Development of a Light-Controlled Nanoplatform for Direct Nuclear Delivery of Molecular and Nanoscale Materials

Research on nanomedicines has rapidly progressed in the past few years. However, due to the limited size of nuclear pores (9–12 nm), the nuclear membrane remains a difficult barrier to many nucleus-targeting agents. Here, we report the development of a general platform to effectively deliver chemical compounds such as drug molecules or nanomaterials into cell nuclei. This platform consists of a polyamine-containing polyhedral oligomeric silsesquioxane (POSS) unit, a hydrophilic polyethylene glycol (PEG) chain, and the photosensitizer rose bengal (RB), which can self-assemble into nanoparticles (denoted as PPR NPs). Confocal fluorescence imaging showed that PPR NPs mainly located in lysosomes after cellular internalization. After mild light irradiation, however, PPR NPs effectively disrupted lysosomal structures by singlet oxygen (1O2) oxidation and substantially accumulated on nuclear membranes, which enabled further disruption of the membrane integrity and promoted their final nuclear entry. Next, we sel...