Black Phosphorus Quantum Dots Gated, Carbon‐Coated Fe3O4 Nanocapsules (BPQDs@ss‐Fe3O4@C) with Low Premature Release Could Enable Imaging‐Guided Cancer Combination Therapy

Combination therapies for tumors based on different therapeutic approaches should try to improve treatment efficacy, but also to reduce side‐effects related to the exogenous stimulus and premature release. In the following study, we established and validated a pH/near‐infrared (NIR)/glutathione (GSH)/‐responsive multifunctional disulfide cross‐linked Fe3O4@C nanocarriers (ss‐Fe3O4@C NCs) with black phosphorus quantum dots (BPQDs) as a capping agent. BPQDs and carbon shell of Fe3O4@C nanoparticles (NPs) were used as a photothermal agents, while the inner empty nucleus that allows for a high drug payload served as an effective drug carrier. These magnetofluorescent BPQDs@DOX@ss‐Fe3O4@C NPs were conjugated with a targeting aptamer (epidermal growth factor receptor: EGFR), denoted as BPQDs@DOX@ss‐Fe3O4@C‐EGFR NPs, for targeting dual modal magnetic resonance (MR)/fluorescence imaging. The synthetic NCs showed that drug release was dependent on pH, near‐infrared (NIR), and intracellular GSH levels, with minimum systemic release in the blood and maximum drug release within the tumors. Also, the photothermal effect resulting from the Fe3O4@C NPs and BPQDs upon application to NIR light caused a rapid rise in local temperature, which accounted for the highest enhancement of cell cytotoxicity. Thus, a theranostic system consisting of BPQDs@DOX@ss‐Fe3O4@C‐EGFR NPs is shown to generate excellent advantages in combined chemotherapy/photothermal therapy (PTT) with minimal side effects.