Novel Donor-Acceptor Conjugated Polymer-Based Nanomicelles for Photothermal Therapy in the NIR Window.
Novel Donor-Acceptor Conjugated Polymer-Based Nanomicelles for Photothermal Therapy in the NIR Window.
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DOI：
10.1021/acs.biomac.2c00330
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发表时间：
2022-07
影响因子：
6.2
通讯作者：
Hanning Zhang;Shuangyu Tian;Mu Li;Jinhai Xie;Honglian Dai;Liuyong Hu;Lesan Yan
中科院分区：
文献类型：
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作者：
Hanning Zhang;Shuangyu Tian;Mu Li;Jinhai Xie;Honglian Dai;Liuyong Hu;Lesan Yan
以2，6-二（三甲基锡）-N-二噻吩并[3，2-B：20，30-d]吡咯为给电子单元，3，6-二（5-溴噻吩-2-基）-2，5-双十六烷基吡咯并[3，4-c]吡咯-1，4-二酮为受电子单元，通过D-A聚合，设计并合成了一种新型的给-受体共轭聚合物PDPPDTP。所制备的聚合物在700-900 nm的近红外（NIR）范围内具有强吸收。在808 nm的光照射下，该材料具有良好的光热性能。其次，利用微乳液法，将可生物降解的两亲性聚合物聚乙二醇-聚己内酯包覆到新型共轭聚合物纳米胶束中。通过透射电子显微镜和动态光散射表征，得到的PDP-PDTP胶束为规则的球形结构，流体动力学直径约为78 nm。值得注意的是，胶束表现出良好的稳定性，并且胶束中的共轭聚合物的包封率为约80%。体外细胞实验表明，该纳米胶束不仅具有良好的生物相容性和低毒性，而且在808 nm的近红外光照射下，能有效抑制乳腺癌细胞4 T1的增殖。此外，光热疗法（PTT）的体内研究表明，PDP-PDTP-负载胶束在小鼠肿瘤模型中表现出显著的肿瘤生长抑制作用，表明负载这种新型共轭聚合物的纳米胶束可以作为一种新型的治疗诊断剂进一步开发并应用于肿瘤的PTT。
In this study, a novel donor-acceptor conjugated polymer PDPPDTP was designed and synthesized by D-A polymerization using 2,6-di(trimethyltin)-N-dithieno[3,2-b:20,30-d]pyrrole as the electron-donating (D) unit and 3,6-bis(5-bromothiophen-2-yl)-2,5-dihexadecylpyrrolo[3,4-c]pyrrole-1,4-dione as the electron-accepting (A) unit. The prepared polymer has strong absorption in the near-infrared (NIR) range of 700-900 nm. Moreover, it shows excellent photothermal performance under irradiation at 808 nm. Next, the biodegradable amphiphilic polymer polyethylene glycol-polycaprolactone was used to encapsulate the new conjugated polymer into nanomicelles by the microemulsion method. The obtained PDPPDTP-loaded micelles exhibited a regular spherical structure, and their hydrodynamic diameter was about 78 nm, characterized by transmission electron microscopy and dynamic light scattering. Notably, the micelles exhibited good stability, and the encapsulation efficiency of the conjugated polymer in the micelles was ∼80%. In vitro cell experiments demonstrated that the nanomicelles not only showed good biocompatibility and low toxicity but also could effectively inhibit the proliferation of breast cancer cells 4T1 under the NIR light irradiation of 808 nm. Furthermore, in vivo studies of photothermal therapy (PTT) efficacy showed that the PDPPDTP-loaded micelles exhibited a remarkable tumor growth inhibition in a syngeneic murine tumor model, indicating that the nanomicelles loaded with this novel conjugated polymer could be further explored as a new type of theranostic agent and applied in the PTT of tumors.