Injectable Thermosensitive Polypeptide-Based CDDP-Complexed Hydrogel for Improving Localized Antitumor Efficacy

Abstract

In this study, a type of novel thermosensitive polypeptide-based hydrogel with tunable gelation behavior through changing the content of carboxyl groups was developed for the purpose of improving the cisplatin (CDDP) release behavior and enhancing the localized antitumor efficiency. The introduction of carboxyl groups in methoxy-poly(ethylene glycol)-b-(poly(γ-ethyl-l-glutamate-co-l-glutamic acid) (mPEG-b-P(ELG-co-LG)) not only led to adjustable mechanical properties of the hydrogel but also significantly reduced the burst release of the drug through the complexation between the carboxyl groups of polypeptide and CDDP. Furthermore, both the good biocompatibility and the biodegradable properties of mPEG-b-P(ELG-co-LG) hydrogel were observed in vivo. Interestingly, the CDDP-complexed mPEG-b-P(ELG-co-LG) hydrogel exhibited significantly enhanced antitumor efficacy in vivo compared to the mPEG-b-PELG hydrogel loaded with CDDP without complexation, although a lower cytotoxicity and IC of the CDDP-complexed hydrogel was observed in vitro. Overall, the new type of injectable CDDP-complexed hydrogel may serve as an efficient platform for sustained CDDP delivery in localized tumor therapy.

Thermosensitive Polypeptide Hydrogels Co‐Loaded with Two Anti‐Tumor Agents to Reduce Multi‐Drug Resistance and Enhance Local Tumor Treatment

“…No obvious edema, necrosis, hemorrhage, hyperemia, or muscle damage was observed throughout the experiments, suggesting that the hydrogels were well‐tolerated by the surrounding tissues. [ 43 ]…”

Recent progress in nanotechnology-based novel drug delivery systems in designing of cisplatin for cancer therapy: an overview

“…The mechanism behind to explain the improved anti-cancer efficacy of hydrogels based on depicting more sustained release of cisplatin from hydrogels. [131]. Dual drug CDDP/ PTX-loaded injectable hydrogel was developed for the treatment of ovarian cancer.…”

NIR-II light-modulated thermosensitive hydrogel for light-triggered cisplatin release and repeatable chemo-photothermal therapy

“…Cisplatin ( cis -diamminedichloroplatinum( ii ), denoted as CDDP) is one of the most effective chemotherapeutic agents for the treatment of various cancers, although its clinical use is limited by severe renal toxicity and chemoresistance 1–6. Effective accumulation of drugs in target sites at a sufficiently high concentration with less nonspecific distribution to normal organs is crucial for the clinical application of cisplatin, as well as for the other anticancer drugs 4–8. Spatially and temporally controlled delivery of therapeutic agents could improve the cisplatin release to tumor sites, and therefore would enhance its antitumor efficiency and minimize its off-target toxicity 4–7.…”

“…Effective accumulation of drugs in target sites at a sufficiently high concentration with less nonspecific distribution to normal organs is crucial for the clinical application of cisplatin, as well as for the other anticancer drugs 4–8. Spatially and temporally controlled delivery of therapeutic agents could improve the cisplatin release to tumor sites, and therefore would enhance its antitumor efficiency and minimize its off-target toxicity 4–7. Moreover, owing to the aggressive and resistant nature of cancer, the complete eradication of cancer by using chemotherapy alone remains a challenge.…”