title: Self-assembled core-shell nanoparticles for combined chemotherapy and photodynamic therapy of resistant head and neck cancers.
abstract: Combination therapy enhances anticancer efficacy of both drugs via synergistic effects. We report here nanoscale coordination polymer (NCP)-based core-shell nanoparticles carrying high payloads of cisplatin and the photosensitizer pyrolipid, NCP@pyrolipid, for combined chemotherapy and photodynamic therapy (PDT). NCP@pyrolipid releases cisplatin and pyrolipid in a triggered manner to synergistically induce cancer cell apoptosis and necrosis. In vivo pharmacokinetic and biodistribution studies in mice show prolonged blood circulation times, low uptake in normal organs, and high tumor accumulation of cisplatin and pyrolipid. Compared to monotherapy, NCP@pyrolipid shows superior potency and efficacy in tumor regression (83% reduction in tumor volume) at low drug doses in the cisplatin-resistant human head and neck cancer SQ20B xenograft murine model. We elucidated the in vitro/vivo fate of the lipid layer and its implications on the mechanisms of actions. This study suggests multifunctional NCP core-shell nanoparticles as a versatile and effective drug delivery system for potential translation to the clinic.
authors.affiliation: Department of Chemistry, University of Chicago , 929 E 57th Street, Chicago, Illinois 60637, United States.
authors.forename: Chunbai
authors.initials: C
authors.lastname: He
authors.forename: Demin
authors.initials: D
authors.lastname: Liu
authors.forename: Wenbin
authors.initials: W
authors.lastname: Lin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D003131:Combined Modality Therapy; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D006801:Humans; D051379:Mice; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D017319:Photosensitizing Agents; D011108:Polymers; D002945:Cisplatin
keywords: combination of chemotherapy and photodynamic therapy; core−shell nanostructure; nanoscale coordination polymer; tumor regression