{'fraction_non_alphanumeric': 0.03316510454217736, 'fraction_numerical': 0.01658255227108868, 'mean_word_length': 5.871287128712871, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Thermosensitive Polypeptide Hydrogels Co‐Loaded with Two Anti‐Tumor Agents to Reduce Multi‐Drug Resistance and Enhance Local Tumor Treatment

Localized tumor treatment with hydrogels co‐loaded with two or more drugs is an emerging approach offering superior anti‐tumor efficacy and reduced systemic toxicity. Nevertheless, the development of multi‐drug resistance (MDR) during sustained local treatment with hydrogel depots has not been studied. In this study, a strategy is developed for local tumor combination therapy using a polypeptide hydrogel co‐loaded with doxorubicin (DOX) and cisplatin (CDDP) for evaluation in both drug‐sensitive A549 and CDDP‐resistant A549 (A549/CDDP) tumor models. It is found that the combination of DOX and CDDP synergistically inhibits both A549 and A549/CDDP cells in vitro, accompanying increased inhibition of the expression of the MDR and anti‐apoptosis B‐cell lymphoma 2 (Bcl‐2) genes. After a single peritumoral injection into nude mice bearing A549 or A549/CDDP xenografts, the DOX/CDDP co‐loaded hydrogels exhibit remarkably high anti‐tumor efficiency, compared with a dual‐drug solution or single drug‐loaded hydrogels. The development of MDR genes in both tumor models is inhibited by the hydrogel‐based combination therapy. This study presents an efficient strategy for long‐acting treatment of both drug‐sensitive and drug‐resistant tumors.