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Updated: Sep 12, 2025
Hydroquinone Based Synthesis of Gold Nanorods
Published on: August 10, 2016
Hydroxyl-augmented gold nanorods via lactone ring-opening alleviate cisplatin nephrotoxicity through Nrf2 activation
Chunyan Fang1, Yueming Cai1, Cui He2
1School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, PR China.
Abstract:
Cisplatin-induced acute kidney injury (AKI) epitomizes a critical barrier and paradox in cancers, where dose-limiting nephrotoxicity propelled by oxidative cascades lacks targeted interventions. This pressing clinical dilemma underscores the paramount need for kidney injury mitigation, while existing therapeutic strategies fail to achieve it due to inadequate efficacy and specificity. Here, we introduce a lactone ring-opening chemistry approach to amplify hydroxyl-driven redox modulation on gold nanorods (Au-M NRs), addressing the unmet need for precision antioxidant delivery. Specifically, the sequential functionalization of gold nanorods with thiolated polyethylene glycol amine (HS-PEG2000-NH2) and 5,8-dihydroxypsoralen (5,8-DHP) triggered a structural transformation, cleaving the six-membered lactone ring of 5,8-DHP and generating an additional phenolic hydroxyl group. In cisplatin-challenged HK-2 cells, hydroxyl-enriched Au-M markedly attenuated reactive oxygen species (ROS) level and activated Keap1/Nrf2 pathway, evidenced by upregulated SOD and antioxidant Nqo1 expression alongside suppressed MDA and prooxidant Nox2 levels. SiNrf2 transfection severely abrogated the cytoprotective effects of Au-M, while Nrf2 overexpression synergistically enhanced the anti-apoptotic efficacy of Au-M in renal tubular epithelial cells. Mirroring cellular outcomes, the Au-M nanosystem elicited potent renoprotection via Nrf2-orchestrated transcriptional reprogramming in vivo, concurrently preserving the integrity and safety of healthy tissues. Critically, Au-M NRs conferred sustained protection in chronic exposure models, exhibited biocompatibility upon repeated dosing, and accelerated renal recovery, affirming their long-term therapeutic viability. This lactone-to-phenol conversion strategy pioneers a topology-guided paradigm for redox homeostasis regulation beyond AKI, establishing a transformative platform to harness natural product derivatization in combating organ-specific oxidative injury.
Insights
A novel gold nanorod (Au-M NR) system effectively mitigates cisplatin-induced acute kidney injury (AKI) by enhancing antioxidant delivery. This approach targets oxidative stress, offering a promising strategy for kidney protection in cancer therapy.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Toxicology
Background:
- Cisplatin chemotherapy causes dose-limiting acute kidney injury (AKI) due to oxidative stress, with limited targeted interventions.
- Existing therapies for nephrotoxicity lack efficacy and specificity, highlighting the need for novel renoprotective strategies.
Purpose of the Study:
- To develop a precision antioxidant delivery system using gold nanorods (Au-M NRs) to mitigate cisplatin-induced AKI.
- To investigate the mechanism of action involving hydroxyl-driven redox modulation and the Keap1/Nrf2 pathway.
Main Methods:
- Functionalization of gold nanorods with polyethylene glycol amine and 5,8-dihydroxypsoralen, inducing lactone ring-opening to create hydroxyl groups.
- Evaluation of hydroxyl-enriched Au-M NRs in cisplatin-treated HK-2 cells and in vivo mouse models.
- Assessment of reactive oxygen species (ROS) levels, antioxidant gene expression (SOD, Nqo1), and prooxidant markers (MDA, Nox2).
Main Results:
- Hydroxyl-enriched Au-M NRs significantly reduced ROS levels and activated the Keap1/Nrf2 antioxidant pathway in renal cells.
- Au-M NRs demonstrated potent in vivo renoprotection, preserving kidney integrity and promoting recovery in chronic exposure models.
- The nanosystem exhibited biocompatibility and long-term therapeutic viability with sustained protection upon repeated dosing.
Conclusions:
- The lactone-to-phenol conversion strategy on gold nanorods provides a novel platform for targeted antioxidant delivery against AKI.
- Au-M NRs offer a promising therapeutic approach for combating cisplatin-induced nephrotoxicity via Nrf2-mediated mechanisms.
- This topology-guided paradigm holds potential for broader applications in managing organ-specific oxidative injuries.
