Title: Study on the effect of carrier-free dual-drug nanocrystals against colon cancer cells

Authors: Qing Jiang; Yi Zhang; Yilan Qiu; Meifang Quan; Shanyi Yang; Feiyi Chu; Rong Wang; Zhichao Ye; Xiaojun Tao; Rushi Liu

Addresses: Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China ' Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China ' School of Life Science, Hunan Normal University, Changsha 410018, China ' Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China ' Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China ' Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China ' Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China ' Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China ' Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China ' Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China

Abstract: Nano-delivery systems are often used for targeted therapy of tumours, but a single anti-tumour drug often causes drug resistance in tumour cells, thereby reducing the effectiveness of the drug in chemotherapy. Therefore, in order to overcome the drug resistance of tumour cells, nano-formulations of combined drugs have emerged. This work aims to design a carrier-free dual drug-loaded nanocrystalline HCPT-DOX NCs, and verify its possibility of treating colon cancer through experiments. And through the comparison with a single drug, it highlights its advantages in the treatment of colon cancer. The synthesised HD NCs are characterised by dynamic light scattering (DLS), and the best synthesis ratio is selected. Through the drug release experiment, the release efficiency of a single drug in HD NCs is explored. Through MTT experiment, cell scratch experiment, cell cloning experiment, etc., the possibility of HD NCs in the treatment of colon cancer at the cellular level is discussed. The HCPT/DOX (HD) molar ratio of 1:1 is the best choice for the preparation of analytically valuable nanocrystals. Drug release experiments showed that the cumulative release rates of HCPT and DOX in HD NCs at 48 hours were 94.03% and 74.15%, respectively. MTT experiments of the colon cancer cell HCT116 and RKO showed a stronger synergistic inhibitory in low-concentration HD NCs than in drugs that underwent a simple physical mixing, and the RKO cells exhibited a more obvious effect. HD NCs could significantly inhibit colony formation of colon cancer cells in cell cloning experiments. Cell migration experiments showed that drug combination therapy of HD NCs could effectively inhibit the migration of cancer cells. By cell uptake experiments, it was determined that at the same concentration, the drug absorption of HD NCs was much higher than that of the free drug. HD NCs with appropriate particle size can be synthesized at a certain feeding ratio. The dual-drug-loaded HD NCs showed better anti-tumour effects than a single drug and a simple mixture of two drugs.

Keywords: nanocrystals; doxorubicin 10-Hydroxycamptothecin synergistic inhibition; colon cancer cells.

DOI: 10.1504/IJNT.2022.129765

International Journal of Nanotechnology, 2022 Vol.19 No.12, pp.1158 - 1176

Received: 29 Jun 2021
Accepted: 09 Nov 2021

Published online: 25 Mar 2023 *

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