Effective cancer treatment often depends on whether therapeutic drugs can reach their intended targets inside tumor cells. For many widely used anticancer drugs, the cell nucleus is the key site of action. However, after entering cells, these drugs are frequently trapped by multiple intracellular barriers, greatly limiting their therapeutic efficacy.
To address this long-standing challenge, the research team developed a light-responsive nanoassembly that enables precise and controllable drug delivery inside tumor cells. By co-assembling a polymeric prodrug capable of releasing the anticancer agent camptothecin with an amphiphilic photosensitizer, the researchers constructed a supramolecular nanoassembly that remains stable under normal conditions but becomes activated upon near-infrared light exposure. When illuminated, the nanoassembly generates reactive oxygen species that trigger on-demand drug release and facilitate escape from intracellular vesicles, allowing the drug to reach the cytosol more efficiently. Importantly, the light-induced reactions also increase the permeability of the nuclear membrane, enabling the drug to accumulate rapidly in the cell nucleus, where it can exert its full therapeutic effect. As a result of this self-accelerating delivery process, phototherapy and chemotherapy act synergistically to produce a markedly enhanced anticancer response. In breast cancer models, the strategy achieved strong tumor suppression while effectively inhibiting tumor spread, without causing noticeable systemic toxicity.
This study demonstrates a new chemically driven approach to achieve spatiotemporally controlled subcellular drug delivery. The findings provide valuable insights for the future design of safer and more precise nanoassembly-based cancer therapies.
Science Bulletin