Enhanced Drug Delivery by Nanoscale Integration of a Nitric Oxide Donor To Induce Tumor Collagen Depletion
Enhanced Drug Delivery by Nanoscale Integration of a Nitric Oxide Donor To Induce Tumor Collagen Depletion
复制标题
通过一氧化氮供体的纳米级整合增强药物输送以诱导肿瘤胶原蛋白消耗。
DOI：
10.1021/acs.nanolett.8b04236
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发表时间：
2019-02-01
期刊：
影响因子：
10.8
通讯作者：
Fang, Chao
中科院分区：
文献类型：
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作者：
Dong, Xiao;Liu, Hai-Jun;Fang, Chao
将治疗药物输送到固体肿瘤微环境是癌症纳米药物面临的主要挑战。给予某些外源性酶来消耗肿瘤间质成分已被认为是改善药物输送的一种方法。在这里，我们提出了一种无蛋白的胶原蛋白耗竭策略，用于实体瘤的药物输送，其基础是利用一氧化氮(NO)激活内源性基质金属蛋白酶(MMP1和MMP2)。将化疗药物阿霉素(DOX)和一氧化氮供体(S-亚硝硫醇)负载到介孔二氧化硅纳米粒(MSN)中，制备了dN@MSN。负载的NO导致MMPs的激活，MMPs降解肿瘤细胞外基质中的胶原。给予DN@MSN可增强纳米载体和货物(DOX)的肿瘤穿透性，从而显著提高抗肿瘤效果，且未观察到明显的毒性。
Delivery of therapeutics into the solid tumor microenvironment is a major challenge for cancer nanomedicine. Administration of certain exogenous enzymes which deplete tumor stromal components has been proposed as a method to improve drug delivery. Here we present a protein-free collagen depletion strategy for drug delivery into solid tumors, based on activating endogenous matrix metalloproteinases (MMP-1 and -2) using nitric oxide (NO). Mesoporous silica nanoparticles (MSN) were loaded with a chemotherapeutic agent, doxorubicin (DOX) as well as a NO donor (S-nitrosothiol) to create DN@MSN. The loaded NO results in activation of MMPs which degrade collagen in the tumor extracellular matrix. Administration of DN@MSN resulted in enhanced tumor penetration of both the nanovehicle and cargo (DOX), leading to significantly improved antitumor efficacy with no overt toxicity observed.