Hydrazided hyaluronan/cisplatin/indocyanine green coordination nanoprodrug for photodynamic chemotherapy in liver cancer
Hydrazided hyaluronan/cisplatin/indocyanine green coordination nanoprodrug for photodynamic chemotherapy in liver cancer
复制标题
DOI：
10.1016/j.carbpol.2021.118810
复制
发表时间：
2021-10-29
影响因子：
11.2
通讯作者：
Suo, Aili
中科院分区：
文献类型：
--
作者：
Hou, Guanghui;Qian, Junmin;Suo, Aili
由于化疗药物和光敏剂的不同理化性质和药代动力学，通过刺激响应性连接将它们同时高效负载到单个纳米载体中仍然是一个巨大的挑战。本文基于顺铂-酰肼和顺铂-吲哚菁绿色（ICG）独特配位反应的发现，采用去溶剂化-双配位过程，制备了一种多功能配位纳米前药--顺铂/ICG共载酰肼化透明质酸/牛血清白蛋白（HBCI）纳米粒。该纳米前药表现出超高的载药效率和谷胱甘肽/近红外光双响应药物释放行为。体外细胞研究证明了纳米前药在HepG 2细胞中的有效内化和诱导凋亡的能力。体内试验结果证实了HBCI纳米前药的有效肿瘤蓄积和生物安全性以及基于HBCI的联合光动力化疗对抑制肿瘤生长的协同作用。总的来说，这项工作不仅为高效负载顺铂和ICG提供了一种新的双重协调方法，而且还验证了HBCI纳米前药在对抗肝细胞癌中的治疗潜力。
It is still a huge challenge for concurrent highly efficient loading of chemotherapeutic agent and photosensitizer into single nanocarrier via stimuli-responsive linkages due to their different physicochemical properties and pharmacokinetics. Herein, based on the discovery of unique cisplatin-hydrazide and cisplatin-indocyanine green (ICG) coordination reactions, a multifunctional coordination nanoprodrug, cisplatin/ICG co-loaded hydrazided hyaluronan/bovine serum albumin (HBCI) nanoparticles, was developed by a desolvation-dual coordination process. The nanoprodrug exhibited ultrahigh drug loading efficiency and glutathione/NIR light dual-responsive drug release behavior. In vitro cellular studies demonstrated efficient internalization and apoptosis-inducing ability of the nanoprodrug in HepG2 cells. In vivo results confirmed the efficacious tumor accumulation and biosafety of HBCI nanoprodrug and synergistic effect of HBCI-based combined photodynamic chemotherapy on inhibiting tumor growth. Overall, this work not only provides a novel dual coordination approach for highly efficient loading of cisplatin and ICG but also verifies the therapeutic potential of HBCI nanoprodrug in combating hepatocellular carcinoma.