Issue 2, 2024

Re-engineered theranostic gold nanoparticles for targeting tumor hypoxia

Abstract

Developing nanovehicles for selective delivery of a radiation dose/drug to hypoxic tumors is a present-day clinical requirement for effective treatment of cancer. Herein, we describe our attempt to re-engineer the earlier reported lipoic acid-capped 177Lu-labeled nitroimidazole-decorated gold nanoparticles to favorably modulate their pharmacokinetics to reduce uptake in the reticuloendothelial system while retaining the uptake in tumors. Towards this, gold nanoparticles with PEG-chains terminated with 2-nitroimidazole and Bz-DOTA were synthesized [(DOTA)AuNP-PEG-2K-(2-NIM)]. Surface modification of the gold nanoparticles with PEG-2K and 2-nitroimidazole was confirmed through infrared spectroscopy. The conjugation of Bz-DOTA on the nanoparticle surface was confirmed by UV-Vis spectroscopy, which showed a peak at 260–280 nm corresponding to Bz-DOTA. The DLS analysis of gold nanoparticles showed an effective hydrodynamic diameter of 28.9 ± 1.50 nm with a zeta potential value of −20.62 ± 0.05 mV at pH 7.4. The nanoparticles were radiolabeled with lutetium-177 with >98% radiochemical purity. In vitro studies using radiolabeled nanoparticles ([177Lu]Lu-(DOTA)AuNP-PEG-2K-(2-NIM)) in CHO cells showed their 2-fold uptake under hypoxic conditions (at 4 h post incubation) compared to the radiolabeled nanoparticles without nitroimidazole units. The hypoxia selective uptake of the nanoparticles was further confirmed by flow cytometry using a fluorescent analogue (DOTA)AuNP-PEG-2K-(2-NIM)(FITC). It was, however, observed that hypoxic cell uptake of the PEG-2K capped nanoparticles was lower than that of their lipoic acid capped counterpart. In vivo biodistribution studies in tumor bearing Swiss mice demonstrated that PEGylation of nanoparticles could significantly reduce the uptake in the RES while retaining uptake in tumors albeit to a lesser extent.

Graphical abstract: Re-engineered theranostic gold nanoparticles for targeting tumor hypoxia

Supplementary files

Article information

Article type
Communication
Submitted
08 9月 2023
Accepted
19 12月 2023
First published
20 12月 2023
This article is Open Access
Creative Commons BY-NC license

Mater. Adv., 2024,5, 513-520

Re-engineered theranostic gold nanoparticles for targeting tumor hypoxia

S. Mittal, C. Kumar, M. B. Mallia and H. D. Sarma, Mater. Adv., 2024, 5, 513 DOI: 10.1039/D3MA00679D

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements