College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
Guang an'men Hospital China Academy of Chinese Medical Sciences, Beijing 100053, China.
Eur J Pharm Biopharm. 2021 Sep;166:30-43. doi: 10.1016/j.ejpb.2021.05.029. Epub 2021 Jun 8.
Breast cancer, as a malignant disease that seriously threatens women's health, urgently needs to be researched to develop effective and safe therapeutic drugs. Nanoparticle drug delivery systems (NDDS), provide a powerful means for drug targeting to the breast cancer, enhancing the bioavailability and reducing the adverse effects of anticancer drug. However, the breast cancer microenvironment together with heterogeneity of cancer, impedes the tumor targeting effect of NDDS. Breast cancer microenvironment, exerts endogenous stimuli, such as hypoxia, acidosis, and aberrant protease expression, shape a natural shelter for tumor growth, invasion and migration. On the basis of the ubiquitous of endogenous stimuli in the breast cancer microenvironment, researchers exploited them to design the stimuli-responsive NDDS, which response to endogenous stimulus, targeted release drug in breast cancer microenvironment. In this review, we highlighted the effect of the breast cancer microenvironment, summarized innovative NDDS responsive to the internal stimuli in the tumor microenvironment, including the material, the targeting groups, the loading drugs, targeting position and the function of stimuli-responsive nanoparticle drug delivery system. The limitations and potential applications of the stimuli-responsive nanoparticle drug delivery systems for breast cancer treatment were discussed to further the application.
乳腺癌作为一种严重威胁女性健康的恶性疾病,迫切需要研究开发有效且安全的治疗药物。纳米药物递送系统(NDDS)为药物靶向乳腺癌提供了有力手段,提高了抗癌药物的生物利用度,降低了其不良反应。然而,乳腺癌微环境与肿瘤的异质性一起,阻碍了 NDDS 的肿瘤靶向效果。乳腺癌微环境会产生内源性刺激,如缺氧、酸中毒和异常蛋白酶表达,为肿瘤生长、侵袭和迁移形成天然庇护所。基于乳腺癌微环境中内源性刺激的普遍存在,研究人员利用这些刺激来设计对内源性刺激做出响应的刺激响应型 NDDS,使其在乳腺癌微环境中靶向释放药物。在本综述中,我们强调了乳腺癌微环境的作用,总结了创新性的 NDDS 对肿瘤微环境中内源性刺激的响应,包括材料、靶向基团、负载药物、靶向位置和刺激响应型纳米药物递送系统的功能。讨论了刺激响应型纳米药物递送系统用于乳腺癌治疗的局限性和潜在应用,以进一步推动其应用。