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The continuous supply of hydrogen sulfide (H 2 S) gas at high concentrations to tumors is considered a promising and safe strategy for tumor therapy. However, the absence of a durable and cost-effective H 2 S-producing donor hampers its extensive application. Sulfate-reducing bacteria (SRB) can serve as an excellent H 2 S factory due to their ability to metabolize sulfate into H 2 S. Herein, a novel injectable chondroitin sulfate (ChS) hydrogel loaded with SRB (SRB@ChS Gel) is proposed to sustainably produce H 2 S in tumor tissues to overcome the limitations of current H 2 S gas therapy. In vitro, the ChS Gel not only supports the growth of encapsulated SRB, but also supplies a sulfate source to the SRB to produce high concentrations of H 2 S for at least 7 days, resulting in mitochondrial damage and immunogenic cell death. Once injected into tumor tissue, the SRB@ChS Gel can constantly produce H 2 S for >5 days, significantly inhibiting tumor growth. Furthermore, such treatment activates systemic anti-tumor immune responses, suppresses the growth of distant and recurrent tumors, as well as lung metastases, meanwhile with negligible side effects. Therefore, the injectable SRB@ChS Gel, as a safe and long-term, self-sustained H 2 S-generating factory, provides a promising strategy for anti-tumor therapy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The application of numerous chemotherapeutic drugs has been limited due to poor solubility, adverse side effects, and even multidrug resistance in patients. Polymeric micelles with reversibly cross-linked structures provide a promising solution to these issues. Herein, we optimized and synthesized programable-released disulfide cross-linked micelle (PDCM) based on our previous well-defined dendrimers to deliver the antitumor drug betulinic acid (BA) and paclitaxel (PDCM@PTX) and evaluated the therapeutic efficacy of multidrug-resistant (MDR) simulative orthotopic intraperitoneal ovarian cancer mice models. Comprehensive results demonstrated that PDCM@PTX formed stable nanoparticles able to improve the pharmacokinetic profile and circulation time of PTX, allowing for increased tumor penetration. Furthermore, in the tumor microenvironment, the programable-switches (ester bonds and disulfide cross-linking) of PDCM@PTX were cleaved by the high concentration of glutathione (tumor microenvironment) and esterase (intracellular) present in the tumor, allowing for in situ release of PTX and BA, resulting in intensive therapeutic efficacy in MDR ovarian cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Chitosan is a natural polymer with acceptable biocompatibility, biodegradability, and mechanical stability; hence, it has been widely appraised for drug and gene delivery applications. However, there has been no comprehensive assessment to tailor-make chitosan cross-linkers of various types and functionalities as well as complex chitosan-based semi- and full-interpenetrating networks for drug delivery systems (DDSs). Herein, various fabrication methods developed for chitosan hydrogels are deliberated, including chitosan crosslinking with and without diverse cross-linkers. Tripolyphosphate, genipin and multi-functional aldehydes, carboxylic acids, and epoxides are common cross-linkers used in developing biomedical chitosan for DDSs. Methods deployed for modifying the properties and performance of chitosan hydrogels, via their composite production (semi- and full-interpenetrating networks), are also cogitated here. In addition, recent advances in the fabrication of advanced chitosan hydrogels for drug delivery applications such as oral drug delivery, transdermal drug delivery, and cancer therapy are discussed. Lastly, thoughts on what is needed for the chitosan field to continue to grow is also debated in this comprehensive review article., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Despite a diverse range of active pharmaceutical agents currently at our disposal, high morbidity rate diseases continue to pose a major health crisis globally. One of the important parameters in this regard is the controlled cargo delivery at desired sites. Among a variety of synthetic and natural macromolecular systems, chitosan, an abundant biopolymer, offers a platform for tailored architectures that could have high loading capacity of cargo, target and deliver. Stimuli directed accumulation of vehicles and drug release is an area of direct relevance to biomedical applications. In this review, we highlight essential characteristics of modified chitosan that present themselves for efficient response through an internal (glutathione, reactive oxygen species, pH, temperature, enzymes, and chemical/electrical potential gradient), and external stimuli (ultrasound, light, mechanical stimuli, magnetic and electrical fields). With a brief review of the pertinent properties of chitosan that are relevant to biology, the design and critical evaluation of varied chitosan-based platforms is discussed. Future directions in exploiting important features of chitosan in this area can be derived from the presented comparative evaluation of the current literature in drug delivery., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Chitosan (CS) is a material derived from chitin, the most abundant biopolymer on the planet. It has shown potential among a wide variety of biomedical applications especially within the context of self-assembling nanocarriers usable in biomedical applications such as drug delivery, macroscopic injectables, tissue-engineering scaffolds, and nano-imaging agents. To date, many reviews have been focused on the biomedical properties and applications of CS-based nanocarriers, but a review is lacking on the role and prospects of different factors such as formulation parameters and preparation conditions on the properties of amphiphilic chitosan nanocarriers (ACNs) that have shown critical value in advancing drug delivery., (Copyright © 2017 Elsevier B.V. All rights reserved.)