Leng Yurong, Wu Yanmei, Xiao Wenjing, Su Xiaoquan, Liu Zhe
School of Stomatology, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.
Jiangxi Province Key Laboratory of Oral Biomedicine, Nanchang 330006, China.
ACS Omega. 2024 Nov 18;9(48):47428-47435. doi: 10.1021/acsomega.4c04502. eCollection 2024 Dec 3.
Nanomedicine provides promising new methodologies for the treatment of tumors but still faces several limitations, including poor colloidal stability, uncontrollable drug release, and insufficient drug targeting. Herein, hyaluronic acid (HA) was used to modify the surface of mesoporous silica nanoparticles (MSNs) via a dynamic-covalent linker, phenylborate ester (PBAE), termed MA. The HA modifier provided enhanced colloidal stability to the hybrid nanoparticles. As expected, MA exhibited an improved biocompatibility and high potential for biomedical applications. Moreover, MA with a negatively charged surface effectively adsorbed the drug Doxorubicin (DOX) inside the carriers, ensuring minimal drug leakage. In an acidic and reactive oxygen species (ROS)-containing condition mimicking the tumor microenvironment, MA@DOX (MAD) continuously released its payloads, likely due to the cleavage of the pH/ROS-sensitive PBAE. Compared with free DOX, MAD had 2.2 times higher accessibility to tumor cells than free DOX. The favorable stability and cancer-selective drug release make this nanoformulation a promising platform for potent cancer treatment.
纳米医学为肿瘤治疗提供了有前景的新方法，但仍面临一些局限性，包括胶体稳定性差、药物释放不可控以及药物靶向性不足。在此，透明质酸（HA）通过动态共价连接体硼酸苯酯（PBAE）用于修饰介孔二氧化硅纳米颗粒（MSNs）的表面，称为MA。HA修饰剂提高了杂化纳米颗粒的胶体稳定性。正如预期的那样，MA表现出改善的生物相容性和在生物医学应用中的高潜力。此外，表面带负电荷的MA有效地将药物阿霉素（DOX）吸附在载体内部，确保药物泄漏最小化。在模拟肿瘤微环境的酸性和含活性氧（ROS）的条件下，MA@DOX（MAD）持续释放其有效载荷，这可能是由于pH/ROS敏感的PBAE的裂解。与游离DOX相比，MAD对肿瘤细胞的可及性比游离DOX高2.2倍。良好的稳定性和癌症选择性药物释放使这种纳米制剂成为有效癌症治疗的有前景的平台。
