Issue 27, 2018

Towards potent but less toxic nanopharmaceuticals – lipoic acid bioconjugates of ultrasmall gold nanoparticles with an anticancer drug and addressing unit

Abstract

Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units. The application of lipoic acid enabled the control of the gold nanoparticle functionalities leading to enhanced solubility and allowing for attachment of both the folic acid and the cytotoxic drug, doxorubicin. More robust attachment of doxorubicin to the nanoparticle through the amide bond resulted in toxicity comparable with that of the drug alone, opening a new perspective for designing more potent, but less toxic nanopharmaceuticals. The increased uptake was accompanied by pronounced nuclear accumulation and observable cytotoxicity. Doxorubicin binding via covalent amide bonds enhanced stability of the whole drug vehicle and provided much better control over doxorubicin release in the cell environment, as compared to physical adsorption or pH sensitive bonding commonly used for anthracycline carriers. Confocal microscopy revealed that the bond was stable in the cytoplasm for 22 h. The ability to slow down the rate of drug release may be crucial for the application in sustained anticancer drug delivery. Biological analyses performed using MTT assay and confocal microscopy confirmed that the ultrasmall AuNPs with the lipoic acid derivative of folic acid exhibit relatively low cytotoxicity, however when loaded with a chemotherapeutic, they cause a significant reduction in the cell viability.

Graphical abstract: Towards potent but less toxic nanopharmaceuticals – lipoic acid bioconjugates of ultrasmall gold nanoparticles with an anticancer drug and addressing unit

Supplementary files

Article information

Article type
Paper
Submitted
05 Feb 2018
Accepted
15 Apr 2018
First published
19 Apr 2018
This article is Open Access
Creative Commons BY license

RSC Adv., 2018,8, 14947-14957

Towards potent but less toxic nanopharmaceuticals – lipoic acid bioconjugates of ultrasmall gold nanoparticles with an anticancer drug and addressing unit

M. Dzwonek, D. Załubiniak, P. Piątek, G. Cichowicz, S. Męczynska-Wielgosz, T. Stępkowski, M. Kruszewski, A. Więckowska and R. Bilewicz, RSC Adv., 2018, 8, 14947 DOI: 10.1039/C8RA01107A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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