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基于氯 e6 修饰的聚多巴胺纳米球的光动力/光热双重模式治疗剂用于增强癌症治疗。

Chlorin e6 Conjugated Poly(dopamine) Nanospheres as PDT/PTT Dual-Modal Therapeutic Agents for Enhanced Cancer Therapy.

机构信息

†The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China.

‡The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China.

出版信息

ACS Appl Mater Interfaces. 2015 Apr 22;7(15):8176-87. doi: 10.1021/acsami.5b01027. Epub 2015 Apr 10.

DOI:10.1021/acsami.5b01027
PMID:25837008
Abstract

Photodynamic therapy (PDT), using a combination of chemical photosensitizers (PS) and light, has been successfully applied as a noninvasive therapeutic procedure to treat tumors by inducing apoptosis or necrosis of cancer cells. However, most current clinically used PS have suffered from the instability in physiological conditions which lead to low photodynamic therapy efficacy. Herein, a highly biocompatible poly(dopamine) (PDA) nanoparticle conjugated with Chlorin e6 (referenced as the PDA-Ce6 nanosphere) was designed as a nanotherapeutic agent to achieve simultaneous photodynamic/photothermal therapy (PDT/PTT). Compared to the free Ce6, the PDA-Ce6 nanosphere exhibited significantly higher PDT efficacy against tumor cells, because of the enhanced cellular uptake and subsequently greater reactive oxygen species (ROS) production upon laser irradiation at 670 nm. Meanwhile, the PDA-Ce6 nanosphere could be also used as a photoabsorbing agent for PTT, because of the excellent photothermal conversion ability of PDA nanoparticle under laser irradiation at 808 nm. Moreover, our prepared nanosphere had extremely low dark toxicity, while excellent phototoxicity under the combination laser irradiation of 670 and 808 nm, both in vitro and in vivo, compared to any single laser irradiation alone. Therefore, our prepared PDA-Ce6 nanosphere could be applied as a very promising dual-modal phototherapeutic agent for enhanced cancer therapy in future clinical applications.

摘要

光动力疗法(PDT)是一种将化学光敏剂(PS)与光结合使用的治疗方法,已成功应用于通过诱导癌细胞凋亡或坏死来治疗肿瘤的非侵入性治疗方法。然而,大多数目前临床使用的 PS 都存在生理条件下的不稳定性,导致光动力疗法的疗效较低。在此,设计了一种高度生物相容的聚多巴胺(PDA)纳米粒子与氯代叶绿素 e6(称为 PDA-Ce6 纳米球)结合,作为一种纳米治疗剂来实现光动力/光热治疗(PDT/PTT)的联合治疗。与游离的 Ce6 相比,PDA-Ce6 纳米球对肿瘤细胞具有显著更高的 PDT 疗效,因为在 670nm 激光照射下,细胞摄取增强,随后产生更多的活性氧(ROS)。同时,由于 PDA 纳米粒子在 808nm 激光照射下具有优异的光热转换能力,PDA-Ce6 纳米球也可用作 PTT 的光吸收剂。此外,与任何单一激光单独照射相比,我们制备的纳米球在体外和体内均具有极低的暗毒性,同时在 670nm 和 808nm 组合激光照射下具有优异的光毒性。因此,我们制备的 PDA-Ce6 纳米球可作为一种很有前途的双模式光热治疗剂,用于未来临床应用中增强癌症治疗效果。

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