Effectiveness and safety of a nontargeted boost for a CXCR4-targeted magnetic hyperthermia treatment of cancer cells

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Vera Vilas-Boas (Author) Other; Begoña Espiña (Author) Other; Yury V. Kolen'ko (Author) Other; Manuel Banobre Lopez (Author) Other; Marina Brito (Author) Other; Verónica Martins (Author) Other; José Alberto Duarte (Author) FADEUP; Dmitri Y. Petrovykh (Author) Other; Paulo Freitas (Author) Other; Félix Carvalho (Author) FFUP

Journal

Title: ACS Omega

Vol. 4 No. 1

Pages: 1931-1940

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 5 Citations

Scientific classification

FOS: Social sciences

Other information

Authenticus ID: P-00Q-AP7

DOI: 10.1021/acsomega.8b02199

Abstract (EN): We investigate the effectiveness and safety of a novel magnetic hyperthermia (MHT) protocol, whereby a pretreatment with nontargeted magnetic nanoparticles (MNPs) is used to boost the subsequent iron loading of cancer cells by the targeted immuno-modified MNPs. As a model example, LN229 cancer cells express specific cell-surface receptors (CXCR4) at levels sufficient for diagnostic identification but insufficient for achieving 100% effective monotherapeutic MHT based on CXCR4-targeted MNPs. The nontargeted boost of the iron content overcomes this limitation of the targeted loading and is positively correlated with the maximum temperature reached during MHT treatment of LN229 cells. The effectiveness of the dual-population MHT strategy is validated by achieving a 100% lethal outcome for LN229 cancer cells 72 h after the treatment, while its safety is confirmed by the minimal cytotoxicity observed in control experiments with normal HK-2 cells or with an isotype-control targeting antibody. Systematic in vitro measurements thus demonstrate that the magnetic loading by targeted MNPs can be significantly increased by the nontargeted boost, even to double the iron concentration, while improving the effectiveness and maintaining the safety of MHT. This validation of the dual-population MHT strategy opens a novel materials-based pathway, unassisted by highly and nonselectively cytotoxic chemotherapeutic agents, to overcome the limited effectiveness of MHT for treating cancer cells that express only moderate levels of cell-surface receptors.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10