Low-molecular-weight polymer-drug conjugates for synergistic anticancer activity of camptothecin and doxorubicin combinations

低分子量聚合物-药物偶联物可增强喜树碱和阿霉素联合用药的抗癌协同作用

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Abstract

BACKGROUND: High-molecular-weight (MW) polymers (>50,000 Da) can be conjugated to chemotherapy drugs in order to improve their tumor accumulation, while low MW polymers ≤10,000 Da are often overlooked due to faster plasma clearance. Small polymers, however, may facilitate deeper tumor penetration. MATERIALS & METHODS: Here, we investigate the anticancer efficacy of 10 kDa hyaluronic acid or poly(vinyl alcohol) conjugated to synergistic combinations of camptothecin and doxorubicin, with emphasis on chemical linker impacts. RESULTS: Our results emphasize drug hydrolyzability for synergy preservation, and also demonstrate superior cancer cell inhibition with low MW polymer-drug conjugates. CONCLUSION: This study shows the high therapeutic potential of low MW polymer-drug conjugates for polychemotherapy delivery, and provides further insight into the development of polymer-drug therapeutics.

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