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负载锌离子配位光敏剂的前列腺癌靶向脂质体用于增强化学-光动力疗法

Prostate Cancer-Targeting Liposome Loaded with Zinc Ion-Coordinated Photosensitizer for Enhanced Chemo-Photodynamic Therapy.

作者信息

Gao Li, Tang Zhisheng, Xiao Dongming, Chen Xu, Zhu Yizhun

机构信息

State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau 999078, China.

College of Pharmacy, Guilin Medical University, Guilin 541004, China.

出版信息

Pharmaceutics. 2025 Mar 31;17(4):448. doi: 10.3390/pharmaceutics17040448.

Abstract

Prostate cancer (PCa) is the second most prevalent cancer in males globally, impacting one out of every six males. However, the therapeutic effect of chemotherapy on PCa is restricted. To address this, we developed a tumor-targeted multifunctional liposomal platform (PTX-PS/Zn@Lip-Apt) for zinc-enhanced chemo-photodynamic therapy of PCa. Co-delivery of PTX and an aggregation-induced emission photosensitizer (TPEDPD) enables combined chemotherapy and photody-namic therapy. Zinc ions were loaded into liposomes to improve the chemosensitivity of PCa to chemodrugs. Then, the AS1411 aptamer was further modified onto the sur-face of the liposome to enhance its tumor targeting ability. Moreover, to improve the cellular uptake efficiency of the nanoparticles, the photochemical internalization (PCI) strategy was also employed. : In vitro experiments indicated that aptamer conjugation and PCI application enhanced the cellular uptake and cytotoxicity of PTX/PS-Zn@Lip-Apt. The zinc ion enhanced cytotoxicity could also be found. In vivo experiments demonstrated the good antitumor effect and biosafety of PTX/PS-Zn@Lip-Apt. : Our findings provide an important basis for innovatively applying zinc-enhanced combined chemo-photodynamic therapy in prostate cancer.

摘要

前列腺癌(PCa)是全球男性中第二常见的癌症,每六名男性中就有一人受其影响。然而,化疗对PCa的治疗效果有限。为了解决这一问题,我们开发了一种肿瘤靶向多功能脂质体平台(PTX-PS/Zn@Lip-Apt),用于前列腺癌的锌增强化学-光动力治疗。同时递送紫杉醇(PTX)和一种聚集诱导发光光敏剂(TPEDPD)可实现联合化疗和光动力治疗。将锌离子载入脂质体以提高PCa对化疗药物的化学敏感性。然后,将AS1411适配体进一步修饰到脂质体表面以增强其肿瘤靶向能力。此外,为了提高纳米颗粒的细胞摄取效率,还采用了光化学内化(PCI)策略。体外实验表明,适配体偶联和PCI应用增强了PTX/PS-Zn@Lip-Apt的细胞摄取和细胞毒性。还发现了锌离子增强的细胞毒性。体内实验证明了PTX/PS-Zn@Lip-Apt具有良好的抗肿瘤效果和生物安全性。我们的研究结果为创新性地将锌增强联合化学-光动力疗法应用于前列腺癌提供了重要依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8d7/12030104/e8d18ed20c5a/pharmaceutics-17-00448-g001.jpg

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