Virus-mimicking mesoporous organosilica nanocapsules with soft framework and rough surface for enhanced cellular uptake and tumor penetration
ABSTRACT: Enveloped virus with soft and rough shells have strong penetration ability for cells. Inspired by the unique structure of virus, we successfully construct a virus-mimicking mesoporous organosilica nanocapsules (denoted as VMONs) for the first time by decorating small-sized silica nanoparticles on soft mesoporous organosilica hollow spheres. TEM and SEM images reveal that the prepared VMONs possess uniform diameters (240 nm), soft framework, rough surface, and excellent dispersity. Quantitative nanomechanical mapping further demonstrates that the VMONs possess an extremely low Young’s modulus (36 MPa) and scraggly surface. In view of the successful construction of the virus-mimicking nanocapsules, the VMONs are further modified with human serum albumin (HSA) and Cy5.5-Maleimide (Mal-Cy5.5) to investigate their cell penetration ability. Flow cytometry analysis reveals that the internalization of VMONs@HSA-Cy5.5 increases 2.74-fold compared to that of conventional mesoporous nanosphere. Confocal laser scanning microscopy images show that the VMONs@HSA-Cy5.5 diffuses deeper for multicellular spheroids compared to both hard and soft mesoporous organosilica nanospheres. The penetration ability of the VMONs and SMONs increases 18.49 and 6.13-fold compared that of MONs at the depth of 60 µm. Thanks to the excellent cellular penetration ability, the virus-mimicking VMONs@HSA-Cy5.5 can effectively deliver anticancer drug doxorubicin (Dox) into drug resistant MCF-7/ADR human breast cancer cells and significantly enhances chemotherapeutic efficacy. Taken together, the constructed virus-mimicking organosilica nanocapsules with soft framework and rough surface possess strong cellular internalization and tumor penetration ability, providing an unique and effective nanoplatform for biomedical applications.