH presents a novel therapeutic strategy for tumor treatment by effectively responding to the acidic TME, thus holding significant clinical implications.Keywords: mitochondria damage, calcium overload, reactive oxygen oncotherapy, pH-responsive, synergistic treatment

Qing Lin,1,2,* Yafei Jing,2,3,* Cailing Yan,2 Xinyi Chen,2 Qiong Zhang,2 Xinhua Lin,2,3 Yunlu Xu,2,4 Bing Chen2,3 1Department of Pharmacy, Affiliated Fuzhou First Hospital of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2School of Pharmacy, Fujian Medical University, Fujian, People’s Republic of China; 3Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Center of Translational Hematology, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bing Chen, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email BingChen_001@126.com; BingChen_001@fjmu.edu.cn Yunlu Xu, Center of Translational Hematology, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email xuyunlu3578@126.comBackground: Current immunotherapies with unexpected severe side effects and treatment resistance have not resulted in the desired outcomes for patients with melanoma, and there is a need to discover more effective medications. Cytotoxin (CTX) from Cobra Venom has been established to have favorable cytolytic activity and antitumor efficacy and is regarded as a promising novel anticancer agent. However, amphiphilic CTX with excellent anionic phosphatidylserine lipid-binding ability may also damage normal cells.Methods: We developed pH-responsive liposomes with a high CTX load (CTX@PSL) for targeted acidic-stimuli release of drugs in the tumor microenvironment. The morphology, size, zeta potential, drug-release kinetics, and preservation stability were characterized. Cell uptake, apoptosis-promoting effects, and cytotoxicity were assessed using MTT assay and flow cytometry. Finally, the tissue distribution and antitumor effects of CTX@PSL were systematically assessed using an in vivo imaging system.Results: CTX@PSL exhibited high drug entrapment efficiency, drug loading, stability, and a rapid release profile under acidic conditions. These nanoparticles, irregularly spherical in shape and small in size, can effectively accumulate at tumor sites (six times higher than free CTX) and are rapidly internalized into cancer cells (2.5-fold higher cell uptake efficiency). CTX@PSL displayed significantly stronger cytotoxicity (IC50 0.25 μg/mL) and increased apoptosis in than the other formulations (apoptosis rate 71.78± 1.70%). CTX@PSL showed considerably better tumor inhibition efficacy than free CTX or conventional liposomes (tumor inhibition rate 79.78± 5.93%).Conclusion: Our results suggest that CTX@PSL improves tumor-site accumulation and intracellular uptake for sustained and targeted CTX release. By combining the advantages of CTX and stimuli-responsive nanotechnology, the novel CTX@PSL nanoformulation is a promising therapeutic candidate for cancer treatment.Keywords: cobra venom cytotoxin, tumor microenvironment, pH-responsive, targeted delivery, liposomes

