Targeted polymeric therapeutic nanoparticles: Design and interactions with hepatocellular carcinoma.
Nanoparticles (NPs) have great potential as drug delivery systems or as drugs for treating certain diseases. We designed three NPs with different charges and modifications with PEG to treat tumors. PDLA-CS, PEG-PLGA-PLL, and PEG-PS/CaP NPs were designed and evaluated to assess NPs fate in vivo and efficacy for treating tumors. Comparison between PEG-modified and non-PEG-modified NPs showed that PEG-modified NPs increased K(+) efflux, easily escaped from lysosomes, affected the mitochondria, induced mitochondrial apoptosis, had longer circulation time, and easily targeted tumors. Non-PEG-modified NPs induce the endoplasmic reticulum apoptosis pathway. Comparison between positively and negatively charged NPs showed that negatively charged NPs have less effect on the K(+) efflux of normal cells and more effect on the mitochondrial apoptosis of tumor cells. Positively charged NPs accumulated within the tumors and the liver and lungs. These results provide a theoretical basis for future clinical applications.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China; Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China.
Qi
Q
Wang
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China.
Ying
Y
Sun
Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: zrzzl@vip.sina.com.
Zhirong
Z
Zhang
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China. Electronic address: yrduan@shsmu.edu.cn.
Yourong
Y
Duan
D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000628:therapy*; D008247:Lysosomes / Q000737:chemistry; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D049268:Positron-Emission Tomography; D011188:Potassium / Q000737:chemistry; D014018:Tissue Distribution
D011108:Polymers; D011092:Polyethylene Glycols; D011188:Potassium
Apoptosis pathway; Cell membrane potential; Liver tumors; Polymeric therapeutic nanoparticles