From synthesis to application: A comprehensive review of black phosphorus in biomedical fields with a focus on cancer therapy

Black phosphorus (BP) is the most stable form of phosphorus and is gaining a lot of attention as a two-dimensional (2D) material for use in biomedical fields. Thanks to its unique anisotropic properties, impressive ability to convert light into heat, high carrier mobility, and natural biodegradability, BP holds great promise for applications like drug delivery, biosensing, and particularly in cancer treatment, including photothermal and photodynamic therapies. Recent reports also demonstrate synergy between BP platforms and immune checkpoint blockade such as BP-based photothermal platform combined with αCD47-mediated immune checkpoint inhibition for multimode cancer immunotherapy, and immune memory formation. Moreover, immunoengineering strategies such as tumor antigen-coated BP nanovaccines, have been shown to synergize photothermal-immunotherapeutic effects. New evidence also supports the biosafety, pharmacokinetics, and effective therapeutic use of BP nanostructures as guidance for their clinical application. However, one major hurdle is its quick degradation when exposed to normal environmental and physiological conditions, which poses a challenge for clinical use. This review takes a deep dive into the various methods for synthesizing BP, both top-down and bottom-up, and highlights recent progress in techniques aimed at enhancing its stability through passivation and surface modification. It also focuses on the biomedical and cancer-related uses of BP nanomaterials. The review thoroughly discusses key challenges, such as the limited information on biocompatibility and sensitivity to environmental factors. Lastly, it provides insights into future directions for overcoming these obstacles to accelerate the development of BP-based solutions in cancer therapy and other areas of biomedicine. • Drug delivery applications are supported by BP's high surface area and optical anisotropy. • Rapid BP breakdown and inadequate biocompatibility are major obstacles. • Black phosphorus has potential applications in medication administration and cancer treatment. • Techniques for fabricating scalable BP nanosheets are available via top-down and bottom-up approaches. • The environmental stability of BP is improved by functionalization through binding or coating.