Smart PdH@MnO₂ Yolk–Shell Nanostructures for Spatiotemporally Synchronous Targeted Hydrogen Delivery and Oxygen-Elevated Phototherapy of Melanoma

Abstract

Hydrogen therapy, an emerging therapeutic strategy, has recently attracted much attention in anticancer medicine. Evidence suggests that hydrogen (H2) can selectively reduce intratumoral overexpressed hydroxyl radicals (•OH) to break the redox homeostasis and thereby lead to redox stress and cell damage. However, the inability to achieve stable hydrogen storage and efficient hydrogen delivery hinders the development of hydrogen therapy. Furthermore, oxygen (O2) deficiency in the tumor microenvironment (TME) and the electron–hole separation inefficiency in photosensitizers have severely limited the efficacy of photodynamic therapy (PDT). Herein, a smart PdH@MnO2/Ce6@HA (PHMCH) yolk–shell nanoplatform is designed to surmount these challenges. PdH tetrahedrons combine stable hydrogen storage and high photothermal conversion efficiency of palladium (Pd) nanomaterials with near-infrared-controlled hydrogen release. Subsequently, the narrow bandgap semiconductor manganese dioxide (MnO2) and the photosensitizer chlorin e6 (Ce6) are introduced into the PHMCH nanoplatform. Upon irradiation, the staggered energy band edges in heterogeneous materials composed of MnO2 and Ce6 can efficiently facilitate electron–hole separation for increasing singlet oxygen (1O2). Moreover, MnO2 nanoshells generate O2 in TME for ameliorating hypoxia and further improving O2-dependent PDT. Finally, the hyaluronic acid-modified PHMCH nanoplatform shows negligible cytotoxicity and selectively targets CD44-overexpressing melanoma cells. The synergistic antitumor performance of the H2-mediated gas therapy combined with photothermal and enhanced PDT can explore more possibilities for the design of gas-mediated cancer therapy.

Synergistic Reinforcing of Immunogenic Cell Death and Transforming Tumor‐Associated Macrophages Via a Multifunctional Cascade Bioreactor for Optimizing Cancer Immunotherapy

“…Finally, an appropriate amount of HA was added to get a HA layer, the resultant CCMH were gained and collected. [ 20 ] Meanwhile, as shown in Figure S1 (Supporting Information), color changes could be observed in the synthesis procedure of the CCMH. The lattice spacing of CuS@BSA observed using high‐resolution transmission electron microscopy (HRTEM) corresponds to the (102) plane according to the lattice parameters of CuS (JCPDS No.…”

“…[ 25 ] The high‐resolution O 1s XPS spectra of CaO 2 NPs revealed two peaks at ≈532.0 and 531.3 eV, which represents O − of CaO 2 NPs (Figure 1m). [ 20b ] For powder X‐ray diffraction (XRD) analysis, no distinct peaks were observed in the XRD pattern of CuS@MnO 2 . Therefore, the peaks and intensities of CCMH matched well with those of CaO 2 NPs (Figure S8, Supporting Information).…”

“…The CD44 receptor is typically highly expressed on the surface of various tumor cells (e.g., mouse breast cancer cells (4T1) and mouse colon cancer cells (CT26)); [ 20b,10a ] however, it is barely expressed in a normal cell line (e.g., human umbilical vein endothelial cells (HUVECs)). [ 29 ] HA conjugated NPs can preferentially target the CD44 receptor over‐expressed cells.…”

A NIR-II light-modulated injectable self-healing hydrogel for synergistic photothermal/chemodynamic/chemo-therapy of melanoma and wound healing promotion

“…1 Currently, widely applied traditional therapeutics such as surgery excision, chemotherapy and radiotherapy still suffer from several problems, including high risk of infection, severe adverse effects, undesirable drug resistance, great threat of recurring, and so on. [2][3][4] Photothermal therapy (PTT), a non-invasive treatment modality, utilizes photothermal agents to convert absorbed near-infrared (NIR) light into local hyperthermia for ablation of cancerous cells. [5][6][7] Benefiting from the high spatiotemporal accuracy of light, PTT minimized the adverse effects towards normal tissues and thereby exhibited significant advantages beyond conventional therapeutic modalities.…”

PAI/MRI Visualization of Tumor Derived Cellular Microvesicles with Endogenous Biopolymer Nanoparticles Modification

“…31 Moreover, melanin nanoparticles have many potential applications in biomedicine due to their properties including metal ion chelation and strong optical absorption in the near-infrared region. [32][33][34][35][36][37][38][39] Herein, water-soluble Gd-based melanin nanoparticles (MNP-Gd) have been constructed as an MRI/PAI dual-modal imaging contrast agent by a facile route. After modifying the TDMVs with the nanoparticles, the visualization of their biological distribution behavior is realized, which is of great significance for understanding the positioning distribution and metabolism of TDMVs in the body.…”