Yun Liu,1,2 Timo Hamm,3 Thomas Ralf Eichinger,3 Walter Kamm,3 Heike Andrea Wieland,3 Brigitta Loretz,1 Anna KH Hirsch,2,4 Sangeun Lee,1,2 Claus-Michael Lehr1,2 1Department of Drug Delivery Across Biological Barriers, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, Germany; 2Department of Pharmacy, Saarland University, Saarbrücken, Germany; 3Department of Research and Development, Sanofi-Aventis Deutschland GmbH, Frankfurt Am Main, Germany; 4Department of Drug Design and Optimisation, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, GermanyCorrespondence: Claus-Michael Lehr, Department of Drug Delivery Across Biological Barriers, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, Germany, Tel +49 681 98806-1000, Fax +49 681 98806 1009, Email Claus-Michael.Lehr@helmholtz-hips.de Sangeun Lee, Department of Pharmacy, Saarland University, Saarbrücken, Germany, Tel +49 681 302 4764, Fax +49 681 302 2028, Email Sangeun.Lee@uni-saarland.deBackground: Therapeutic proteins and peptides offer great advantages compared to traditional synthetic molecular drugs. However, stable protein loading and precise control of protein release pose significant challenges due to the extensive range of physicochemical properties inherent to proteins. The development of a comprehensive protein delivery strategy becomes imperative accounting for the diverse nature of therapeutic proteins.Methods: Biodynamers are amphiphilic proteoid dynamic polymers consisting of amino acid derivatives connected through pH-responsive dynamic covalent chemistry. Taking advantage of the amphiphilic nature of the biodynamers, PNCs and DEs were possible to be prepared and investigated to compare the delivery efficiency in drug loading, stability, and cell uptake.Results: As a result, the optimized PNCs showed 3-fold encapsulation (< 90%) and 5-fold loading capacity (30%) compared to DE-NPs. PNCs enhanced the delivery efficiency into the cells but aggregated easily on the cell membrane due to the limited stability. Although DE-NPs were limited in loading capacity compared to PNCs, they exhibit superior adaptability in stability and capacity for delivering a wider range of proteins compared to PNCs.Conclusion: Our study highlights the potential of formulating both PNCs and DE-NPs using the same biodynamers, providing a comparative view on protein delivery efficacy using formulation methods. Keywords: amphiphilic polymer, nanocomplex, double emulsion, pH-responsive, protein delivery, dynamic covalent chemistry

The nanoparticle-induced endothelial leakiness effect can enhance the ability of nanoparticles (NPs) to cross the vascular barrier but also promote pathological processes. The rarity of NPs capable of endothelial penetration without adverse effects underscores a critical challenge. Addressing this, we designed a bivalve pH-responsive pathway that controlled self-shedding NPs. At its core lies a composite structure comprising indocyanine green-doped spiky SiO2 NPs within an inner-shell comprising the cationic polymer polyethylenimine (PEI), tethered to the core via hydrazone linkages, alongside the inclusion of the endothelial recovery factor angiopoietin-1 (Ang1) and an outermost biomimetic cell membrane shell. In drug delivery, our NPs can target and traverse the endothelial barrier. Then, the initiation of the first self-shedding process ensues upon exposure to an acidic milieu, eliciting the proton sponge effect facilitated by PEI, thereby inducing membrane rupture and enabling NP release, while at the same time, Ang1 is released to repair the disrupted endothelial barrier. Furthermore, the hydrazone bonds were broken in the more acidic environment closer to the tumor site to realize the second self-shedding process, which reproduced the spiky morphology for promoted endocytosis. Therefore, the designed self-shedding NPs can realize two steps of self-shedding to inhibit tumor metastasis and improve photothermal therapy. [ABSTRACT FROM AUTHOR]

Recent advances in the field of drug delivery have opened new avenues for the development of novel nanodrug delivery systems (NDDS) in cancer therapy. Self-assembled nanoparticles (SANPs) based on tumour microenvironment have great advantages in improving antitumor effect, and pH-responsive SANPs prepared by the combination of pH-responsive nanomaterials and self-assembly technology can effectively improve the efficacy and reduce the systemic toxicity of antitumor drugs. In this review, we describe the characteristics of self-assembly and its driving force, the mechanism of pH-responsive NDDS, and the nanomaterials for pH-responsive SANPs type. A series of pH-responsive SANPs for tumour-targeted drug delivery are discussed, with an emphasis on the relation between structural features and theranostic performance. [ABSTRACT FROM AUTHOR]

