Abstract

Nanotechnology-based drug delivery provides a promising area for improving the efficacy of cancer treatments. Therefore, we investigate the potential of using quantum dots (QDs) as drug carriers for antitumor unsymmetrical bisacridine derivatives (UAs) to cancer cells. We examine the influence of QD–UA hybrids on the cellular uptake, internalization (Confocal Laser Scanning Microscope), and the biological response (flow cytometry and light microscopy) in lung H460 and colon HCT116 cancer cells. We show the time-dependent cellular uptake of QD–UA hybrids, which were more efficiently retained inside the cells compared to UAs alone, especially in H460 cells, which could be due to multiple endocytosis pathways. In contrast, in HCT116 cells, the hybrids were taken up only by one endocytosis mechanism. Both UAs and their hybrids induced apoptosis in H460 and HCT116 cells (to a greater extent in H460). Cells which did not die underwent senescence more efficiently following QDs–UAs treatment, compared to UAs alone. Cellular senescence was not observed in HCT116 cells following treatment with both UAs and their hybrids. Importantly, QDgreen/red themselves did not provoke toxic responses in cancer or normal cells. In conclusion, QDs are good candidates for targeted UA delivery carriers to cancer cells while protecting normal cells from toxic drug activities.

Highlights

  • At present, cancer is one of the most serious diseases in the world

  • We presented a nanoparticle-based drug delivery system using quantum dots (QDs) conjugated with unsymmetrical bisacridines (UAs), which have high antitumor activity

  • Confocal Laser Scanning Microscope (CLSM) analysis showed the increased cellular uptake of QD–Unsymmetrical bisacridine derivatives (UAs) hybrids, compared to UAs alone, in human lung H460 cells, which may have resulted from the co-operation of three endocytosis pathways: CME, CavME, and MP

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Summary

Introduction

Cancer is one of the most serious diseases in the world. Despite the development of new cancer therapies, including immunotherapy and photothermal therapy, traditional chemotherapy is still the main method for cancer treatment [1]. Effective methods of cancer therapy using conventional chemotherapeutic agents are still limited [2,3]. The most significant difficulties in conventional chemotherapy are poor bio-distribution to tumors, leading to toxic side effects in normal tissues and cells [4], as well as low drug solubility, the development of multiple drug resistances, and high dose requirements [5]. These issues can be potentially overcome through the delivery of anticancer drugs by nanoparticles (NPs) [6,7].

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