Pal, M and Bera, A and Masarkar, N and Upadhyay, A and Mukherjee, S and Roy, M (2024) Targeted Chemo-Phototherapy in Red Light with Novel Doxorubicin and Iron(III) Complex-Functionalized Gold Nanoconjugate (Dox-Fe@FA-AuNPs). In: Chemistry - An Asian Journal .
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Abstract
The anticancer efficacy of doxorubicin, an anthracycline-based and FDA-approved chemotherapeutic drug, is significantly hindered by acquired chemoresistance and severe side effects despite its potent anticancer properties. To overcome these challenges, we developed an innovative therapeutic formulation that integrates targeted chemotherapy and phototherapy within a single platform using gold nanoparticles (AuNPs). This novel nanoconjugate, designated as Dox-Fe@FA-AuNPs, is co-functionalized with folic acid, doxorubicin, and an iron(III)-phenolate/carboxylate complex, enabling cancer-specific drug activation. Here, we report the synthesis, characterization, and comprehensive physico-chemical and biological evaluations of Dox-Fe@FA-AuNPs. The nanoconjugate exhibited excellent solubility, stability, and enhanced cellular uptake in folate receptor-positive cancer cells. The nanoconjugate was potently cytotoxic against HeLa and MDA-MB-231 cancer cells (HeLa: 105.5±16.52 μg mL�1; MDA-MB-231: 112.0±12.31 μg mL�1; MDA-MB-231 (3D): 156.31±19.35 μg mL�1) while less cytotoxic to the folate(�) cancer cells (MCF-7, A549 and HepG2). The cytotoxicity was attributed to the pH-dependent release of doxorubicin, which preferentially occurs in the acidic tumor microenvironment. Additionally, under red light irradiation, the nanoconjugate generated ROS, inducing caspase-3/7-dependent apoptosis with a photo-index (PI) >50, and inhibited cancer cell migration. Our findings underscore the potential of Dox-Fe@FA-AuNPs as a highly effective and sustainable platform for targeted chemo-phototherapy. © 2024 Wiley-VCH GmbH.
Item Type: | Journal Article |
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Publication: | Chemistry - An Asian Journal |
Publisher: | John Wiley and Sons Ltd |
Additional Information: | The copyright for this article belongs to publishers. |
Keywords: | Biosynthesis; Carboxylation; Chemoradiotherapy; Chemotherapy; Controlled drug delivery; Cytotoxicity; Drug interactions; Gallium compounds; Metal nanoparticles; Nanoconjugates; pH sensors; Targeted drug delivery, Co-functionalized gold nanoparticle; Cytotoxicity in drug resistant MDA-MB-231 cell (2d and 3d); Doxorubicin; Folate receptor; Folate receptor targeting; Functionalized gold nanoparticles; MDA-MB-231; pH sensitive; Ph sensitive doxorubicin release; Phototherapy; Receptor targeting; Targeted chemo-phototherapy, Gold nanoparticles |
Department/Centre: | Division of Chemical Sciences > Inorganic & Physical Chemistry |
Date Deposited: | 15 Sep 2024 09:14 |
Last Modified: | 15 Sep 2024 09:14 |
URI: | http://eprints.iisc.ac.in/id/eprint/86091 |
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