title: Lipid-polymer nanoparticles encapsulating doxorubicin and 2'-deoxy-5-azacytidine enhance the sensitivity of cancer cells to chemical therapeutics.
abstract: Nanomedcine holds great potential in cancer therapy due to its flexibility on drug delivery, protection, releasing, and targeting. Epigenetic drugs, such as 2'-deoxy-5-azacytidine (DAC), are able to cause reactive expression of tumor suppressor genes (TSG) in human cancers and, therefore, might be able to enhance the sensitivity of cancer cells to chemotherapy. In this report, we fabricated a lipid-polymer nanoparticle for codelivery of epigenetic drug DAC and traditional chemotherapeutic drug (DOX) to cancer cells and monitored the growth inhibition of the hybrid nanoparticles (NPs) on cancer cells. Our results showed that NPs encapsulating DAC, DOX, or both, could be effectively internalized by cancer cells. More importantly, incorporating DAC into NPs significantly enhanced the sensitivity of cancer cells to DOX by inhibiting cell growth rate and inducing cell apoptosis. Further evidence indicated that DAC encapsulated by NPs was able to rescue the expression of silenced TSG in cancer cells. Overall our work clearly suggested that the resulting lipid-polymer nanoparticle is a potential tool for combining epigenetic therapy and chemotherapy.
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Shenzhen Key Laboratory of Cancer Nanotechnology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P. R. China.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Su
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Mingbin
authors.initials: M
authors.lastname: Zheng
authors.forename: Cuifang
authors.initials: C
authors.lastname: Zheng
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhao
authors.forename: Yifan
authors.initials: Y
authors.lastname: Ma
authors.forename: Qian
authors.initials: Q
authors.lastname: Tao
authors.forename: Lintao
authors.initials: L
authors.lastname: Cai
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077209:Decitabine; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004357:Drug Synergism; D044127:Epigenesis, Genetic / Q000187:drug effects; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000970:Antineoplastic Agents; D053769:Nanocapsules; D010714:Phosphatidylethanolamines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D000077209:Decitabine; D004317:Doxorubicin; D001374:Azacitidine