Shi Yongli, Zhu Huiqing, Xu Suyue, Zhao Jingya, Wang Yuxin, Pan Xiaofei, Zhao Bingqian, Sun Zeyu, Yin Yili, Xu Linyin, Wei Fengjiao, He Sisi, Hou Xueyan, Xue Jintao
College of pharmacy, Xinxiang Medical University, dec00c, Xinxiang, PR China.
College of pharmacy, Xinxiang Medical University, dec00c, Xinxiang, PR China.
Colloids Surf B Biointerfaces. 2025 Mar;247:114433. doi: 10.1016/j.colsurfb.2024.114433. Epub 2024 Dec 4.
Therapy and metastasis pose significant challenges for breast cancer therapy. Locoregional chemotherapy presents a promising strategy to address these dilemmas. In this study, a doxorubicin-loaded injectable hydrogel based on hyaluronic acid (DOX-MCHA) was fabricated for locoregional chemotherapy and inhibiting the metastasis of breast cancer. The high bio-safety of cargo-free hydrogels (MCHA) would enhance patient compliance. The sustained DOX release behaviors from DOX-MCHA (over 10 days) could reduce dosing frequency and achieve long-term therapeutic effects. The potent in vivo anti-tumor activity of DOX-MCHA was verified by the smallest tumor volumes, the largest number of apoptotic cells, and the strongest fluorescence intensity in TUNEL sections. Notably, the injectable DOX-MCHA not only greatly suppressed the growth of 4T1 tumor tissues, but also effectively curbed the liver and lung metastasis in vivo. Moreover, the survival of 4T1-tumor bearing mice was extended without obvious systemic toxicity. In brief, the novel injectable hydrogel developed in this study offers a new strategy for locoregional therapy and inhibiting metastasis of breast cancer.
治疗和转移给乳腺癌治疗带来了重大挑战。局部区域化疗是解决这些难题的一种有前景的策略。在本研究中，制备了一种基于透明质酸的载阿霉素可注射水凝胶（DOX-MCHA）用于局部区域化疗并抑制乳腺癌转移。无载药水凝胶（MCHA）的高生物安全性将提高患者的依从性。DOX-MCHA的阿霉素持续释放行为（超过10天）可降低给药频率并实现长期治疗效果。通过最小的肿瘤体积、最多的凋亡细胞数量以及TUNEL切片中最强的荧光强度，验证了DOX-MCHA在体内的强大抗肿瘤活性。值得注意的是，可注射的DOX-MCHA不仅极大地抑制了4T1肿瘤组织的生长，还在体内有效抑制了肝肺转移。此外，延长了荷4T1肿瘤小鼠的生存期，且无明显的全身毒性。简而言之，本研究中开发的新型可注射水凝胶为乳腺癌的局部区域治疗和抑制转移提供了一种新策略。
