Platinum-loaded, selenium-doped hydroxyapatite nanoparticles selectively reduce proliferation of prostate and breast cancer cells co-cultured in the presence of stem cells

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Vol. 8; no. 14; pp. 2792 - 284
• Main Authors: Barbanente, Alessandra, Nadar, Robin A, Esposti, Lorenzo Degli, Palazzo, Barbara, Iafisco, Michele, van den Beucken, Jeroen J. J. P, Leeuwenburgh, Sander C. G, Margiotta, Nicola
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 08.04.2020
• Subjects: Adsorption; adverse effects; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biocompatibility; biocompatible materials; Biomaterials; Biomedical materials; Bone marrow; Bone tumors; Breast cancer; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell number; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemotherapy; coculture; Coculture Techniques; Drug Liberation; Drug resistance; Drug Screening Assays, Antitumor; drug therapy; drug toxicity; Durapatite - chemistry; Durapatite - pharmacology; human diseases; Humans; Hydroxyapatite; Kinetics; Male; Metastases; Metastasis; nanocrystals; Nanoparticles; Nanoparticles - chemistry; neoplasm cells; Particle Size; patients; Platinum; Platinum - chemistry; Platinum - pharmacology; Prostate; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Selectivity; Selenite; Selenium; Selenium - chemistry; Selenium - pharmacology; Side effects; Stem cells; Stem Cells - drug effects; Surface Properties; Toxicity; Tumor Cells, Cultured
• ISSN: 2050-750X; 2050-7518; 2050-7518
• DOI: 10.1039/d0tb00390e

Chemotherapeutic treatment of patients with bone tumors or bone metastases often leads to severe side effects such as high drug toxicity, lack of tumor specificity and induced drug resistance. A novel strategy to treat early stages of bone metastases involves local co-delivery of multiple chemotherapeutic agents to synergistically improve the curative effect and overcome shortcomings of traditional chemotherapy. Herein we show that selenite-doped hydroxyapatite nanoparticles loaded with a hydroxyapatite-binding anti-tumor platinum complex (PtPP-HASe) selectively reduce proliferation of cancer cells without reducing proliferation of bone marrow stem cells. These PtPP-HASe particles were nanocrystalline with selenium (Se) and platinum (Pt) contents ranging between 0-10 and 1.5-3 wt%, respectively. Release kinetics of Se and Pt from PtPP-HASe nanoparticles resulted in a cumulative release of ∼10 and ∼66 wt% after 7 days, respectively. At a Pt/Se ratio of 8, released Pt and Se species selectively reduced cell number of human prostate (PC3) and human breast cancer cells (MDA-MB-231) by a factor of >10 with limited effects on co-cultured human bone marrow stem cells (hBMSc). These novel nanoparticles demonstrate high anti-cancer selectivity, which offers ample opportunities for the design of novel biomaterials with potent and selective chemotherapeutic efficacy against cancer cells. Selenite-doped hydroxyapatite nanoparticles loaded with an anti-tumor Pt( ii )-pyrophosphate complex were prepared to treat bone tumors and metastases by local release of multiple chemotherapeutic agents.