1. Doxorubicin Conjugated γ-Globulin Functionalised Gold Nanoparticles: A pH-Responsive Bioinspired Nanoconjugate Approach for Advanced Chemotherapeutics.
- Author
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Chauhan, Gaurav, Chopra, Vianni, Alvarado, América, Gómez Siono, Jocelyn, Madou, Marc, Martinez-Chapa, Sergio, and Kulkarni, Manish
- Subjects
anticancer hybrid ,doxorubicin ,gold nanoparticles ,hard protein corona ,nanobioconjugate ,pH responsive ,γ-Globulin - 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 coronas 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 pathways role in regulating cell fate, including apoptosis and necrosis, in response to these treatments. The pathways 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.
- Published
- 2024