Abstract

Purpose: K-RAS is the most common mutated oncogene associated with Non-Small-Cell Lung Cancer (NSCLC). So far, there are no promising chemotherapies for the direct inhibition of K-RAS, and considered to be undruggable. In this work, we have introduced a new platinum-based cyanoximate complex, Pt(MCO)2, as an anti-cancer drug to enhance the therapeutic efficacy of Hsp90 inhibitor drug, ganetespib for the combination therapy of NSCLC. Methods: We have synthesized polyacrylic acid (PAA)-coated magnetic nanoparticles (MNPs) and used as drug delivery system. These MNPs were decorated with folic acid in order to target folate receptor-expressing NSCLC. The individual and combination of drugs as well as an optical dye DiI were co-encapsulated successfully inside the PAA-coating of MNPs to evaluate synergistic treatment option for NSCLC. The magnetic resonance (MR) and optical imaging modalities assisted for the monitoring drug loading and NSCLC treatment. Results: To evaluate the therapeutic efficacy of these customized MNPs, various cell-based assays including cell viability, apoptosis and necrosis, cell migration, comet and ROS experiments were performed. Results showed minimal toxicity for functional MNPs with no therapeutic drug and more than 60% cell death within 48 h of treatment, when single drug was encapsulated. Importantly, more than 90% cells were dead when both drugs were delivered. Overall, the results indicated that the Pt(MCO)2 drug enhances the therapeutic efficacy of ganetespib by more than 30% toxicity towards the targeted treatment of NSCLC, while showed minimal toxicity to the normal healthy tissues. Conclusion: We successfully developed new dual-modal magnetic nanomedicines for the rapid and controlled release of combination of drugs for the effective treatment of NSCLC. The MR and fluorescence modalities help monitoring the delivery of drugs, where the new platinum-based drug Pt(MCO)2 synergizes the therapeutic efficacy of ganetespib.

Department(s)

Chemistry and Biochemistry

Document Type

Article

DOI

https://doi.org/10.7150/ntno.28468

Rights Information

© Ivyspring International Publisher. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Keywords

Ganetespib, Non-Small-Cell Lung Cancer, Platinum-based cyanoximate complex

Publication Date

1-1-2019

Journal Title

Nanotheranostics

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