Ling-zhijie Kong,1,* Dong Zhou,2,* Guoyan Mo,3,* Mingyue Shu,3 Wenyan Yu,1 Hao Cheng,1 Kaichun Li1 

1Department of Oncology, Shanghai Fourth People’s Hospital, Tongji University School of Medicine, Shanghai, 200434, People’s Republic of China; 2The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China; 3China Key Laboratory of TCM Resource and Prescription, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, 430065, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Kaichun Li, Email likaichun@tongji.edu.cn

Introduction: The therapeutic efficacy of nanomedicine in oncology is predicated on its capacity to enhance drug uptake by cells and control drug release. While targeted nanomedicines are highly regarded for their potential, they are not spared from issues of colloidal instability and uncontrolled drug release.
Methods: The hybrid system (Au@SiO2-HA-DOX) was designed to enhance colloidal stability and facilitate controlled drug delivery by coating gold nanorods with silica shells and hyaluronic acid (HA) for tumor targeting. The nanoparticles were characterized for morphology, size, zeta potential, and photothermal properties. The loading efficiency of doxorubicin (DOX) and its release behavior in response to pH, reactive oxygen species (ROS), and NIR stimulation were evaluated.
Results: Under NIR irradiation, the nanoparticles exhibited excellent photothermal stability and sustained temperature elevation. In vitro studies demonstrated that the nanoparticles possessed good biocompatibility (cell viability exceeding 90%) and colloidal stability (7 days). The loading efficiency of DOX was enhanced to 65.9%, with sustained release characteristics. Furthermore, Au@SiO2-HA-DOX exhibited selective targeting and stronger cytotoxicity towards cancer cells. The cellular uptake efficiency was 1.7 times higher than that of the Free DOX at 24 h, with an IC50 value of 1.36 μM, compared to 2.01 μM for Free DOX. In vivo experiments in a mouse breast cancer model revealed significant tumor growth inhibited with NIR-assisted therapy, while maintaining stable body weight and preserving good biocompatibility.
Conclusion: This nanohybrid system represents a promising strategy for improving the efficacy of chemotherapy and reducing toxicity in cancer treatment. It enhances drug enrichment and release in tumor tissues while minimizing the impact on normal tissues.

Keywords: gold nanorods, high colloidal stability, pH/ROS-responsive, tumor microenvironment, tumor-targeted therapy