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具有疏水性紫杉醇的多功能介孔聚多巴胺用于光声成像引导的化疗-光热协同治疗。

Multifunctional Mesoporous Polydopamine With Hydrophobic Paclitaxel For Photoacoustic Imaging-Guided Chemo-Photothermal Synergistic Therapy.

机构信息

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, People's Republic of China.

出版信息

Int J Nanomedicine. 2019 Nov 4;14:8647-8663. doi: 10.2147/IJN.S218632. eCollection 2019.

Abstract

BACKGROUND

Chemo-photothermal therapy has attracted intensive attention because of its low side effects and better therapeutic efficiency. Although many photothermal agents have been loaded with chemotherapeutic drugs for chemo-photothermal therapy, their applications are limited by complex synthetic protocols and long-term safety. Therefore, there is significant clinical value in the development of a simple system of biocompatible and biodegradable photothermal nanomaterials with high payloads of chemotherapeutic drugs for chemo-photothermal synergistic therapy.

MATERIALS AND METHODS

In this study, PEG-modified polydopamine nanoparticles with mesoporous structure (MPDA-PEG) were successfully obtained by an emulsion-induced interface assembly strategy. Subsequently, paclitaxel (PTX) dissolved in acetone was loaded into the mesoporous channels of MPDA-PEG nanoparticles by solution absorption method. A PTX-loaded MPDA-PEG (MPDA-PEG-PTX) nanoplatform for combination of photothermal therapy (PTT) and chemotherapy was developed.

RESULTS

The synthesized MPDA-PEG nanoparticles had a great photothermal effect under near-infrared (NIR) laser irradiation and exhibited an enhanced photothermal effect with the increase of particle size. Meanwhile, MPDA-PEG nanoparticles also had a high payload of PTX, and the PTX release could be greatly accelerated by elevated temperature from photothermal effect. In MTT cytotoxicity assay, A549 cells incubated with MPDA-PEG-PTX under NIR laser irradiation (PTT + chemotherapy group) exhibited better therapeutic effect than single chemotherapy (MPDA-PEG-PTX group) and PTT (MPDA-PEG + Laser group). The synergistic therapeutic effect of MPDA-PEG-PTX with NIR laser irradiation in vivo was further investigated under the guidance of photoacoustic imaging (PAI), tumors of nude mice treated with MPDA-PEG-PTX with NIR laser irradiation were completely eliminated with minimal side effect.

CONCLUSION

The MPDA-PEG-PTX nanoplatform is a simple and effective platform which can completely inhibit tumor growth with minimal side effects under NIR irradiation, and it exhibits better therapeutic effect than single chemotherapy and PTT.

摘要

背景

化学-光热疗法因其副作用低、治疗效率高而受到广泛关注。虽然许多光热剂已经负载了化疗药物用于化学-光热治疗,但由于复杂的合成方案和长期安全性,它们的应用受到限制。因此,开发一种简单的生物相容性和可生物降解的光热纳米材料系统,具有高载药量的化疗药物,用于化学-光热协同治疗,具有重要的临床价值。

材料与方法

本研究采用乳液诱导界面组装策略成功获得了具有介孔结构的聚多巴胺纳米粒子(MPDA-PEG)。随后,通过溶液吸收法将溶解在丙酮中的紫杉醇(PTX)载入 MPDA-PEG 纳米粒子的介孔通道中。开发了一种用于光热治疗(PTT)和化学疗法联合治疗的载紫杉醇的 MPDA-PEG(MPDA-PEG-PTX)纳米平台。

结果

合成的 MPDA-PEG 纳米粒子在近红外(NIR)激光照射下具有很好的光热效应,并且随着粒径的增加,其光热效应增强。同时,MPDA-PEG 纳米粒子还具有高载药量的 PTX,并且光热效应引起的温度升高可以大大加速 PTX 的释放。在 MTT 细胞毒性实验中,与 NIR 激光照射下孵育的 MPDA-PEG-PTX(PTT+化疗组)相比,单独化疗(MPDA-PEG-PTX 组)和 PTT(MPDA-PEG+激光组)对 A549 细胞的治疗效果更好。在光声成像(PAI)的指导下,进一步研究了体内 NIR 激光照射下 MPDA-PEG-PTX 的协同治疗效果,经 NIR 激光照射处理的裸鼠肿瘤完全消除,副作用最小。

结论

在 NIR 照射下,MPDA-PEG-PTX 纳米平台是一种简单有效的平台,可在最小副作用下完全抑制肿瘤生长,其治疗效果优于单独化疗和 PTT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c5/6839591/be8fd69b72c4/IJN-14-8647-g0001.jpg

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