In this work, we developed multifunctional hydrogel nanoparticles (NPs) that can encapsulate anticancer drugs and imaging contrast agents as well. Mitomycin C (MMC) and rhodamine B (RB) were selected as models for anticancer drugs and imaging contrasting agents, respectively. Both MMC and RB were linked to the succinated polyvinyl alcohol polymer (PVA-SA). The selected labeled hydrogel NPs ((0.5% RB)-PVA-SA NPs and (1.5% RB)-PVA-SA NPs) improved the RB quantum yield from 29.8% to a minimum of 42.7%. Moreover, they showed higher emission stability compared to free RB when they were repeatedly excited at 554 nm for 2 h. Furthermore, the dye polymeric interactions significantly increased the RB fluorescence lifetime by approximately twofold. All these optical properties pave the way for our labeled hydrogel NPs to be used in imaging-guided therapy. For the labeled MMC-loaded NPs, the MMC-binding efficiency was found to be exceedingly high in all synthesized samples: a minimum of 92% was achieved. In addition, the obtained pH-dependent drug release profiles as well as the cytotoxicity evaluation demonstrated the high potential of releasing MMC under acidic cancerous conditions. Moreover, the in vitro cellular uptake experiment confirmed the accumulation of MMC NPs throughout the cytoplasm. [ABSTRACT FROM AUTHOR]

Microencapsulated enzymes have been found to effectively accelerate cheese ripening. However, microencapsulated enzyme release is difficult to control, often resulting in enzyme release during cheese processing and causing texture and flavor defects. This study aims to address this issue by developing aminopeptidase-loaded pH-responsive chitosan microspheres (A-CM) for precise enzyme release during cheese ripening. An aminopeptidase with an isoelectric point (pH 5.4) close to the pH value of cheese ripening was loaded on chitosan microspheres through electrostatic interaction. Turbidity titration measurements revealed that pH 6.5 was optimal for binding aminopeptidase and microspheres, affording the highest loading efficiency of 58.16%. Various characterization techniques, including scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy confirmed the successful loading of aminopeptidase molecules on the chitosan microspheres. In vitro release experiments conducted during simulated cheese production demonstrated that aminopeptidase release from A-CM was pH responsive. The microspheres retained the enzyme during the coagulation and cheddaring processes (pH 5.5–6.5) and only released it after entering the cheese-ripening stage (pH 5.0–5.5). By loading aminopeptidase on chitosan microspheres, the loss rate of the enzyme in cheese whey was reduced by approximately 79%. Furthermore, compared with cheese without aminopeptidase and cheese with aminopeptidase added directly, the cheeses made with A-CM exhibited the highest proteolysis level and received superior sensory ratings for taste and smell. The content of key aroma substances, such as 2/3-methylbutanal and ethyl butyrate, in cheese with A-CM was more than 15 times higher than the others. This study provides an approach for accelerating cheese ripening through the use of microencapsulated enzymes. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, a pH-responsive polycaprolactone (PCL)–copper peroxide (CuO2) composite antibacterial coating was developed by suspension flame spraying. The successful synthesis of CuO2 nanoparticles and fabrication of the PCL-CuO2 composite coatings were confirmed by microstructural and chemical analysis. The composite coatings were structurally homogeneous, with the chemical properties of PCL well maintained. The acidic environment was found to effectively accelerate the dissociation of CuO2, allowing the simultaneous release of Cu2+ and H2O2. Antimicrobial tests clearly revealed the enhanced antibacterial properties of the PCL-CuO2 composite coating against both Escherichia coli and Staphylococcus aureus under acidic conditions, with a bactericidal effect of over 99.99%. This study presents a promising approach for constructing pH-responsive antimicrobial coatings for biomedical applications. [ABSTRACT FROM AUTHOR]

