The multifunctional role of hydroxyapatite nanoparticles as an emerging tool in tumor therapy.

Hydroxyapatite nanoparticles (HANPs) are well-known nanomaterials for bone regeneration or repair. In recent years, HANPs have emerged as a potential tool in tumor therapy because of the numerous advantages the nanoparticles offer, including the diverse physicochemical properties, the selective anti-tumor effect, intrinsic immunomodulatory activity, ability to reverse of drug or immune tolerance, allowance of ion substation, good drug-loading capabilities, etc. Notably, the physicochemical properties of the particles, such as size and shape, significantly influence their anti-tumor efficacy. Therefore, to offer a comprehensive understanding of the key properties of HANPs and the involving molecular mechanisms, and provide crucial cues for rational design and development of novel HANPs-based anti-tumor platforms, this review summarizes various synthesis methods of HANPs with controlled physiochemical characteristics and highlights the multifaceted effects such as interactions with tumor cells and immune cells, regulation of the tumor microenvironment (TME), overcoming drug or immune resistance, and their potentials as effective drug carriers. This review also outlines the emerging strategies leveraging HANPs for tumor therapy and diagnostic imaging. At last, we discuss the challenges HANPs face when used for tumor treatment. STATEMENT OF SIGNIFICANCE: Hydroxyapatite nanoparticles (HANPs) have emerged as a promising tool in tumor therapy without compromising biocompatibility. This review highlights the unique and multifaceted features of HANPs in tumor therapy, including the selective induction of tumor cell apoptosis, engagement in immune regulation, reversal of drug or immune resistance, and the loading of diverse anti-tumor drugs or biomaterials. Additionally, this review emphasizes the influence of the intrinsic physicochemical properties of HANPs on their anti-tumor activity, and explores the emerging strategies that leverage HANPs for tumor therapy and diagnostic imaging. In summary, this work aims to provide a comprehensive and deep understanding of the role of HANPs in tumor therapy and is significant for the improved design of HANP-based platforms for tumor therapy.