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Not AvaStimuli-responsive polypeptides offer unique advantages for biomedical applications due to their biocompatibility, degradability, and structural tunability. In this study, we report the synthesis of innovative redox-responsive polypeptide-based diblock copolymers consisting of functional disulfide-containing homocysteine derivatives and hydrophobic γ-benzyl-l-glutamate segments via sequential ring-opening polymerizations. The polymerization kinetics revealed that the polymerizations were well-controlled with living characteristics, resulting in diblock copolymers PHcy-b-PBLG with narrow molecular weight distributions. The resulting functional-hydrophobic diblock copolymers were further converted to a variety of pendant chains via thiol–disulfide exchange reactions, yielding amphiphilic polymers with tunable surface charges. These disulfide-linked materials readily self-assembled into nanoparticles in aqueous environments with hydrophobic PBLG forming the core and redox-sensitive PHcy forming the shell. The redox-responsive nanoparticles displayed a narrow size distribution, excellent colloidal stability, and excellent biocompatibility. The disulfide bonds within the polymer backbone confer redox sensitivity, allowing potential cleavage in reducing environments. Owing to their tunable surface functionality, redox-responsiveness, and biocompatibility, this platform provides a versatile route to engineer responsive nanostructures for biomedical applications, for example, positively charged nanoparticles toward nucleic acid delivery.ilable 

Proteolysis-targeting chimera (PROTAC) has emerged as a groundbreaking therapeutic strategy by hijacking the endogenous ubiquitin proteasome system (UPS) for targeted protein degradation. These heterobifunctional molecules recruit E3 ligases to recognize the protein of interest (POI) and facilitate its ubiquitination, leading to subsequent proteasomal degradation. Compared to conventional protein inhibitors, PROTACs offer a broader range of target degradation and remain effective even against proteins with drug-resistant mutations. Moreover, PROTACs function in a catalytic manner to degrade POIs, allowing for significantly lower administration dosages. In recent years, PROTACs have shown great promise in cancer therapy due to their high efficiency and broad applicability. However, their clinical applications remain challenging due to low bioavailability, limited tumor-targeting ability, and potential side effects. Utilizing nanomedicine for the delivery of PROTACs offers a promising strategy to enhance bioavailability, improve tumor selectivity, and minimize toxicity, thereby advancing their applications in cancer treatment. In this review, we outline the fundamental design principles of PROTACs, summarize the latest progress of nanomedicines from molecular design to drug delivery for improved tumor treatment, introduce PROTAC-based combination therapies and emerging design strategies, and discuss current challenges and future prospects of PROTAC nanomedicines toward clinical translation. 

Not AvaDisulfide-containing synthetic polypeptides hold significant promise as biodegradable and biocompatible carriers for controlled drug and gene delivery, enabling triggered therapeutic release with reduced cytotoxicity. However, disulfide incorporation remains challenging, whether through direct polymerization of disulfide-containing monomers or postpolymerization modification. In this work, we present an innovative and simple strategy to incorporate disulfide bonds into polypeptides using ring-opening polymerization of the N-carboxyanhydride of homocysteine, a thiol-containing amino acid. The polymerization was well-controlled, yielding repeating units up to 100 with narrow dispersity. The pendant side chains were readily converted into various GSH-responsive moieties, including anionic, neutral, zwitterionic, and cationic groups, as well as therapeutic agents toward a wide range of biomedical applications. The drug-loaded amphiphilic polymer-drug conjugates displayed triggered release of intact drug and potent anticancer activities. Furthermore, cationic polyhomocysteine derivatives effectively delivered siRNA, eGFP mRNA, and more complex CRISPR components with extremely low cytotoxicity and excellent transfection efficiency.ilable 

Not AvSelf-assembled polymeric micelles formed from amphiphilic block copolymers offer a promising strategy for enhanced drug delivery due to their biocompatibility and controlled release. However, challenges such as their poor colloidal stability under diluted conditions and degradation during storage and circulation limit their further applications. To address these issues, we developed a straightforward method for constructing cross-linked polycarbonate micelles that enhance stability while allowing for controlled stimuli-responsive drug delivery. By utilizing disulfide-based cross-linking and covalent conjugation of the anticancer drug, our approach maintains micelle integrity and extremely high drug loading over extended periods as well as the superior control of triggered drug release compared to non-cross-linked versions, demonstrating enhanced stability in complex biological environments and improved anticancer efficacy, presenting a novel platform for stable polymer–drug conjugate nanocarriers, holding significant therapeutic potential for targeted cancer treatment. 

A novel drug delivery system hitchhiking albumin as a drug carrier with tuneable redox-responsive drug release. 

Messenger RNA (mRNA)-based therapeutic agents have demonstrated significant potential in recent times, particularly in the context of the COVID-19 pandemic outbreak. As a promising prophylactic and therapeutic strategy, polypeptide-based mRNA... 

Biodegradable and adaptable polymeric materials are currently being studied due to their wide scope of potential applications, from nanomedicine to novel multifunctional materials. One such class of polymers are poly(disulfide)s, which contain repeating disulfide bonds in their main chain. Lipoic acid, or thioctic acid, is a biologically derived small molecule containing a 1,2-dithiolane ring capable of undergoing ring opening polymerization to yield poly(disulfide)s. In this review, we highlight the synthesis of lipoic acid-based poly(disulfide)s through thermal and thiolate-initiated ring opening polymerizations, and the development of methodology pertaining to the synthetic methods. We further discuss the biomedical applications of poly(disulfide)s, which have been widely used to construct various responsive biomaterials, including polymer-drug conjugates, nanoparticles, hydrogels, and adhesives.