Negative immunoregulatory signal (PD-L1, CXCR4, et al.) and weak immunogenicity elicited immune system failing to detect and destroy cancerous cells. CXCR4 blockade promoted T cell tumor infiltration and increased tumor sensitivity to anti-PD-L1 therapy. Here, pH-responsive reassembled nanomaterials were constructed with anti-PD-L1 peptide and CXCR4 antagonists grafting (APAB), synergized with photothermal therapy for melanoma and breast tumor interference. The self-assembled APAB nanoparticles accumulated in the tumor and rapidly transformed into nanofibers in response to the acidic tumor microenvironment, leading to the exposure of grafted therapeutic agents. APAB enabling to reassemble around tumor cells and remained stable for over 96 h due to the aggregation induced retention (AIR) effect, led to long-term efficiently combined PD-L1 and CXCR4 blockade. Photothermal efficiency (ICG) induced immunogenic cell death (ICD) of tumor cells so as to effectively improve the immunogenicity. The combined therapy (ICG@APAB) could effectively inhibit the growth of primary tumor (∼83.52%) and distant tumor (∼76.24%) in melanoma-bearing mice, and significantly (p < 0.05) prolong the survival time over 42 days. The inhibition assay on tumor metastasis in 4 T1 model mice exhibited ICG@APAB almostly suppressed the occurrence of lung metastases and the expression levels of CD31, MMP-9 and VEGF in tumor decreased by 82.26%, 90.45% and 41.54%, respectively. The in vivo reassembly strategy will offer novel perspectives benefical future immunotherapies and push development of combined therapeutics into clinical settings. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Journal of Food Science & Biotechnology is the property of Journal of Food Science & Biotechnology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Natural gum-based flocculants are prevalent for water treatment, still their efficiency can be improved by the incorporation of eco-friendly inorganic fillers. Such inorganic–organic-based hybrid materials need to be explored more in natural and synthetic water systems for their proof of concept and related applications. Hybrid almond gum (Amg) grafted polyacrylamide/silica-based composite (Amg-g-PAM/SiO2) was synthesized and assessed as a flocculant for natural and synthetic water systems. The synthesis was characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Field emission scanning electron microscopy (FE-SEM), Energy dispersive X-ray spectroscopy (EDS), Thermogravimetric analysis (TGA), Differential scanning calorimetry (DSC) and X-ray photoelectron spectroscopy (XPS) to study the chemical, structural, thermal, and surface properties. The synthesized grades of Amg-g-PAM and Amg-g-PAM/SiO2 were tested for their flocculation performance in kaolin, iron ore and MWCNT suspensions. pH and temperature variations, zeta potential measurements were studied on neutral kaolin suspension. The best flocculation efficiency was observed to be 98%, 96%, 95% and 92% in MWCNT, kaolin, iron ore suspensions and river water respectively at pH 4 and 25 °C. Overall, Amg-g-PAM/SiO2 flocculant possesses unique characteristics of conventional branched graft copolymers which increases easy approachability towards suspended particles while its inorganic counterpart enhances adsorption. Thus, this hybrid flocculant is better than any of its individual inorganic or organic counterparts in terms of flocculation efficacy. [ABSTRACT FROM AUTHOR]

The poor targeting and high toxicity of chemotherapeutic drugs make them less effective against breast cancer. In this study, in accordance with their photothermal effect, the aptamer (Apt) (AS1411) and doxorubicin (DOX) were linked to zeolite imidazole salt frame8 (ZIF-8) by using gold nanorods (Au NRs). Thereby, a multifunctional targeting nanoparticle platform (DOX/Au-Apt@ZIF-8) was constructed to deliver and effectively utilize DOX and realize the antitumor effects of the multimodal combination of chemotherapy–target–photothermal therapy. This platform was responsive to both pH and near-infrared (NIR) light. In the characterization experiments, DOX/Au-Apt@ZIF-8 exhibited good dispersibility, particle size stability, and consistent spectral characteristics. The photothermal conversion efficiency was up to 53.5%. In the cell uptake and cell cycle experiments, DOX/Au-Apt@ZIF-8 effectively targeted tumor cells and blocked their growth in the S phase. Moreover, in an in vivo study, DOX/Au-Apt@ZIF-8 exerted good inhibitory effects and photothermal effects on tumors. When combined with NIR irradiation, DOX/Au-Apt@ZIF-8 inhibited tumor tissue growth by enhancing and inducing apoptosis. Importantly, histopathological analysis revealed that the nanoparticles were less toxic to other organs and had high biosafety. As such, DOX/Au-Apt@ZIF-8 fabricated in this study is expected to offer a treatment approach against breast cancer. [ABSTRACT FROM AUTHOR]

