期刊
NANO LETTERS
卷 19, 期 2, 页码 997-1008出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.8b04236
关键词
Nitric oxide; nanoparticles; tumor penetration; collagen depletion; matrix metalloproteinase
类别
资金
- National Natural Science Foundation of China [81572998, 81773274]
- Shanghai Municipal Science and Technology Commission [16520710700]
- Shu Guang Program of Shanghai Education Development Foundation
- Shanghai Municipal Education Commission [165G13]
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.
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