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使用光/热响应纳米平台共递送喜树碱(CPT)和紫杉醇(PTX)前药用于三阴性乳腺癌治疗。

Co-delivery CPT and PTX prodrug with a photo/thermo-responsive nanoplatform for triple-negative breast cancer therapy.

作者信息

Zhou Wenhui, Ma Xiaodong, Wang Jie, Xu Xiaoyu, Koivisto Oliver, Feng Jing, Viitala Tapani, Zhang Hongbo

机构信息

Pharmaceutical Sciences Laboratory Åbo Akademi University Turku Finland.

Turku Bioscience Centre University of Turku and Åbo Akademi University Turku Finland.

出版信息

Smart Med. 2022 Dec 27;1(1):e20220036. doi: 10.1002/SMMD.20220036. eCollection 2022 Dec.

Abstract

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.

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方面具有巨大潜力;然而,游离化疗给药的脱靶效应和副作用仍然是一个重大挑战。在本研究中,我们开发了一种光/热响应纳米平台,可通过光热疗法与多药疗法联合用于TNBC治疗。通过将化疗药物PTX前药偶联在介孔二氧化硅包覆的金纳米棒纳米颗粒表面,然后负载另一种化疗药物CPT,Au@MSN-PTX@CPT纳米颗粒表现出良好的光热响应、氧化还原响应药物释放和癌细胞抑制能力。此外,我们用温度敏感聚合物聚(N-异丙基丙烯酰胺-co-甲基丙烯酸)(p(NIPAM-co-MAAc))进一步包覆Au@MSN-PTX@CPT纳米颗粒,聚合物包覆的Au@MSN-PTX@TPT@聚合物纳米颗粒表现出完美的近红外(NIR)光控药物释放。最后,将Au@MSN-PTX@CPT@聚合物纳米颗粒注射到4T1乳腺癌小鼠模型中。Au@MSN-PTX@CPT@聚合物纳米颗粒优先在肿瘤部位蓄积,与650 nm激光治疗联合使用时,化疗损伤减轻,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良好的化疗药物控释方法,为TNBC联合治疗提供了一个很好的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab34/11235718/5fb6de248693/SMMD-1-e20220036-g002.jpg

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