Nitrogen is currently the most crucial nutrient for crop growth, and the overdose of conventional urea nitrogen fertilizer has resulted in both the waste of fertilizer resource and the eutrophication of water bodies due to low nitrogen use efficiency. Herein, a smart core–shell nanocarrier (MIL-100-(Fe)/silica) was fabricated to deliver urea to enhance the use efficiency for sustainable nitrogen management. The results showed that the developed urea/MIL-100-(Fe)/silica had a stable core–shell nanostructure with a highly crystallized regular octahedron, which achieved a high nitrogen loading of 25.5%; the duration of the nitrogen release period was up to 56 days in an aqueous solution, which matched well with rice growth. The slow release of urea from the urea/MIL-100-(Fe)@silica nanocarrier was ascribed to the silica shell material and hydrogen bonding preventing the premature escape of urea from the MIL-100-(Fe) core in the environment. In a pot experiment, the nitrogen use efficiency (NUE) of urea/MIL-100-(Fe)/silica treatment (45.5%) was significantly enhanced compared to that of the urea treatment (34.7%) and promoted the grain yield by 13.07%. Therefore, the proposed fertilization strategy based on urea/MIL-100-(Fe) significantly benefited both the rice growth and nitrogen use efficiency, providing a promising nanoplatform for precise and efficient nutrient supply. [ABSTRACT FROM AUTHOR]

Design and fabrication of pH‐responsive nanofibrous membranes by biomaterials is a key step for drug delivery systems. Currently, there is an increasing attention on design of biocompatible nanofibrous drug delivery systems. Here, a bio‐based pH‐responsive nanofibrous membranes loaded with antibiotic were fabricated for the controlled release of tetracycline hydrochloride (TH). The in vitro drug release behavior of varied pH‐responsive nanofibrous with different mass ratios of poly (lactic acid) (PLA) and cellulose acetate phthalate (CAP) was investigated to clarify the release mechanism. TH initial burst release within 20 mins was large than 97.5% for PLA/CAP/TH NFM under alkaline conditions (pH = 8). The antioxidant activity of TH loaded PLA/CAP NFMs are all higher than 55% after 30 mins. The prepared fibrous membranes possess sufficient antibacterial activity against both to Gram‐negative and Gram‐positive bacteria. At the same time, it also has good biocompatibility. Therefore, the fabricated nanofibrous membranes was demonstrated to be a pH‐responsive nanoplatform for drug delivery. [ABSTRACT FROM AUTHOR]

Oxidative stress induced by excess reactive oxygen species (ROS) is a primary pathogenic cause of acute kidney injury (AKI). Development of an effective antioxidation system to mitigate oxidative stress for alleviating AKI remains to be investigated. This study presents the synthesis of an ultra‐small Platinum (Pt) sulfur cluster (Pt5.65S), which functions as a pH‐activatable prefabricated nanozyme (pre‐nanozyme). This pre‐nanozyme releases hydrogen sulfide (H2S) and transforms into a nanozyme (Ptzyme) that mimics various antioxidant enzymes, including superoxide dismutase and catalase, within the inflammatory microenvironment. Notably, the Pt5.65S pre‐nanozyme exhibits an endo‐exogenous synergy‐enhanced antioxidant therapeutic mechanism. The Ptzyme reduces oxidative damage and inflammation, while the released H2S gas promotes proneurogenesis by activating Nrf2 and upregulating the expression of antioxidant molecules and enzymes. Consequently, the Pt5.65S pre‐nanozyme shows cytoprotective effects against ROS/reactive nitrogen species (RNS)‐mediated damage at remarkably low doses, significantly improving treatment efficacy in mouse models of kidney ischemia‐reperfusion injury and cisplatin‐induced AKI. Based on these findings, the H2S‐generating pre‐nanozyme may represent a promising therapeutic strategy for mitigating inflammatory diseases such as AKI and others. [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Esophageal cancer is one of the most common cancers in the world, ranking sixth in cancer-related mortality. Doxorubicin (DOX), as a classic broad-spectrum, non-specific small-molecular anti-tumor drug, has achieved widespread use, including in the treatment of esophageal cancer. However, due to its strong cardiotoxicity, poor tumor-targeting ability, and short half-life, the clinical application of DOX has been greatly limited. In this research, we designed and successfully synthesized a peptide sequence IEIIIK (IEK for short) with excellent pH responsiveness. Under physiological conditions (pH 7.4), the peptide can encapsulate DOX and self-assemble into a stable hydrogel (DOX-IEK) through hydrophobic and electrostatic interactions. After being injected into the acidic tumor microenvironment, the protonation degree of alkaline amino acid lysine increased and the negative charge of glutamate decreased, directly leading to enhanced electrostatic repulsion and subsequent hydrogel dissociation. Released DOX can accumulate in tumor tissue and achieve anti-tumor efficacy. More importantly, the hydrogel can act as a drug reservoir for sustained drug release, improving the drug targeting ability, prolonging the duration of drug administration to compensate for the short half-life of DOX, and reducing systemic toxicity. Ideal anti-tumor efficacy has been achieved in both the in vitro and in vivo experiments.

