Functionalized hydroxyapatite nanocomposites for localized drug delivery in bone cancer

Bone cancer and especially osteosarcoma is one disease that has proven to be a challenging therapeutic area because of poor prognosis, systemic drug toxicity, and limited response to conventional therapy. As an alternative method of treatment delivery, the localized drug delivery systems have come up promising with controlled release, lesser side effects and better therapeutic results. Hydroxyapatite (HAp), which is a calcium phosphate mineral that occurs naturally and demonstrates high biocompatibility as well as osteoconductivity, has attracted a lot of interest in bone tissue engineering and specific drug delivery. Nevertheless, there are inherent shortcomings of it such as brittle and low drug loading capacity (typically 2–10 wt%), which demand functionalization strategies. Coatings with polymers (PEG, chitosan, PLGA), inorganic ions (Zn, Ag, Sr), and carbon-based nanomaterials (graphene, CNTs) have been demonstrated to increase mechanical strength, drug encapsulation and release kinetics (enhancing loading efficiency up to 60–85% and prolonging release over 7–30 days). Nanocomposites constructed by HAp through co-precipitation, sol-gel, and hydrothermal techniques have been shown to deliver anticancer agents including doxorubicin, cisplatin and methotrexate with control. Additional targeting techniques such as ligand-mediated delivery, pH/enzyme-responsive release, and bone-seeking agents such as bisphosphonates further enhance targeting. The results of preclinical in vitro and in vivo studies suggest encouraging cytotoxicity against cancer cells, biocompatibility (osteoblast viability often >90%), and sustained drug delivery, but challenges to translational scalability, reproducibility and clinical validation exist. Smart stimuli-responsive carriers, theranostic integration and individualized medicine strategy should be investigated in the future, with functionalized HAp nanocomposites being the advanced option in the next generation of localized bone cancer therapy platforms.