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基于介孔铂纳米颗粒的纳米平台用于联合化疗-光热乳腺癌治疗。

Mesoporous platinum nanoparticle-based nanoplatforms for combined chemo-photothermal breast cancer therapy.

机构信息

Department of Radiology, Changhai Hospital, Navay Medical Univerisity, 200433 Shanghai, PR China.

Key Laboratory for Organic Electronics and Information Displays and Institute of Advanced Materials, Nanjing University of Posts and Telecommunications, Nanjing, 210046 Jiangsu, PR China.

出版信息

J Colloid Interface Sci. 2020 Jun 15;570:197-204. doi: 10.1016/j.jcis.2020.02.051. Epub 2020 Feb 17.

DOI:10.1016/j.jcis.2020.02.051
PMID:32151829
Abstract

High-efficiency cancer treatment remains the main challenge at present. In this study, a mesoporous platinum nanoparticle- (mesoPt) based nanoplatform is exported for effective tumor treatment, integrating computed tomography (CT) imaging, photothermal conversion, and chemotherapeutic drug delivery capabilities. Mesoporous platinum nanoparticles are facilely synthesized by using Pluronic F127 as a structure-directing agent without seeds or organic reagents and have a spherical structure and uniform diameter of 94 nm. The surface of the mesoPt is modified with polyethylene glycol (PEG), and the prepared mesoPt-PEG shows excellent biocompatibility. Doxorubicin (Dox)-loaded PEG@Pt (PEG@Pt/Dox) is further prepared by electrostatic adsorption and the drug-loading capacity is as high as 25%. In vitro studies demonstrate that Dox can be controllably released from PEG@Pt/Dox in pH 5.5 phosphate buffered solution (PBS). Confocal imaging verifies that PEG@Pt/Dox can efficiently enter Dox-resistant breast cancer cells (MCF-7/ADR), deliver Dox into the cytoplasm when incubated for 1 h or 12 h, and release Dox into the nucleus when incubation is prolonged to 24 h. Cell transmission electron microscopy and flow cytometry also confirm that PEG@Pt/Dox could be internalized by cells. Upon irradiation by an 808 nm laser, the anticancer effect of PEG@Pt/Dox is significantly improved and kills approximately 84% of cancer cells when the concentration of Dox is 8 μg/mL. The killing efficacy of MCF-7/ADR cells is significantly higher in the combination group than in the monochemotherapy group. Hence, multifunctional nanoplatform PEG@Pt/Dox presents an effective strategy to realize efficient combination of chemotherapy and photothermals for drug-resistant cancer.

摘要

高效的癌症治疗仍然是目前的主要挑战。在这项研究中,我们开发了一种介孔铂纳米粒子(mesoPt)为基础的纳米平台,用于有效的肿瘤治疗,整合计算机断层扫描(CT)成像、光热转换和化疗药物输送能力。介孔铂纳米粒子是通过使用 Pluronic F127 作为结构导向剂来简便合成的,不需要种子或有机试剂,具有球形结构和均匀的直径为 94nm。mesoPt 的表面用聚乙二醇(PEG)进行修饰,所制备的 mesoPt-PEG 具有优异的生物相容性。通过静电吸附进一步制备载多柔比星(Dox)的 PEG@Pt(PEG@Pt/Dox),载药量高达 25%。体外研究表明,Dox 可以在 pH 5.5 的磷酸盐缓冲溶液(PBS)中从 PEG@Pt/Dox 中可控释放。共聚焦成像验证了 PEG@Pt/Dox 可以有效地进入多柔比星耐药乳腺癌细胞(MCF-7/ADR),孵育 1 小时或 12 小时后将 Dox 输送到细胞质中,孵育时间延长至 24 小时后将 Dox 释放到细胞核中。细胞透射电子显微镜和流式细胞术也证实了 PEG@Pt/Dox 可以被细胞内化。当用 808nm 激光照射时,PEG@Pt/Dox 的抗癌效果显著提高,当 Dox 的浓度为 8μg/mL 时,大约 84%的癌细胞被杀死。在联合组中,MCF-7/ADR 细胞的杀伤效果明显高于单化疗组。因此,多功能纳米平台 PEG@Pt/Dox 为实现耐药性癌症的化疗和光热的高效结合提供了一种有效的策略。

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