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Programmed packaging of mesoporous silica nanocarriers for matrix metalloprotease 2-triggered tumor targeting and release.

Abstract：

:The development of multifunctional nanocarrier with each unit functioning at the correct time and location is a challenge for clinical applications. With this in mind, a type of intelligent mesoporous silica nanocarrier (PGFMSN) is proposed for matrix metalloprotease 2 (MMP 2)-triggered tumor targeting and release by integrating programmed packing and MMP 2-degradable gelatin. Mesoporous silica nanoparticles (MSN) are first functionalized with folic acid (FA) as a target ligand to improve cell uptake. Then gelatin is introduced onto FA-MSN via temperature-induced gelation, where gelatin layer blocks drugs inside the mesopores and protects the targeting ligand. To prolong blood-circulation lifetime, PEG is further decorated to obtain PGFMSN. All units are programmatically incorporated in a simple way and coordinated in an optimal fashion. Cells, multicellular spheroids and in vivo results demonstrate that PGFMSN is shielded against nonspecific uptake. After circulating to tumor tissue, the up-regulated MMP-2 hydrolyzes gelatin layer to deshield PEG and switch on the function of FA, which facilitate the selective uptake by tumor cells through folate-receptor-mediated endocytosis. Meanwhile, the packaged drug is released due to the shedding of gelatin layer. It is shown that doxorubicin (DOX)-loaded exhibits superior tumor targeting, drug internalization, cytotoxicity, and antitumor efficacy over free DOX, non-PEGylated and non-targeted nanoparticles, which provides potential applications for targeted cancer therapy.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Zou Z,He X,He D,Wang K,Qing Z,Yang X,Wen L,Xiong J,Li L,Cai L

doi

10.1016/j.biomaterials.2015.04.034

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

35-45

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(15)00389-0

journal_volume

58

pub_type

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