Local delivery of tumor‐targeting nano‐micelles harboring GSH‐responsive drug release to improve antitumor efficiency

Abstract

Increasing the accumulation of therapeutics in tumor site and improving the bioavailability of delivered drug are vital strategies to enhance chemotherapy efficiency as well as reduce side effects. Herein, we report an injectable hydrogel system to locally deliver tumor‐targeting nano‐micelles with GSH‐responsive drug release to improve antitumor efficiency. Amphiphilic polymers with different functions were designed and successfully synthesized. Then, the prepared polymers self‐assembled into nano‐micelles (PPR‐NP), which exhibited tumor cell targeting and GSH‐responsive drug release behavior. Furthermore, we constructed an injectable hydrogel system composed of the nano‐micelles (PPR‐NP@α‐CDgel). Peritumorally administrated to tumor site, PPR‐NP@α‐CDgel sustainedly released PPR‐NP around tumor site in situ, which were specifically taken up by tumor cells and rapidly released loaded paclitaxel in responsible to the high concentration of GSH in tumor cell, thus effectively inhibiting tumor growth. Synergized by the multitargeting effect, the present system could effectively improve the bioavailability of antineoplastic drug and enhance the antitumor efficiency, holding potential for solid tumor therapy.

Advancements and Applications of Injectable Hydrogel Composites in Biomedical Research and Therapy

“…pH-and temperature-responsive hydrogels incorporating chondroitin sulfate nanogels have exhibited selective binding to lung carcinoma cells and effective inhibition of cancer cell growth [41]. Injectable hydrogel systems equipped with tumor-targeting nano-micelles and glutathione-responsive drug release have demonstrated significant tumor growth inhibition and enhanced antitumor efficacy [56]. These examples underscore the potential of hydrogel-based drug delivery systems in the realm of cancer treatment.…”

“…The literature review highlights several significant trends and perspectives in the fields of drug delivery, tissue engineering, wound healing, cancer therapy, and therapeutic applications of injectable hydrogel systems. Injectable hydrogels have gained popularity as versatile platforms for drug delivery due to their gelation upon injection, which enables localized and sustained drug release [4,55,56,60,63,64,[73][74][75][76][77][78]80,103]. Achieving targeted and localized drug delivery to specific sites, such as tumor cells or pathological areas, has been a major focus of research, and various strategies have been explored to achieve this objective [40,41,59,62,73,75,77].…”

Recent Advances in Polycaprolactones for Anticancer Drug Delivery

“…Li et al [ 174 ] designed an injectable hydrogel, poly(ethylene glycol)- b -poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) that can be triggered by GSH to locally deliver PTX into tumor sites. In the presence of GSH, about 70% PTX was released at pH (7.4) and only 40% without GSH.…”

Thermo-Sensitive Nanoparticle-Hydrogel Composite Based on Pluronic F127 and Phycocyanin for an Enhanced Chemo-Photodynamic Antitumor Effect

“…22 Currently, local drug delivery systems demonstrate benefits in terms of tumor drug accumulation and regulated drug release. 23,24 Among them, localized drug delivery platforms have the capability to establish drug reservoirs at the tumor area, enabling sustained and controlled release of loaded drugs over an extended duration. As a result, these systems effectively impede tumor growth.…”

“…Numerous nano-drug delivery systems (NDDS), including nanoliposomes and nano-hydrogels, have been created in recent years to deliver chemotherapy medicines and photosensitizers to tumors. − NDDSs can significantly improve the tumor-targeting efficiency of loaded drugs, enhance selectivity, reduce side effects, and improve the efficacy of combination therapy. − Nevertheless, intravenous NDDSs are susceptible to various issues: including untimely drug release, unsynchronized targeting, dosage constraints, and potential immunotoxicity related to carrier materials . Currently, local drug delivery systems demonstrate benefits in terms of tumor drug accumulation and regulated drug release. , Among them, localized drug delivery platforms have the capability to establish drug reservoirs at the tumor area, enabling sustained and controlled release of loaded drugs over an extended duration. As a result, these systems effectively impede tumor growth. , In situ hydrogels, especially temperature-sensitive hydrogels, have good fluidity and can be directly injected into or around tumors. − The transformation from liquid to gel under the action of body temperature can well cover the tumor tissue on the one hand and prolong the local residence time of the drug on the other hand, forming a high-concentration drug reservoir. , Therefore, local drug delivery systems combining injectable hydrogels with nanomedicines are expected to produce synergistic effects, which are of great significance for tumor therapy. ,, …”