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Multifunctional ZnPc-loaded mesoporous silica nanoparticles for enhancement of photodynamic therapy efficacy by endolysosomal escape

Author:
Tu, Jing, Wang, Tianxiao, Shi, Wei, Wu, Guisen, Tian, Xinhua, Wang, Yuhua, Ge, Dongtao, Ren, Lei
Source:
Biomaterials 2012 v.33 no.31 pp. 7903-7914
ISSN:
0142-9612
Subject:
biocompatibility, cytosol, encapsulation, ethylene glycol, intravenous injection, lysosomes, membrane potential, mice, mitochondrial membrane, nanocarriers, nanoparticles, phototoxicity, silica, singlet oxygen, zinc
Abstract:
The cellular uptake and localization of photosensitizer-loaded nanoparticles have significant impact on photodynamic therapy (PDT) efficacy due to short lifetime and limited action radius of singlet oxygen. Herein, we develop poly(ethylene glycol) (PEG)- and polyethylenimine (PEI)-functionalized zinc(II) phthalocyanine (ZnPc)-loaded mesoporous silica nanoparticles (MSNs), which are able to distribute in the cytosol by endolysosomal escape. In this photosensitizer-carrier system (PEG–PEI–MSNs/ZnPc), ZnPc is a PDT agent; MSNs are the nanocarrier for encapsulating ZnPc; PEI facilitates endosomal escape; and PEG enhances biocompatibility. The as-synthesized PEG–PEI–MSNs/ZnPc have a high escape efficiency from the lysosome to the cytosol due to the “proton sponge” effect of PEI. Compared with the ZnPc-loaded MSNs, the phototoxicity of the PEG–PEI–MSNs/ZnPc is greatly enhanced in vitro. By measuring the mitochondrial membrane potential, a significant loss of >80% Δψm after treatment with PEG–PEI–MSNs/ZnPc–PDT is observed. It is further demonstrated that the ultra-efficient passive tumor targeting and excellent PDT efficacy are achieved in tumor-bearing mice upon intravenous injection of PEG–PEI–MSNs/ZnPc and the followed light exposure. We present here a strategy for enhancement of PDT efficacy by endolysosomal escape and highlight the promise of using multifunctional MSNs for cancer therapy.
Agid:
904557