一种多模态治疗性纳米制剂，可显著增强多西他赛治疗去势抵抗性前列腺癌的疗效。
A Multimodal Theranostic Nanoformulation That Dramatically Enhances Docetaxel Efficacy Against Castration Resistant Prostate Cancer.
机构信息
Institute for Lasers, Photonics and Biophotonics, Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, New York 14260.
Institute for Lasers, Photonics and Biophotonics, Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, New York 14260; Division of Allergy, Immunology, and Rheumatology, Department of Medicine, State University of New York at Buffalo, Clinical Translational Research Center, Buffalo, New York 14203; Department of Anesthesiology, University at Buffalo, The State University of New York, Buffalo, New York 14203.
出版信息
J Pharm Sci. 2020 Sep;109(9):2874-2883. doi: 10.1016/j.xphs.2020.06.004. Epub 2020 Jun 11.
In this work, a multifunctional hierarchical nanoformulation composed of biodegradable chitosan (CS) coated poly (lactic-co-glycolic acid) (PLGA) nanocarriers loaded with docetaxel (Doc) and interleukin-8 (IL-8) small interfering RNA (siRNA) electrostatically bound to upconversion nanoparticles (UCNPs), is developed to treat castration-resistant prostate cancer (CRPC). This theranostic nanoformulation facilitates simultaneous delivery of chemotherapy and gene therapy, as well as a bimodal optical and magnetic resonance imaging agent that could enable image-guided combination therapy. Poly-d-lysine coated NaYF; Yb20%, Er2%@NaYF; Gd50% core@shell UCNPs are effective siRNA transfection agents, and Er doping provides upconversion imaging capabilities, while Gd doping enables magnetic resonance contrast enhancement. These properties are maintained upon encapsulation in PLGA-CS. PLGA-CS nanocarriers containing Doc and UCNP-siRNA are 235 ± 5 nm with a zeta potential of +17 ± 4 meV, and have a high Doc encapsulation efficiency of 57 ± 6%. Compared to free Doc, this PLGA-CS nanoformulation containing Doc and UCNP-siRNA exhibits a dramatic decrease in IC of ~14,000 fold (p < 0.001) through combination therapy in human PC-3 prostate cancer cells. This biocompatible, multimodal, theranostic nanoformulation demonstrates paradigm-shifting enhancement in anticancer activity over free Doc, with unique potential for use in image-guided combination therapy to treat CRPC.
在这项工作中，开发了一种由可生物降解的壳聚糖（CS）包覆的载有多西紫杉醇（Doc）和白细胞介素-8（IL-8）小干扰 RNA（siRNA）的聚乳酸-共-羟基乙酸（PLGA）纳米载体组成的多功能分级纳米制剂，通过静电结合到上转换纳米粒子（UCNPs）上，用于治疗去势抵抗性前列腺癌（CRPC）。这种治疗诊断纳米制剂便于同时递送化疗和基因治疗，以及双模式光学和磁共振成像剂，可实现图像引导的联合治疗。聚-d-赖氨酸包覆的 NaYF; Yb20%，Er2%@NaYF; Gd50%核/壳 UCNPs 是有效的 siRNA 转染剂，而 Er 掺杂提供上转换成像能力，而 Gd 掺杂可增强磁共振对比。这些特性在封装到 PLGA-CS 中后得以保留。载有 Doc 和 UCNP-siRNA 的 PLGA-CS 纳米载体的粒径为 235±5nm，ζ电位为+17±4mV，Doc 包封效率高达 57±6%。与游离 Doc 相比，这种载有 Doc 和 UCNP-siRNA 的 PLGA-CS 纳米制剂在人 PC-3 前列腺癌细胞中的组合治疗下，IC50 降低了约 14000 倍（p<0.001）。这种生物相容性的多模态治疗诊断纳米制剂在抗癌活性方面表现出了对游离 Doc 的显著增强，具有独特的潜力，可用于图像引导的联合治疗来治疗 CRPC。
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