Development of cytosolic protein delivery platforms brings new possibilities for various incurable diseases. Strategies based on polymer/protein self-assembly have shown their potential in protein delivery. However, versatile photocontrolled platforms based on self-assembly for protein delivery are seldom reported. Herein, we report a boron-dipyrromethene (BODIPY)-modified polyamidoamine (PAMAM) with excellent photo-controllability and efficiency for the cytosolic delivery of various proteins. High serum stability was achieved by coating hyaluronic acid and human serum albumin on the surface of BODIPY-modified PAMAM/protein nanoparticles. The nanoparticles under green light irradiation allowed efficient intracellular delivery of multiple cargo proteins with different charges and molecular weights and promoted endosome escape. The study provides valuable guidance for the development of BODIPY derivative-based protein delivery systems and advances the research in intracellular protein delivery.

Here, we report a strategy to deliver drug nanoparticles into cells with nucleus-targeting ability under a spatiotemporal control. The nanoparticles were constructed through self-assembly of photoresponsive prodrugs and free drugs. By incorporating a nucleus localization sequence in the system, drug nanoparticles could be delivered into nuclei upon visible light irradiation. The drug nanoparticles showed high drug loading capacity and specific nucleus-targeting ability, which efficiently killed cancer cells. This self-assembly strategy could be applied to other hydrophobic drugs and targeting ligands for photo-controlled organelle-targeted drug delivery.

Stimuli-triggered targeting of drug delivery systems can both increase the therapeutic efficacy and lower toxicity by selectively delivering drugs at target sites with high specificity and efficiency. Light is a convenient and powerful stimulus for use in such drug delivery systems because it is readily available and noninvasive and offers excellent spatiotemporal control. The power and wavelength of light can be finely tuned for different photoresponsive systems to achieve efficient targeting at the tissue, cellular, or subcellular levels. Here, we have reviewed the various mechanisms for phototriggered targeting (phototargeting) of drug nanocarriers. We have discussed the three main phototargeting strategies: (1) targeting ligand activation; (2) particle size reduction; and (3) blood vessel disruption.