Polycation–Carbon Nanohybrids with Superior Rough Hollow Morphology for the NIR-II Responsive Multimodal Therapy

Polymer-inorganic hybrid nanomaterials have attracted much attention for the multimodal cancer therapy, while it is still desirable to explore hybrids with superior morphologies for two or more therapeutic modalities. In this work, four types of carbon nanoparticles with distinct morphologies were prepared by an elaborate template-carbonization corrosion process and then functionalized with a similar amount of the superior polycationic gene vector, CD-PGEA [consisting of one β-cyclodextrin core (CD) and two cationic ethanolamine-functionalized poly(glycidyl methacrylate) (PGEA) arms] to evaluate the morphology-influenced gene and photothermal (PT) therapy. Benefiting from the starting rough hollow nanosphere (RHNS) core, the resultant nanohybrids RHNS-PGEA exhibited the highest gene transfection (including luciferase, fluorescent protein plasmid, and antioncogene p53) and NIR PT conversion efficiency among the four types of nanohybrids. Moreover, the efficient PT effect endowed RHNS-PGEA with PA imaging enhancement and an effective imaging guide for the tumor therapy. In addition, anticancer drug 10-hydroxy camptothecin was successfully encapsulated in RHNS with polycation coating, which also displayed the second near-infrared (NIR-II)-responsive drug release. Taking advantages of the superior gene delivery/PT effect and NIR-II-enhanced drug delivery, RHNS-PGEA realized a remarkable therapeutic effect of trimodal gene/PT/chemotherapy of malignant breast cancer treatment in vitro and in vivo. The present work offers a promising approach for the rational design of polymer-inorganic nanohybrids with superior morphology for the multimodal cancer therapy.