The water-soluble tribenzotriquinacene-based hexacarboxylic acid ammonium salt, TBTQ-C 6 , acts as the host component (H) forming host–guest complexes with tetraphenylethylene (TPE)-functionalized monotopic and tetratopic quaternary ammonium derivatives, G1 and G2, to yield supra-amphiphiles. These supra-amphiphiles self-assemble to form pH-responsive fluorescent vesicles, which have allowed us to capitalize on the aggregation-induced emission (AIE) effect for imaging-guided drug delivery systems. These systems exhibit efficient drug loading and pH-responsive delivery capabilities. Upon encapsulation of the anticancer drug doxorubicin (DOX), both the TPE and DOX chromophores undergo dual-fluorescence deactivation due to the energy transfer relay (ETR) effect. Under acidic conditions, the release of DOX interrupts the ETR effect, resulting in the fluorescence recovery of TPE fluorogens and DOX, allowing for real-time visual monitoring of the drug release process. Cytotoxicity experiments confirmed the low toxicity of the unloaded vectors to normal cells, while the DOX-loaded vectors were found to significantly enhance the anticancer activity of DOX against cancer cells in vitro. The AIE-featured supramolecular vesicles presented in this research hold great potential for imaging-guided drug delivery systems.

Abstract To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis.

Abstract Background There is a continuous growth of interest in the development of nano-drug delivery systems that could combine therapy and diagnosis of cancer. Results Novel multifunctional superparamagnetic iron oxide nanoparticles (SPIONs, chemically Fe3O4) conjugated with carboxymethyl sagocellulose (CMSC), and 5-fluorouracil (Fe3O4-CMSC-5FU) were synthesized. The conjugated nanoparticles have the magnetic properties of the SPIONs, which allows the nanoparticles to be localized at the target area by applying an external magnetic field. SPIONs generate heat upon exposure to laser lights, resulting in a photothermic effect. The drug-loading efficiency of 5-FU into the SPIONs-CMSC conjugated nanoparticles was 70 to 84% w/w which could release the drug at intracellular pH (5.4) of cancer cells and resist drug release at pH 7.2. In vivo studies using mice models confirmed the nanoparticles could efficiently deliver 5-FU only to the cancer cells and the anticancer effect was enhanced by laser-induced hyperthermia. Conclusions The combination of targeted delivery of 5-FU with photothermal therapy (PTT) looks promising for selective killing of cancer cells. Furthermore, SPIONs are an excellent contrasting agent for use in computerized tomography (CT) imaging for determining the tumor location and monitoring the progress of the therapy. The focus of this work was the oncological application of multifunctional Fe3O4-CMSC-5FU nanoparticle conjugates, with an emphasis on therapeutic, diagnostic and prognostic purposes.

