In Vitro Assessment of a Gallium-Doped Glass Polyalkenoate Cement: Chemotherapeutic Potential, Cytotoxicity and Osteogenic Effects

Abstract

Metastatic bone lesions are often osteolytic, which causes advanced-stage cancer sufferers to experience severe pain and an increased risk of developing a pathological fracture. Gallium (Ga) ion possesses antineoplastic and anti-bone resorption properties, suggesting the potential for its local administration to impede the growth of metastatic bone lesions. This study investigated the chemotherapeutic potential, cytotoxicity, and osteogenic effects of a Ga-doped glass polyalkenoate cement (GPC) (C-TA2) compared to its non-gallium (C-TA0) counterpart. Ion release profiles revealed a biphasic pattern characterized by an initial burst followed by a gradually declining release of ions. C-TA2 continued to release Ga steadily throughout the experimentation period (7 d) and exhibited prolonged zinc (Zn) release compared to C-TA0. Interestingly, the Zn release from both GPCs appeared to cause a chemotherapeutic effect against H1092 lung cancer cells in vitro, with the prolonged Zn release from C-TA2 extending this effect. Unfortunately, both GPCs enhanced the viability of HCC2218 breast cancer cells, suggesting that the chemotherapeutic effects of Zn could be tied to cellular differences in preferred Zn concentrations. The utilization of SAOS-2 and MC3T3 cell lines as bone cell models yielded conflicting results, with the substantial decline in MC3T3 viability closely associated with silicon (Si) release, indicating cellular variations in Si toxicity. Despite this ambiguity, both GPCs exhibited harmful effects on the osteogenesis of primary rat osteoblasts, raising concerns about excessive burst Zn release. While Ga/Zn-doped GPCs hold promise for treating metastatic bone lesions caused by lung cancers, further optimization is required to mitigate cytotoxicity on healthy bone.

Department(s)

Chemical and Biochemical Engineering

Comments

Natural Sciences and Engineering Research Council of Canada, Grant RGPIN-2019-04634

Keywords and Phrases

bone metastasis; cancer; drug delivery; glass polyalkenoate cement

International Standard Serial Number (ISSN)

1748-605X; 1748-6041

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2024 IOP Publishing, All rights reserved.

Publication Date

01 Sep 2024

PubMed ID

38917820

Link to Full Text

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