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

Tu, Jing, Wang, Tianxiao, Shi, Wei, Wu, Guisen, Tian, Xinhua, Wang, Yuhua, Ge, Dongtao, Ren, Lei
Biomaterials 2012 v.33 no.31 pp. 7903-7914
biocompatibility, cytosol, encapsulation, ethylene glycol, intravenous injection, lysosomes, membrane potential, mice, mitochondrial membrane, nanocarriers, nanoparticles, phototoxicity, silica, singlet oxygen, zinc
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.