Wound healing in movable parts, including the joints and neck, remains a critical challenge due to frequent motions and poor flexibility of dressings, which may lead to mismatching of mechanical properties and poor fitting between dressings and wounds; thus, increasing the risk of bacterial infection. This study proposes a sprayable zwitterionic antibacterial hydrogel with outstanding flexibility and desirable adhesion. This hydrogel precursor is fabricated by combining zwitterionic sulfobetaine methacrylate (SBMA) with poly(sulfobetaine methacrylate‐co‐dopamine methacrylamide)‐modified silver nanoparticles (PSBDA@AgNPs) through robust electrostatic interactions. About 150 s of exposure to UV light, the SBMA monomer polymerizes to form PSB chains entangled with PSBDA@AgNPs, transformed into a stable and adhesion PSB–PSB@Ag hydrogel at the wound site. The resulting hydrogel has adhesive strength (15–38 kPa), large tensile strain (>400%), suitable shape adaptation, and excellent mechanical resilience. Moreover, the hydrogel displays pH‐responsive behavior; the acidic microenvironment at the infected wound sites prompts the hydrogel to rapidly release AgNPs and kill bacteria. Further, the healing effect of the hydrogel is demonstrated on the rat neck skin wound, showing improved wound closing rate due to reduced inflammation and enhanced angiogenesis. Overall, the sprayable zwitterionic antibacterial hydrogel has significant potential to promote joint skin wound healing. [ABSTRACT FROM AUTHOR]

To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis. [ABSTRACT FROM AUTHOR]

In this study, a novel selenium@zeolitic imidazolate framework core/shell nanocomposite stabilised with alginate was used to improve the anti-tumour activity of curcumin. The developed alginate-stabilised curcumin-loaded selenium@zeolitic imidazolate framework (Alg@Cur@Se@ZIF-8) had a mean diameter of 159.6 nm and polydispersity index < 0.25. The release of curcumin from the nanocarrier at pH 5.4 was 2.69 folds as high as at pH 7.4. The bare nanoparticles showed haemolytic activity of about 12.16% at a concentration of 500 µg/mL while covering their surface with alginate reduced this value to 5.2%. By investigating cell viability, it was found that Alg@Cur@Se@ZIF-8 caused more cell death than pure curcumin. Additionally, in vivo studies showed that Alg@Cur@Se@ZIF-8 dramatically reduced tumour growth compared to free curcumin in 4T1 tumour-bearing mice. More importantly, the histological study confirmed that the developed drug delivery system successfully inhibited lung and liver metastasis while causing negligible toxicity in vital organs. Overall, due to the excellent inhibitory activity on cancerous cell lines and tumour-bearing animals, Alg@Cur@Se@ZIF-8 can be considered promising for breast cancer therapy. [ABSTRACT FROM AUTHOR]

A heterograft copolymer with an alginate backbone, hetero-grafted by polymer pendant chains displaying different lower critical solution temperatures (LCSTs), combined with a pH-responsive poly(2-vinyl pyridine)-b-poly(ethylene oxide) (P2VP-b-PEO) diblock copolymer forming micellar nanoparticles, was investigated in aqueous media at various pHs. Due to its thermo-responsive side chains, the copolymer forms hydrogels with a thermo-induced sol–gel transition, above a critical temperature, Tgel (thermo-thickening). However, by lowering the pH of the medium in an acidic regime, a remarkable increase in the elasticity of the formulation was observed. This effect was more pronounced in low temperatures (below Tgel), suggesting secondary physical crosslinking, which induces significant changes in the hydrogel thermo-responsiveness, transforming the sol–gel transition to soft gel–strong gel. Moreover, the onset of thermo-thickening shifted to lower temperatures followed by the broadening of the transition zone, implying intermolecular interactions between the uncharged alginate backbone with the PNIPAM side chains, likely through H-bonding. The shear-thinning behavior of the soft gel in low temperatures provides injectability, which allows potential applications for 3D printing. Furthermore, the heterograft copolymer/nanoparticles composite hydrogel, encapsulating a model hydrophobic drug in the hydrophobic cores of the nanoparticles, was evaluated as a pH-responsive drug delivery system. The presented tunable drug delivery system might be useful for biomedical potential applications. [ABSTRACT FROM AUTHOR]

