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基于光敏剂功能化双等离子体光热纳米制剂的低功率单激光激活协同癌症光疗。

Low Power Single Laser Activated Synergistic Cancer Phototherapy Using Photosensitizer Functionalized Dual Plasmonic Photothermal Nanoagents.

机构信息

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering , Nanjing University , Nanjing 210023 , China.

Department of Physical Chemistry, School of Science , China Pharmaceutical University , Nanjing 210009 , China.

出版信息

ACS Nano. 2019 Feb 26;13(2):2544-2557. doi: 10.1021/acsnano.8b09552. Epub 2019 Feb 11.


DOI:10.1021/acsnano.8b09552
PMID:30730695
Abstract

Combination therapy, especially photodynamic/photothermal therapy (PDT/PTT), has shown promising applications in cancer therapy. However, sequential irradiation by two different laser sources and even the utilization of single high-power laser to induce either combined PDT/PTT or individual PTT will be subjected to prolonged treatment time, complicated treatment process, and potential skin burns. Thus, low power single laser activatable combined PDT/PTT is still a formidable challenge. Herein, we propose an effective strategy to achieve synergistic cancer phototherapy under low power single laser irradiation for short duration. By taking advantage of dual plasmonic PTT nanoagents (AuNRs/MoS), a significant increase in temperature up to 60 °C with an overall photothermal conversion efficiency (PCE) of 68.8% was achieved within 5 min under very low power (0.2 W/cm) NIR laser irradiation. The enhanced PCE and PTT performance is attributed to the synergistic plasmonic PTT effect (PPTT) of dual plasmonic nanoagents, promoting simultaneous release (85%) of electrostatically bonded indocyanine green (ICG) to induce PDT effects, offering simultaneous PDT/synergistic PPTT. Both in vitro and in vivo investigations reveal complete cell/tumor eradication, implying that simultaneous PDT/synergistic PPTT effects induced by AuNRs/MoS-ICG are much superior over individual PDT or synergistic PPTT. Notably, synergistic PPTT induced by dual plasmonic nanoagents also demonstrates higher in vivo antitumor efficacy than either individual PDT or PTT agents. Taken together, under single laser activation with low power density, the proposed strategy of simultaneous PDT/synergistic PPTT effectively reduces the treatment time, achieves high therapeutic index, and offers safe treatment option, which may serve as a platform to develop safer and clinically translatable approaches for accelerating cancer therapeutics.

摘要

联合治疗,特别是光动力/光热治疗(PDT/PTT),在癌症治疗中显示出了有前途的应用。然而,两种不同激光源的顺序照射,甚至利用单束高功率激光来诱导联合 PDT/PTT 或单独 PTT,都将导致治疗时间延长、治疗过程复杂和潜在的皮肤灼伤。因此,低功率单激光激活的联合 PDT/PTT 仍然是一个巨大的挑战。在此,我们提出了一种在低功率单激光照射下实现协同癌症光疗的有效策略,治疗时间短。利用双等离子体 PTT 纳米剂(AuNRs/MoS),在非常低的功率(0.2 W/cm)近红外激光照射下,5 分钟内温度可显著升高至 60°C,整体光热转换效率(PCE)达到 68.8%。增强的 PCE 和 PTT 性能归因于双等离子体纳米剂的协同等离子体 PTT 效应(PPTT),促进静电键合的吲哚菁绿(ICG)的同时释放(85%),从而诱导 PDT 效应,提供同时的 PDT/协同 PPTT。体外和体内研究均显示完全细胞/肿瘤清除,表明由 AuNRs/MoS-ICG 诱导的同时 PDT/协同 PPTT 效应明显优于单独的 PDT 或协同 PPTT。值得注意的是,双等离子体纳米剂诱导的协同 PPTT 也比单独的 PDT 或 PTT 剂具有更高的体内抗肿瘤疗效。综上所述,在低功率密度的单激光激活下,同时进行 PDT/协同 PPTT 的策略有效地减少了治疗时间,实现了高治疗指数,并提供了安全的治疗选择,这可能为开发更安全、更具临床转化性的方法以加速癌症治疗提供了一个平台。

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