Journal
ACS NANO
Volume 9, Issue 1, Pages 991-1003Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn506963h
Keywords
nanoscale coordination polymer; core shell nanostructure; combination of chemotherapy and photodynamic therapy; tumor regression
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Funding
- National Cancer Institute [U01-CA151455]
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Combination therapy enhances anticancer efficacy of both drugs via synergistic effects. We report here nanoscale coordination polymer (NCP)-based coreshell 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 coreshell nanoparticles as a versatile and effective drug delivery system for potential translation to the clinic.
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