Tailoring Boron Nitride Nanomaterials for Cancer Therapy

Boron nitride (BN) nanomaterials are representative layered nanomaterials with alternatively linked boron and nitrogen atoms, including zero-dimensional (0D) nanoparticles, one-dimensional (1D) nanotubes, two-dimensional (2D) nanosheets and so on. Over the past years, our research has focused on tailoring BN nanomaterials for cancer therapy, such as chemotherapy and cancer immunotherapy, due to their good biocompatibility, high drug loading efficiency, unique chemical composition, and biological activity.<br/><br/>1) BN nanomaterials as carriers for chemotherapy drugs<br/>BN nanomaterials have great potential as carriers for chemotherapy drugs based on their low toxicity and high drug loading capacity. However, pristine BN nanomaterials suffer from high hydrophobicity, easy aggregation, and weak targeting ability, which limits their application as delivery systems. We have explored several approaches to solve these problems. i) Pristine BN nanotubes were oxidized, shortened, and modified with mesoporous silica to create core@shell structures to greatly improve their suspension ability and hydrophilic properties in an aqueous solution. ii) The perfectly water-soluble and porous BN nanomaterials, featuring unprecedentedly high hydroxylation degrees, were synthesized via an original and simple thermal substitution method. These hydroxylated BN nanomaterials can effectively load anticancer drugs (e.g., doxorubicin, DOX) up to contents three times exceeding their own weight. iii) In addition, BN nanotubes were functionalized with europium-doped sodium gadolinium fluoride to enable magnetically targeted chemotherapy. Under an external magnetic field, the cellular uptake of modified BN nanotubes by cancer cells was increased approximately 2-fold, and the modified BN nanotubes loaded with DOX exhibited significantly high chemotherapeutic efficacy, compared with those in the absence of magnetic field.<br/><br/>2) BN nanomaterials as boron reservoir for chemotherapy of prostate cancer<br/>Boron compounds have attracted attention as preventative and therapeutic agents for prostate cancer and other cancers. However, systemic administration of soluble boron compounds is associated with the drawbacks of short half-life period, low bioavailability, and limited effectiveness. We fabricated hollow BN nanospheres with controlled crystallinity and boron release. The optimized BN nanospheres effectively induced apoptosis and necrosis in both androgen-sensitive LNCap and androgen-independent DU-145 prostate cancer cells <i>in vitro</i>. <i>In vivo</i> experiments in subcutaneous tumor mouse models and orthotopic tumor growth models confirmed the antitumor efficacy of BN nanospheres. The work demonstrates that hollow BN spheres may function as a new agent for prostate cancer treatment.<br/><br/>3) BN nanomaterials as adjuvants for cancer immunotherapy<br/>Cancer immunotherapy seeks to harness the exquisite power of the immune system to fight against cancer. Inspired by the positive effects of boron supplementation on the immune system by promoting the production of Th1 cytokines, we investigated BN nanospheres as novel adjuvants for cancer vaccines to enhance the antitumor immunity. Cancer vaccines prepared with BN nanospheres exhibited much higher antitumor efficacy <i>in vivo</i> than those prepared with free boric acid, their carbon counterparts and commercially used alum adjuvants. Mechanistic studies showed that the addition of BN nanospheres significantly enhanced the antitumor immune responses by stimulating the secretion of Th1 cytokines, such as IL-2, IFN-γ and TNF-α, and increasing the cytotoxic CD8⁺ T cell population in lymphocytes. Histological section studies suggested that the addition of BN nanospheres can inhibit metastasis.