β-cyclodextrin(βCD)-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, a well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)₁₄) was synthesized via a couple reaction between βCD-based 14 arms poly(ε-caprolactone) (βCD-(PCL)₁₄) and disulfide-containing α-alkyne dextran (alkyne-SS-Dex), and acted as theranostic nanoparticles for tumor-targeted MRI and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX), and superparamagnetic iron oxide (SPIO) particles were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)₁₄@DOX-SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to the folate receptor-mediated endocytosis process of the nanoparticles and glutathione (GSH), which triggered disulfide-bonds cleaving. Moreover, (FA-Dex-SS)-βCD-(PCL)₁₄@DOX-SPIO showed strong MRI contrast enhancement properties. In conclusion, folic acid-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.

We designed a nanoplatform TMPD coated with metal-phenolic networks for the co-delivery of Mn ²⁺ and DOX with the aim to amplify the STING signal and potentiate cancer therapy. This nanoplatform induced a robust innate and adaptive immunity response.

Melanoma is highly dependent on cellular metabolism, but current treatments show limited effectiveness. Despite the promising antitumor properties of curcumin, its clinical utility is limited by its poor bioavailability and potential systemic toxicity. To address these challenges, we formulated curcumin-loaded polyethylene glycol-polycaprolactone (PEG-PCL) nanoparticles, denoted as PEG-PCL@Cur. We employed omics technologies to investigate their impact on melanoma at the molecular level. In vitro studies revealed that PEG-PCL@Cur notably suppressed the growth, movement, and invasiveness of A375 melanoma cells in a dose-dependent manner. Untargeted metabolomics identified 347 metabolites that were significantly altered. A decrease in fumaric acid levels indicated the suppression of oxidative phosphorylation and a shift in metabolism. Proteomics further confirmed the downregulation of key mitochondrial proteins, such as SDHA, pointing to mitochondrial dysfunction. Mechanistically, PEG-PCL@Cur increased reactive oxygen species (ROS) production by raising NADH levels and inhibiting SDHA expression. This led to a reduction in the level of fumaric acid production and a disruption of the tricarboxylic acid (TCA) cycle. Additionally, PEG-PCL@Cur hindered the generation of inorganic phosphate (Pi), resulting in a decreased level of ATP production. These metabolic changes promoted apoptosis and enhanced melanoma cell death. In vivo, PEG-PCL@Cur significantly curtailed tumor growth in a melanoma xenograft model and displayed an enhanced biocompatibility. Histological analysis showed extensive tumor necrosis, diminished proliferation markers, and elevated levels of apoptosis indicators. Overall, our integrated metabolomic and proteomic approach highlights how PEG-PCL@Cur targets SDHA-mediated metabolic reprogramming and mitochondrial dysfunction. This discovery positions PEG-PCL@Cur as a promising nanoplatform for melanoma therapy and offers valuable insights into the development of targeted nanomedicines.