Yang Lei, Sun Qiang, Chen Shiyin, Ma Dongshen, Qi Yao, Liu Hongmei, Tan Sumin, Yue Qin, Cai Lulu
Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China; Department of Pharmacy, People's Hospital of Jianyang, Jianyang 641400, China.
Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China.
J Control Release. 2025 Jan 10;377:563-577. doi: 10.1016/j.jconrel.2024.11.055. Epub 2024 Nov 29.
Calcium (Ca) overload therapy gained significant attention in oncology. However, its therapeutic efficacy remained limited due to insufficient Ca accumulation at the tumor site and suboptimal intracellular Ca influx. In this study, gambogic acid (GA), a natural phenolic compound known to promote Ca influx, was encapsulated within an enzyme-triggered, pH-responsive hydrogel (GM@Lip@CHP-Gel) containing Ca hydrogen phosphate nanowires (CHP) to achieve a synergistic approach for bone tumor therapy. GM@Lip@CHP-Gel selectively responded to the slightly acidic tumor microenvironment, triggering degradation of its 3D network structure and sustaining the release of GA and Ca into tumor cells. GA subsequently stimulated Ca influx in tumor cells, effectively disrupting Ca homeostasis. CHP nanowires served as a continuous Ca source, enhancing GA-mediated Ca overload and promoting mitochondrial apoptosis in tumor cells. The combined strategy resulted in an in vivo tumor suppression rate of 79 % and a lung metastasis inhibition rate of 89.4 %, with a protective effect on bone tissue. The naturally derived, Ca-mediated treatment demonstrated physiochemical stability in physiological environments and minimized side effects on healthy organs, positioning it as a promising approach for clinical bone cancer therapy.
钙（Ca）超载疗法在肿瘤学领域引起了广泛关注。然而，由于肿瘤部位钙积累不足以及细胞内钙内流不理想，其治疗效果仍然有限。在本研究中，藤黄酸（GA）是一种已知可促进钙内流的天然酚类化合物，被包裹在一种含有磷酸氢钙纳米线（CHP）的酶触发、pH响应水凝胶（GM@Lip@CHP-Gel）中，以实现骨肿瘤治疗的协同方法。GM@Lip@CHP-Gel对微酸性肿瘤微环境具有选择性响应，触发其三维网络结构的降解，并持续将GA和Ca释放到肿瘤细胞中。GA随后刺激肿瘤细胞中的钙内流，有效破坏钙稳态。CHP纳米线作为持续的钙源，增强了GA介导的钙超载并促进肿瘤细胞中的线粒体凋亡。联合策略导致体内肿瘤抑制率为79%，肺转移抑制率为89.4%，并对骨组织具有保护作用。这种天然来源的、钙介导的治疗方法在生理环境中表现出物理化学稳定性，并将对健康器官的副作用降至最低，使其成为临床骨癌治疗的一种有前景的方法。
