Photo-tearable tape close-wrapped upconversion nanocapsules for near-infrared modulated efficient siRNA delivery and therapy

Abstract RNA interference (RNAi) has become an appealing therapeutic approach for cancer and other diseases. One key challenge is the effective protection of these small fragile biomolecules against complicated physiological environments as well as efficient on-demand release. Here we design a photo-tearable polymer tape close-wrapped nanocapsule for efficient NIR modulated siRNA delivery. The photo-tearable nanocapsules comprise core-shell upconversion nanoparticles (UCNPs) coated with mesoporous silica layer for loading of photosensitizer hypocrellin A (HA) and small interfering RNA (siRNA) against polo-like kinase 1 (PLK1), and covalently bound thin membranes of polyethylene glycol (PEG) via a synthesized photocleavable linker (PhL). Upon irradiation at 980 nm, the UCNPs produce UV emissions to break PhL and tear out PEG membrane for siRNA release, and blue emissions to activate HA for generating reactive oxygen species (ROS). The close PEG membrane wrapping not only guarantees the efficient intracellular photocleavage, but also extends the circulation time and protects the loaded cargos from leakage and degradation. The ROS assists endosomal escape of the loaded cargos, therefore effectively improves the gene silencing efficiency and the suppressions of cell proliferation in vitro and tumor growth in vivo. The proposed photo-tearable tape-wrapped nanocapsules have promising potential application in precision medicine.