靶向光敏剂NaYF4:Yb,Tm@ NaGdF4:Yb@TiO2@PEI-PAA-FA的制备和性能

Preparation and Properties of Targeting Photosensitizer NaYF4:Yb,Tm@NaGdF4:Yb@TiO2@PEI-PAA-FA

摘要:

采用水解法对上转换纳米粒NaYF4:Yb,Tm@ NaGdF4:Yb包覆TiO2，然后修饰聚乙烯亚胺（PEI）和聚丙烯酸（PAA）并偶联叶酸（FA），制备了叶酸受体靶向纳米光敏剂（NaYF4:Yb,Tm@ NaGdF4:Yb@TiO2@PEI-PAA-FA）。借助XRD和TEM表征NaYF4:Yb,Tm@ NaGdF4:Yb@TiO2的物相和形貌，FTIR和ξ电位证实有机成分的修饰成功，并测试了产物的上转换发光光谱。在980 nm近红外光（NIR）下，纳米光敏剂存在下的1,3-二苯基异苯并呋喃溶液吸收光谱的降低证明了单线态氧的产生。此外，纳米光敏剂可以载带阿霉素（DOX），最大载药率为50.8%，包封率为84.7%。载药后的纳米光敏剂中DOX释放对介质具有pH响应性，在NIR照射的酸性介质（pH 5.0）中12 h的累积[累计还是累积？][累积]缓释率为38.1%，远高于中性介质（pH 7.4）的10.4%。结果表明，DOX负载和FA偶联的纳米光敏剂有望作为NIR驱动光动力治疗-化疗协同灭活肿瘤细胞的药物。

Abstract:

Folate receptor-targeted nanophotosensitizer (NaYF4:Yb,Tm@NaGdF4:Yb@TiO2 @PEI-PAA-FA) was prepared by coating TiO2 on the upconversion nanoparticles NaYF4:Yb,Tm@NaGdF4:Yb via a hydrolysis method, followed by modification with polyethyleneimine (PEI) and polyacrylic acid (PAA) and subsequent conjugation of folic acid (FA). XRD and TEM were used to characterize the crystal structure and morphology of the inorganic components of the nanophotosensitizer. FTIR and ξ potential were used to verify the binding of these organic components. Upconversion luminescence spectra of the samples were also measured. The decrease in the absorbance of 1,3-Diphenylisobenzofuran solution in the presence of the nanophotosensitizer under 980 nm near-infrared (NIR) laser irradiation indicated the singlet oxygen has been produced from the nanophotosensitizer. Besides, the photosensitizer has a doxorubicin (DOX) loading capacity, the maximum drug loading ratio was 50.8% and the encapsulation efficiency was 84.7%. The DOX release from the nanophotosensitizer was sensitive to the pH value of the buffer. As the DOX-loaded nanophotosensitizer was suspended in an acidic buffer of pH 5.0 and exposed to NIR laser irradiation, the cumulative release of DOX at 12 h was 38.1%, much higher than that obtained from a neutral buffer (pH 7.4), which was 10.4%. These results indicated the DOX-loaded and FA-coupled nanophotosensitizer may be a potential drug for synergistic inactivation of cancer cell by NIR-driven photodynamic therapeutic and chemotherapeutic modalities.