Dual pH-responsive mesoporous silica nanoparticles for efficient combination of chemotherapy and photodynamic therapy

被引:59
作者
Yao, Xuemei [1 ]
Chen, Xiaofei [1 ]
He, Chaoliang [2 ]
Chen, Li [1 ]
Chen, Xuesi [2 ]
机构
[1] NE Normal Univ, Dept Chem, Changchun 130024, Peoples R China
[2] Chinese Acad Sci, Changchun Inst Appl Chem, Changchun 130022, Peoples R China
基金
中国国家自然科学基金;
关键词
DRUG-DELIVERY; CONTROLLED-RELEASE; IN-VITRO; CANCER-THERAPY; ACID; POLYMER; ACCUMULATION; NANOVEHICLES; AGGREGATION; PARTICLES;
D O I
10.1039/c5tb00256g
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
A kind of dual pH-responsive mesoporous silica nanoparticle (MSN)-based drug delivery system, which can respond to the cancer extracellular and intercellular pH stimuli, has been fabricated for synergistic chemo-photodynamic therapy. By grafting histidine onto the silica surface, the acid sensitive PEGylated tetraphenylporphyrin zinc (Zn-Por-CA-PEG) can be used as a gatekeeper to block the nanopores of MSNs by the metallo-supramolecular-coordinated interaction between Zn-Por and histidine. This gatekeeper is stable enough to prevent the loaded drug from leaching out in healthy tissue. However, at cancer extracellular pH (B6.8) the conjugated acid sensitive cis-aconitic anhydride ( CA) between Zn-Por and PEG will cleave and the surface of Zn-Por will be amino positively charged to facilitate cell internalization. Furthermore, the metallo-supramolecular-coordination will disassemble in intracellular acidic microenvironments (B5.3) to release the carried drug and Zn-Por due to the removal of the gatekeeper. The photosensitivity of Zn-Por further makes it possible to combine chemotherapy and photodynamic therapy. This dual pH-sensitive MSN-based drug delivery system showed higher in vitro cytotoxicity than the single chemotherapy of free DOX or photodynamic therapy of Zn-Por, presenting its great potential for cancer treatment to overcome the challenges in efficient delivery in the site and ideal anti-cancer efficacy.
引用
收藏
页码:4707 / 4714
页数:8
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