title: Multifunctional ZnPc-loaded mesoporous silica nanoparticles for enhancement of photodynamic therapy efficacy by endolysosomal escape.
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.
authors: Department of Biomaterials/Biomedical Engineering Research Center, College of Materials, Xiamen University, Xiamen 361005, China.
authors: Jing
authors: J
authors: Tu
authors: Tianxiao
authors: T
authors: Wang
authors: Wei
authors: W
authors: Shi
authors: Guisen
authors: G
authors: Wu
authors: Xinhua
authors: X
authors: Tian
authors: Yuhua
authors: Y
authors: Wang
authors: Dongtao
authors: D
authors: Ge
authors: Lei
authors: L
authors: Ren
mesh_terms: D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D011992:Endosomes / Q000378:metabolism*; D005434:Flow Cytometry; D007211:Indoles / Q000737:chemistry*; D042541:Intracellular Space / Q000378:metabolism; D054833:Isoindoles; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009942:Organometallic Compounds / Q000737:chemistry*; D010778:Photochemotherapy / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000031:analogs & derivatives / Q000737:chemistry; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D014018:Tissue Distribution; D016896:Treatment Outcome; D017967:Zinc Compounds
chemical_list: D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017967:Zinc Compounds; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); C052159:Zn(II)-phthalocyanine; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D011094:Polyethyleneimine