Black Phosphorus Quantum Dots Gated, Carbon-Coated Fe₃O₄ Nanocapsules (BPQDs@ss-Fe₃O_4@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 Fe ₃ O ₄ @C nanocarriers (ss-Fe ₃ O ₄ @C NCs) with black phosphorus quantum dots (BPQDs) as a capping agent. BPQDs and carbon shell of Fe ₃ O ₄ @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-Fe ₃ O ₄ @C NPs were conjugated with a targeting aptamer (epidermal growth factor receptor: EGFR), denoted as BPQDs@DOX@ss-Fe ₃ O ₄ @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 Fe ₃ O ₄ @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-Fe ₃ O ₄ @C-EGFR NPs is shown to generate excellent advantages in combined chemotherapy/photothermal therapy (PTT) with minimal side effects.