DataVXACS Applied Materials & InterfacesPaper
journal article·2024-07-10

Glomerulus-Targeted ROS-Responsive Polymeric Nanoparticles for Effective Membranous Nephropathy Therapy

Ling Guo, Hanyu Yan, Qinqin Gong, Weili Zheng, Liang Zhong, Tao Gong, Xun Sun, Zhirong Zhang, Yuan Ping, Zilan Zhu, Jian Xu, Yongping Zhang

ACS Applied Materials & Interfaces· Volume 16· Issue 27
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Source abstract

Abstract

Membranous nephropathy (MN) is a common immune-mediated glomerular disease that requires the development of safe and highly effective therapies. Celastrol (CLT) has shown promise as a therapeutic molecule candidate, but its clinical use is currently limited due to off-target toxicity. Given that excess levels of reactive oxygen species (ROS) contributing to podocyte damage is a key driver of MN progression to end-stage renal disease, we rationally designed ROS-responsive cationic polymeric nanoparticles (PPS-CPNs) with a well-defined particle size and surface charge by employing poly(propylene sulfide)-polyethylene glycol (PPS-PEG) and poly(propylene sulfide)-polyethylenimine (PPS-PEI) to selectively deliver CLT to the damaged glomerulus for MN therapy. Experimental results show that PPS-CPNs successfully crossed the fenestrated endothelium, accumulated in the glomerular basement membrane (GBM), and were internalized by podocytes where rapid drug release was triggered by the overproduction of ROS, thereby outperforming nonresponsive CLT nanotherapy to alleviate subepithelial immune deposits, podocyte foot process effacement, and GBM expansion in a rat MN model. Moreover, the ROS-responsive CLT nanotherapy was associated with significantly lower toxicity to major organs than free CLT. These results suggest that encapsulating CLT into PPS-CPNs can improve efficacy and reduce toxicity as a promising treatment option for MN.
Source: openalex_inverted_index · Quality: baseline

Research context

PolymersNanomaterials

OpenAlex topics: Nanoparticle-Based Drug Delivery · Advanced Nanomaterials in Catalysis · Biomedical Research and Pathophysiology

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

National Engineering Technology Research Center for Miao Medicine, Guizhou Engineering Technology Research Center for Processing and Preparation of Traditional Chinese Medicine and Ethnic Medicine, College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, P. R. China

West China School of Pharmacy, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Sichuan University, Chengdu 610041, P. R. China

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P. R. China

UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, U.K.

Funding

Health Commission of Guizhou Province · Science and Technology Bureau, Guiyang Municipal Government · Guizhou Provincial Science and Technology Department · National Natural Science Foundation of China · Engineering Research Center of New Dosage Form and New Preparation of Traditional Chinese Medicine in Higher Education Institutions of Guizhou Province · Guizhou Province · National Engineering Technology Research Center for Traditional Chinese Medicine

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