Zwitterionic daptomycin mineralized gold nanoflowers based nanodrugs for enhanced anti-glioma therapy

Traditional drugs face challenges due to low targeting efficiency and glioblastoma (GBM) cell resistance. Effective drug delivery is crucial to reduce the risk of postoperative recurrence in patients with glioma. A stable and multifunctional targeted nanodrug combining photothermal therapy and chemotherapy can be an effective approach to improve treatment outcomes. Herein, thiolated doxorubicin (SH-DOX), zwitterionic thiolated sulfobetaine (SB-SH), and targeting ligands c(RGDfC) were modified on the surfaces of zwitterionic daptomycin-mineralized gold nanoflowers (Au NFs) via Au–S bonds, and temozolomide (TMZ) was physically adsorbed onto the surfaces of daptomycin-mineralized Au NFs to prepare a multifunctional targeted nanodrug (SBDTC@Au NFs). SBDTC@Au NFs exhibit a flower-like morphology, with average particle size of 56.5 nm as shown in TEM images. These nanodrugs demonstrate high drug release in the weakly acidic tumor microenvironment and show good stability in complex media due to the presence of zwitterionic molecules on their surface. The drug showed an inhibition rate of 79.7 % against HS683 glioma cells, outperforming free DOX and TMZ. Cell uptake experiments confirmed that c(RGDfC) modification significantly enhanced targeting efficiency. In vivo experiments revealed that, after 14 days of treatment, the tumor inhibition rate in the SBDTC@Au NFs photothermal group reached 91.6 %. This study provides an innovative strategy for brain glioma treatment through multifunctional synergy and lays the foundation for the development of efficient and stable anti-tumor nanomedicines.