Naphthalocyanine-Based Biodegradable Polymeric Nanoparticles for Image-Guided Combinatorial Phototherapy
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文摘
Image-guided phototherapy is extensively considered as a promising therapy for cancer treatment. To enhance translational potential of this modality, we developed a single agent-based biocompatible nanoplatform that provides both real time near-infrared (NIR) fluorescence imaging and combinatorial phototherapy with dual photothermal and photodynamic therapeutic mechanisms. The developed theranostic nanoplatform consists of two building blocks: (1) silicon naphthalocyanine (SiNc) as a NIR fluorescence imaging and phototherapeutic agent and (2) a copolymer, poly(ethylene glycol)-block-poly(蔚-caprolactone) (PEG鈥揚CL) as the biodegradable SiNc carrier. Our simple, highly reproducible, and robust approach results in preparation of spherical, monodisperse SiNc-loaded PEG鈥揚CL polymeric nanoparticles (SiNc-PNP) with a hydrodynamic size of 37.66 卤 0.26 nm (polydispersity index = 0.06) and surface charge of 鈭?.76 卤 1.83 mV. The SiNc-loaded nanoparticles exhibit a strong NIR light absorption with an extinction coefficient of 2.8 脳 105 M鈥? cm鈥? and efficiently convert the absorbed energy into fluorescence emission (桅F = 11.8%), heat (螖T 鈭?25 掳C), and reactive oxygen species. Moreover, the SiNc-PNP are characterized by superior photostability under extensive photoirradiation and structure integrity during storage at room temperature over a period of 30 days. Following intravenous injection, the SiNc-PNP accumulated selectively in tumors and provided high lesion-to-normal tissue contrast for sensitive fluorescence detection. Finally, adriamycin-resistant tumors treated with a single intravenous dose of SiNc-PNP (1.5 mg/kg) combined with 10 min of a 785 nm light irradiation (1.3 W/cm2) were completely eradicated from the mice without cancer recurrence or side effects. The reported characteristics make the developed SiNc-PNP a promising platform for future clinical application.

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