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Programmed packaging of mesoporous silica nanocarriers for matrix metalloprotease 2-triggered tumor targeting and release
- Source :
- Biomaterials. 58:35-45
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
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.
- Subjects :
- Male
food.ingredient
Materials science
Biophysics
Antineoplastic Agents
Bioengineering
Nanotechnology
Ligands
Endocytosis
Gelatin
Cell Line
Biomaterials
Mice
Folic Acid
food
Microscopy, Electron, Transmission
In vivo
Cell Line, Tumor
Neoplasms
PEG ratio
medicine
Animals
Humans
Doxorubicin
Drug Carriers
Mice, Inbred BALB C
Neoplasms, Experimental
Mesoporous silica
Silicon Dioxide
Liver
Mechanics of Materials
Culture Media, Conditioned
Ceramics and Composites
Matrix Metalloproteinase 2
Nanoparticles
Nanocarriers
Mesoporous material
HT29 Cells
Neoplasm Transplantation
medicine.drug
Subjects
Details
- ISSN :
- 01429612
- Volume :
- 58
- Database :
- OpenAIRE
- Journal :
- Biomaterials
- Accession number :
- edsair.doi.dedup.....1b034b2f46562d9d0501f1ea52659916