Programmed packaging of mesoporous silica nanocarriers for matrix metalloprotease 2-triggered tumor targeting and release.
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.
College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China.
Zhen
Z
Zou
College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China. Electronic address: xiaoxiaohe@hnu.edu.cn.
Xiaoxiao
X
He
College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China.
Dinggeng
D
He
College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China. Electronic address: kmwang@hnu.edu.cn.
Kemin
K
Wang
College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China.
Zhihe
Z
Qing
College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China.
Xue
X
Yang
College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China.
Li
L
Wen
College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China.
Jun
J
Xiong
College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China.
Liling
L
Li
College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China.
Linli
L
Cai
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002460:Cell Line; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D004705:Endocytosis; D005492:Folic Acid / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D008024:Ligands; D008099:Liver / Q000166:cytology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D009374:Neoplasms, Experimental / Q000188:drug therapy; D012822:Silicon Dioxide / Q000737:chemistry*
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D004337:Drug Carriers; D008024:Ligands; D012822:Silicon Dioxide; D004317:Doxorubicin; D005780:Gelatin; D005492:Folic Acid; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
Gelatin; Matrix metalloproteinases 2; PEG deshielding; Programmed packaging; Tumor targeting