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; p. 2792
• 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 08-04-2020
• Subjects: Adsorption; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Proliferation - drug effects; Cell Survival - drug effects; Coculture Techniques; Drug Liberation; Drug Screening Assays, Antitumor; Durapatite - chemistry; Durapatite - pharmacology; Humans; Kinetics; Male; Nanoparticles - chemistry; Particle Size; Platinum - chemistry; Platinum - pharmacology; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Selenium - chemistry; Selenium - pharmacology; Stem Cells - drug effects; Surface Properties; Tumor Cells, Cultured
• ISSN: 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.