王婉玉, 程永忠, 高祥. 纳米递送系统增效PROTAC乳腺癌治疗的研究进展J. 药学学报, 2025, 60(11): 3297-3308. DOI: 10.16438/j.0513-4870.2025-0366
引用本文: 王婉玉, 程永忠, 高祥. 纳米递送系统增效PROTAC乳腺癌治疗的研究进展J. 药学学报, 2025, 60(11): 3297-3308. DOI: 10.16438/j.0513-4870.2025-0366
WANG Wan-yu, CHENG Yong-zhong, GAO Xiang. Advances in nanoparticle delivery systems for enhanced PROTAC therapy of breast cancerJ. Acta Pharmaceutica Sinica, 2025, 60(11): 3297-3308. DOI: 10.16438/j.0513-4870.2025-0366
Citation: WANG Wan-yu, CHENG Yong-zhong, GAO Xiang. Advances in nanoparticle delivery systems for enhanced PROTAC therapy of breast cancerJ. Acta Pharmaceutica Sinica, 2025, 60(11): 3297-3308. DOI: 10.16438/j.0513-4870.2025-0366

纳米递送系统增效PROTAC乳腺癌治疗的研究进展

Advances in nanoparticle delivery systems for enhanced PROTAC therapy of breast cancer

  • 摘要: 乳腺癌是全球常见恶性肿瘤之一, 2022年新发患者数高达230万例, 死亡人数约67万例。目前, 乳腺癌相关蛋白因缺乏活性位点难以被传统小分子抑制剂靶向, 同时药物治疗存在获得性耐药率高等问题, 严重影响临床疗效。蛋白降解靶向嵌合体(proteolysis-targeting chimera, PROTAC) 技术的出现为上述困境提供了解决方案。然而, 要实现临床转化PROTAC需要解决水溶性差、生物利用度低及靶向性不足等问题, 而多功能纳米递送系统可为其提供技术支持。本文综述了PROTAC纳米技术在乳腺癌治疗中的最新进展, 重点关注纳米递送平台设计策略及抗肿瘤联合增效机制, 并对该技术面临的挑战及未来发展方向进行了探讨。利用纳米技术递送PROTAC, 不仅能突破传统疗法的局限, 还为乳腺癌精准治疗提供了新思路。

     

    Abstract: Breast cancer remains one of the most prevalent malignancies worldwide, with approximately 2.3 million new cases and 670 000 deaths reported globally in 2022. Current therapeutic challenges include the difficulty in targeting breast cancer-associated proteins lacking active sites through traditional small-molecule inhibitors, as well as the high incidence of acquired drug resistance, which collectively undermine treatment outcomes. The advent of proteolysis-targeting chimera (PROTAC) technology has provided a solution, offering a unique protein degradation mechanism to circumvent these limitations. Nevertheless, clinical translation of PROTACs requires addressing inherent limitations such as poor solubility, low bioavailability, and insufficient targeting specificity. To overcome these barriers, multifunctional nano-delivery systems have emerged as a promising technological platform to enhance the therapeutic potential of PROTACs. This review systematically examines the latest advances in nanotechnology-enabled PROTAC delivery for breast cancer treatment, with particular emphasizes rational nanocarrier design principles and synergistic mechanisms of antitumor combination therapies. We further critically analyze persistent translational challenges and propose forward-looking solutions. The integration of nanotechnology with PROTACs not only overcomes the limitations of traditional therapies but also offers new insights into the precise treatment of breast cancer.

     

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