Black phosphorus has emerged as a promising nanomaterial for biomedical applications due to its unique structural, electronic, and optical properties. Unlike other two-dimensional materials such as graphene oxide, black phosphorus exhibits a layer-dependent direct bandgap, high carrier mobility, and strong near-infrared absorption, making it particularly suitable for drug delivery, photothermal therapy, and biosensing. Its inherent biodegradability and biocompatibility further enhance its potential for clinical translation.

One of the most significant biomedical applications of black phosphorus is drug delivery. The material’s high surface area and tunable surface chemistry allow for efficient loading of therapeutic agents, including small-molecule drugs, nucleic acids, and proteins. The puckered lattice structure of black phosphorus provides abundant anchoring sites for covalent and non-covalent functionalization, enabling controlled drug release. Studies have demonstrated that black phosphorus nanosheets can be loaded with doxorubicin, achieving a loading efficiency exceeding 90%. The release kinetics can be modulated by external stimuli such as near-infrared light or pH changes, ensuring targeted delivery to tumor sites while minimizing systemic toxicity.

Photothermal therapy is another area where black phosphorus excels. The material exhibits strong absorption in the near-infrared region, which is optimal for deep tissue penetration. When exposed to NIR light, black phosphorus efficiently converts light energy into heat, inducing localized hyperthermia to ablate cancer cells. Research has shown that black phosphorus nanosheets can achieve a photothermal conversion efficiency of up to 28.4%, outperforming many conventional photothermal agents like gold nanorods and graphene oxide. Additionally, the photothermal effect can be combined with chemotherapy for synergistic anticancer effects, significantly improving therapeutic outcomes.

Biosensing applications of black phosphorus leverage its excellent electronic properties and surface sensitivity. The material’s high carrier mobility and tunable bandgap make it ideal for detecting biomolecules such as proteins, DNA, and small metabolites. Functionalized black phosphorus sensors have demonstrated high sensitivity and selectivity for biomarkers like prostate-specific antigen and glucose. The material’s ability to form heterostructures with other nanomaterials further enhances its sensing performance, enabling real-time monitoring of disease progression and treatment response.

A critical advantage of black phosphorus over other nanomaterials is its biodegradability. Unlike graphene oxide or carbon nanotubes, which persist in the body and raise long-term toxicity concerns, black phosphorus undergoes gradual degradation into phosphates and phosphonates, which are naturally metabolized. Studies have confirmed that black phosphorus nanosheets degrade completely within 48 to 72 hours in physiological conditions, reducing the risk of chronic inflammation or accumulation. This property is particularly advantageous for in vivo applications where clearance of the material is essential.

Biocompatibility studies have further validated the safety of black phosphorus for biomedical use. In vitro cytotoxicity assays on various cell lines, including HeLa and MCF-7 cells, have shown minimal toxicity at concentrations below 50 µg/mL. In vivo experiments in mice have also demonstrated good biocompatibility, with no significant inflammatory response or organ damage observed after systemic administration. Surface modifications with polymers like polyethylene glycol further enhance biocompatibility by preventing immune recognition and prolonging circulation time.

Despite these advantages, the potential toxicity of black phosphorus must be carefully evaluated. The degradation products, primarily phosphate ions, are generally considered safe, but excessive accumulation could disrupt cellular phosphate homeostasis. Studies have indicated that high doses of black phosphorus nanosheets may induce oxidative stress and membrane damage, emphasizing the need for dose optimization. Advanced surface coatings and controlled degradation strategies are being explored to mitigate these risks.

Compared to graphene oxide, black phosphorus offers several unique benefits. While graphene oxide lacks a bandgap and exhibits poor photothermal efficiency in the NIR-II window, black phosphorus provides tunable optoelectronic properties and superior photothermal performance. Additionally, graphene oxide’s non-biodegradability limits its clinical applicability, whereas black phosphorus degrades harmlessly. The anisotropic nature of black phosphorus also allows for directional drug loading and release, a feature absent in isotropic materials like graphene oxide.

In summary, black phosphorus holds immense potential for biomedical applications, particularly in drug delivery, photothermal therapy, and biosensing. Its biodegradability, biocompatibility, and superior physicochemical properties make it a compelling alternative to conventional nanomaterials. Ongoing research aims to address remaining challenges related to toxicity and large-scale production, paving the way for clinical adoption. As understanding of its biological interactions deepens, black phosphorus is poised to become a cornerstone of next-generation nanomedicine.