具有光/热响应纳米平台的共递送CPT和PTX前药用于三阴性乳腺癌症治疗

Smart medicine Pub Date : 2022-12-27 eCollection Date: 2022-12-01 DOI:10.1002/SMMD.20220036
Wenhui Zhou, Xiaodong Ma, Jie Wang, Xiaoyu Xu, Oliver Koivisto, Jing Feng, Tapani Viitala, Hongbo Zhang
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摘要

三阴性乳腺癌(TNBC)仍然是女性中最具侵袭性的癌症。联合化疗在癌症治疗中具有巨大潜力;然而,游离化疗的脱靶和副作用仍然是一大挑战。在这项研究中,我们开发了一种光/热响应纳米平台,可通过光热疗法结合多药疗法用于 TNBC 的治疗。通过在介孔二氧化硅包覆的金纳米棒纳米颗粒表面共轭化疗药物PTX原药,再负载另一种化疗药物CPT,Au@MSN-PTX@CPT纳米颗粒表现出很好的光热响应、氧化还原反应药物释放和癌细胞抑制能力。此外,我们还在 Au@MSN-PTX@CPT 纳米颗粒上包覆了对温度敏感的聚合物聚(N-异丙基丙烯酰胺-甲基丙烯酸)(p(NIPAM-co-MAAc)),包覆聚合物的 Au@MSN-PTX@TPT@ 聚合物纳米颗粒表现出完美的近红外光控释药能力。最后,将 Au@MSN-PTX@CPT@ 聚合物纳米粒子注射到 4T1 乳腺癌小鼠模型中。结果表明,Au@MSN-PTX@CPT@聚合物纳米粒子能在肿瘤部位聚集,与650 nm激光治疗相结合,能减少化疗损伤,具有很强的抗肿瘤活性。总之,我们开发的Au@MSN-PTX@CPT@聚合物纳米颗粒是一种很好的化学药物可控递送方法,为TNBC联合治疗提供了很好的选择。
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Co-delivery CPT and PTX prodrug with a photo/thermo-responsive nanoplatform for triple-negative breast cancer therapy.

Triple-negative breast cancer (TNBC) is still the most aggressive cancer in women. Combination chemotherapy holds great potential for cancer therapy; however, the off-target and side effects of free chemotherapy administration remain a major challenge. In this study, we developed a photo/thermo-responsive nanoplatform that can be used for TNBC treatment via photothermic therapy in combination with multidrug therapy. By conjugating the chemotherapy drug PTX prodrug on the surface of mesoporous silica-coated gold nanorod nanoparticles and then loading another chemotherapy drug, CPT, the Au@MSN-PTX@CPT nanoparticles exhibited great photothermal response, redox response drug release and cancer cell inhibition abilities. Otherwise, we further coated the Au@MSN-PTX@CPT nanoparticle with a temperature-sensitive polymer poly(N-isopropylacrylamide-co-methacrylic acid) (p(NIPAM-co-MAAc)), and the polymer-coated Au@MSN-PTX@TPT@polymer nanoparticles showed perfect near-infrared (NIR) light controlled drug release. Finally, the Au@MSN-PTX@CPT@polymer nanoparticles were injected into the 4T1 breast cancer mouse model. The Au@MSN-PTX@CPT@polymer nanoparticles preferably accumulated at the tumor site and had reduced chemotherapy injuries and great antitumor activity when combined with 650 nm laser treatment. In summary, our developed Au@MSN-PTX@CPT@polymer nanoparticles served as a good method for controlled chemodrug delivery and provided a good choice for TNBC combination therapy.

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