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Pharmaceutics
Volume 16
Issue 2
10.3390/pharmaceutics16020208
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Article

Doxorubicin Conjugated γ-Globulin Functionalised Gold Nanoparticles: A pH-Responsive Bioinspired Nanoconjugate Approach for Advanced Chemotherapeutics

by
Gaurav Chauhan
1,*,†,
Vianni Chopra
1,†,
América García Alvarado
1,
Jocelyn Alexandra Gómez Siono
1,
Marc J. Madou
1,2,
Sergio Omar Martinez-Chapa
1 and
Manish M. Kulkarni
3,*
1
School of Engineering and Sciences, Tecnologico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, Monterrey 64849, NL, Mexico
2
Department of Mechanical and Aerospace Engineering, University of California Irvine, Irvine, CA 92697, USA
3
Centre for Nanoscience, Indian Institute of Technology Kanpur, Kanpur 208016, India
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Pharmaceutics 2024, 16(2), 208; https://doi.org/10.3390/pharmaceutics16020208
Submission received: 10 October 2023 / Revised: 13 December 2023 / Accepted: 13 December 2023 / Published: 31 January 2024
(This article belongs to the Special Issue Advanced Technologies for Nanomedicines)
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Abstract

Developing successful nanomedicine hinges on regulating nanoparticle surface interactions within biological systems, particularly in intravenous nanotherapeutics. We harnessed the surface interactions of gold nanoparticles (AuNPs) with serum proteins, incorporating a γ-globulin (γG) hard surface corona and chemically conjugating Doxorubicin to create an innovative hybrid anticancer nanobioconjugate, Dox-γG-AuNPs. γG (with an isoelectric point of ~7.2) enhances cellular uptake and exhibits pH-sensitive behaviour, favouring targeted cancer cell drug delivery. In cell line studies, Dox-γG-AuNPs demonstrated a 10-fold higher cytotoxic potency compared to equivalent doxorubicin concentrations, with drug release favoured at pH 5.5 due to the γ-globulin corona’s inherent pH sensitivity. This bioinspired approach presents a novel strategy for designing hybrid anticancer therapeutics. Our study also explored the intricacies of the p53-mediated ROS pathway’s role in regulating cell fate, including apoptosis and necrosis, in response to these treatments. The pathway’s delicate balance of ROS emerged as a critical determinant, warranting further investigation to elucidate its mechanisms and implications. Overall, leveraging the robust γ-globulin protein corona on AuNPs enhances biostability in harsh serum conditions, augments anticancer potential within pH-sensitive environments, and opens promising avenues for bioinspired drug delivery and the design of novel anticancer hybrids with precise targeting capabilities.
Keywords: gold nanoparticles; hard protein corona; γ-Globulin; doxorubicin; nanobioconjugate; pH responsive; anticancer hybrid gold nanoparticles; hard protein corona; γ-Globulin; doxorubicin; nanobioconjugate; pH responsive; anticancer hybrid

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MDPI and ACS Style

Chauhan, G.; Chopra, V.; Alvarado, A.G.; Gómez Siono, J.A.; Madou, M.J.; Martinez-Chapa, S.O.; Kulkarni, M.M. Doxorubicin Conjugated γ-Globulin Functionalised Gold Nanoparticles: A pH-Responsive Bioinspired Nanoconjugate Approach for Advanced Chemotherapeutics. Pharmaceutics 2024, 16, 208. https://doi.org/10.3390/pharmaceutics16020208

AMA Style

Chauhan G, Chopra V, Alvarado AG, Gómez Siono JA, Madou MJ, Martinez-Chapa SO, Kulkarni MM. Doxorubicin Conjugated γ-Globulin Functionalised Gold Nanoparticles: A pH-Responsive Bioinspired Nanoconjugate Approach for Advanced Chemotherapeutics. Pharmaceutics. 2024; 16(2):208. https://doi.org/10.3390/pharmaceutics16020208

Chicago/Turabian Style

Chauhan, Gaurav, Vianni Chopra, América García Alvarado, Jocelyn Alexandra Gómez Siono, Marc J. Madou, Sergio Omar Martinez-Chapa, and Manish M. Kulkarni. 2024. "Doxorubicin Conjugated γ-Globulin Functionalised Gold Nanoparticles: A pH-Responsive Bioinspired Nanoconjugate Approach for Advanced Chemotherapeutics" Pharmaceutics 16, no. 2: 208. https://doi.org/10.3390/pharmaceutics16020208

APA Style

Chauhan, G., Chopra, V., Alvarado, A. G., Gómez Siono, J. A., Madou, M. J., Martinez-Chapa, S. O., & Kulkarni, M. M. (2024). Doxorubicin Conjugated γ-Globulin Functionalised Gold Nanoparticles: A pH-Responsive Bioinspired Nanoconjugate Approach for Advanced Chemotherapeutics. Pharmaceutics, 16(2), 208. https://doi.org/10.3390/pharmaceutics16020208

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