Photosensitizer-Loaded Branched Polyethylenimine-PEGylated Ceria Nanoparticles for Imaging-Guided Synchronous Photochemotherapy.
A multifunctional theranostic platform based on photosensitizer (chlorin e6, Ce6)-loaded branched polyethylenimine-PEGylated ceria nanoparticles (PPCNPs-Ce6) was created for the development of effective cancer treatments involving the use of imaging-guided synchronous photochemotherapy. PPCNPs-Ce6 with high Ce6 photosensitizer loading (Ce6: cerium ∼40 wt %) significantly enhanced the delivery of Ce6 into cells and its accumulation in lysosomes, remarkably improving photodynamic therapeutic (PDT) efficacy levels compared to those in the administration of free Ce6 at ultralow drug doses (∼200 nM). Interestingly, PPCNPs-Ce6 efficiently induced HeLa cell death even at low concentrations (∼10 μM) without the use of laser irradiation and exhibit chemocytotoxicity. Inductively coupled plasma mass spectrometry (ICP-MS) and biology transmission electron microscopy (Bio-TEM) analyses demonstrated that ceria nanoparticles enter cells abundantly and accumulate in lysosomes or large vesicles. We then evaluated the effects of the different materials on lysosomal integrity and function, which revealed that PPCNPs-Ce6 catastrophically impaired lysosomal function compared to results with PPCNPs and Ce6. Studies of apoptosis revealed greater induction of apoptosis by PPCNPs-Ce6 treatment. This multifunctional nanocarrier also exhibited a high degree of solubility and stability in aqueous solutions, suggesting its applicability for extensive biomedical application.
State Key Laboratory of Trauma Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Zhang-You
ZY
Yang
State Key Laboratory of Trauma Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Hong
H
Li
State Key Laboratory of Trauma Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Yi-Ping
YP
Zeng
State Key Laboratory of Trauma Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Yu-Hui
YH
Hao
State Key Laboratory of Trauma Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Cong
C
Liu
State Key Laboratory of Trauma Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Jing
J
Liu
Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Wei-Dong
WD
Wang
State Key Laboratory of Trauma Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Rong
R
Li
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001672:Biocompatible Materials / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival; D002563:Cerium / Q000737:chemistry*; D002735:Chlorophyllides; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007834:Lasers; D008247:Lysosomes / Q000737:chemistry; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; D049452:Green Fluorescent Proteins; D002563:Cerium; D011092:Polyethylene Glycols; C062985:phytochlorin; D011094:Polyethyleneimine
ceria nanoparticles; imaging-guided; lysosome-targeted; photochemotherapy; synchronous