The clinical treatment of inflammatory bowel disease (IBD) is challenging. We developed copper sulfate (CuS)/disulfiram (DSF)/methacrylic acid-ethyl acrylate copolymer (EL)/polyvinylpyrrolidone (PVP) nanoplatform (CuS/DSF/EL/PVP) and evaluated its efficiency for treating IBD. After oral administration, the pH-sensitive EL protected the CuS/DSF/EL/PVP against degradation by acidic gastric juices. Once the colon was reached, EL was dissolved, releasing DSF and Cu2+. Further, the main in vivo metabolite of DSF can bind to Cu2+ and form copper (II) N, N-diethyldithiocarbamate (CuET), which significantly alleviated acute colitis in mice. Notably, CuS/DSF/EL/PVP outperformed CuS/EL/PVP and DSF/EL/PVP nanoplatforms in reducing colonic pathology and improving the secretion of inflammation-related cytokines (such as IL-4 and IL-10) in the colonic mucosa. RNA-seq analysis revealed that the nanoplatform reduced colonic inflammation and promoted intestinal mucosal repair by upregulating C-type lectin receptor (CLR)-related genes and signaling pathways. Furthermore, CuS/DSF/EL/PVP showed potential for improving colitis Th1/Th17 cells through innate immunity stimulation, down-regulation of inflammatory cytokines, and upregulation of anti-inflammatory cytokines. Additionally, the intervention with CuS/DSF/EL/PVP led to increased intestinal flora diversity, decreased Escherichia–Shigella abundance, and elevated levels of short-chain fatty acid (SCFA)-producing bacteria Prevotella, Lactobacillus , and Bifidobacterium , indicating their potential to modulate the dysregulated intestinal flora and suppress inflammation. Our study introduces the CuS/DSF/EL/PVP nanoplatform as a therapeutic strategy for treating inflammatory bowel disease (IBD). This approach demonstrates significant efficacy in targeting the colon and alleviating acute colitis in mice. It uniquely modulates gut immunity and microbiota, exhibiting a notable impact on inflammation-related cytokines and promoting intestinal mucosal repair. The nanoplatform's ability to regulate gut flora diversity, combined with its cost-effective and scalable production, positions it as a potentially transformative treatment for IBD, offering new avenues for personalized medical interventions. [Display omitted] [ABSTRACT FROM AUTHOR]

A key challenge for the effective treatment of intestinal diseases, including inflammatory bowel disease (IBD), is to develop an oral drug delivery system that can resist gastric acid erosion and efficiently release drugs after rapid entry into the intestine. In the present work, we developed oral composite nanoparticles (MSZ@PRHS) consisting of a rough mesoporous silica (RHS) loaded with Mesalazine (MSZ) and a CAP polymer membrane for targeted relief of inflammation in colitis. At the pH values of the simulated stomach and small intestine, the release rate of MSZ from MSZ@PRHS was low, while at the pH values of the simulated colon, the release rate of MSZ was high. In dextran sulfate sodium salt (DSS)-induced acute colitis mouse model, compared with oral administration of the drug Mesalazine in the equivalent solution form, oral administration of PRHS loaded with drug-loaded nanoparticles can significantly alleviate the symptoms of inflammatory bowel disease, and improve the therapeutic effect. We propose that the intestinal microenvironment provides an interface for nanocomposites switch and a promising drug delivery platform for the management and treatment of many intestinal diseases, where controlled drug release and prolonged residence time are required. [ABSTRACT FROM AUTHOR]