Self‐Amplifying Nanotherapeutic Drugs Homing to Tumors in a Manner of Chain Reaction

癌症研究 结合 化学 药理学 医学 数学 数学分析
作者
Yue Wang,Na Shen,Ying Wang,Yu Zhang,Zhaohui Tang,Xuesi Chen
出处
期刊:Advanced Materials [Wiley]
卷期号:33 (7) 被引量:28
标识
DOI:10.1002/adma.202002094
摘要

Abstract Active tumor‐targeting drug delivery has great potency in cancer therapy. However, the targeting efficiency of traditional active tumor‐targeting nanotherapeutic drugs is limited by the scarcity of their accessible targets/receptors in tumors. Here, a novel self‐amplifying tumor‐targeting strategy with a chain reaction mechanism is developed. A coagulation targeting peptide (GNQEQVSPLTLLKXC, termed A15)‐decorated poly(L‐glutamic acid)‐ graft ‐maleimide poly(ethylene glycol)/combretastatin A4 conjugate (A15‐PLG‐CA4) is prepared to obtain a self‐amplifying nanotherapeutic platform homing to tumors. After administration to tumor‐bearing mice, A15‐PLG‐CA4 starts a chain reaction cycle consisting of intratumoral hemorrhage, target FXIIIa amplification, blood clot binding, and CA4 release in tumors. In this way, A15‐PLG‐CA4 increases the level of its accessible targets (FXIIIa) in a manner of chain reaction. The FXIIIa activity at 8 h is 4.1‐fold more than the one at 0 h in the C26 tumors treated with A15‐PLG‐CA4. The total CA4 concentration at 24 h is 2.9‐fold more than the control. A15‐PLG‐CA4 shows a significantly higher antitumor effect against large C26 tumors (≈500 mm 3 ) thanks to the remarkable tumor‐targeting ability compared with the control. Therefore, this report highlights the potential of the self‐amplifying tumor‐targeting strategy in the development of next generation active tumor‐targeting nanotherapeutic drugs for tumor therapy.
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