Current Strategies and Potential Prospects for Nanoparticle-Mediated Treatment of Diabetic Nephropathy

Abstract

Diabetic nephropathy (DN), a severe microvascular complication of diabetes mellitus (DM), is the most common form of chronic kidney disease (CKD) and a leading cause of renal failure in end-stage renal disease. No currently available treatment can achieve complete cure. Traditional treatments have many limitations, such as painful subcutaneous insulin injections, nephrotoxicity and hepatotoxicity with oral medication, and poor patient compliance with continual medication intake. Given the known drawbacks, recent research has suggested that nanoparticle-based drug delivery platforms as therapeutics may provide a promising strategy for treating debilitating diseases such as DN in the future. This administration method provides multiple advantages, such as delivering the loaded drug to the precise target of action and enabling early prevention of CKD progression. This article discusses the development of the main currently used nanoplatforms, such as liposomes, polymeric NPs, and inorganic NPs, as well as the prospects and drawbacks of nanoplatform application in the treatment of CKD.

Keywords:

• diabetic nephropathy
• DN
• nanoplatform
• route of administration

Abbreviations

DN, Diabetic nephropathy; CKD, chronic kidney disease; DM, diabetes mellitus; T1DM, type 1 DM; T2DM, type 2 DM; ECM, extracellular matrix; LNs, lipid nanoparticles; NPs, nanoparticles; STZ-NA, streptozotocin-nicotinamide; PCL-PEI, polycaprolactone-polyethyleneimine; KTP, kidney-targeting peptide; RH, rhein; KLPPR, kidney-targeted RH-loaded liponanoparticles with a yolk-shell structure composed by PCL-PEI-based cores and KTP-modified lipid layers; SLN, Solid lipid nanoparticle; MET, metformin; PEG, Polyethylene glycol; CS, chitosan; FBG, fasting blood glucose; ChnPs, CS NPs; PLGA, poly lactic-co-glycolic acid; ChAuNP/PLGACS gold NPs functionalized with PLGA; POL-NPs, polydatinloaded CS NPs; BBR, Berberine; BC, Brij-grafted-CS; BC12, BC with 12% grafting; Pgp, P-glycoprotein; Brij-S20, Polyethylene glycol octadecyl ether; PLA, poly D, L-lactide; PLA-P85-PLA, PLA segments to both ends of a Pluronic P85 copolymer to generate an amphiphilic vesicles; TC, Tinospora cordifolia; TC-PLA NPs, TC-PLA nanoparticles; MNPs, magnetic nanoparticles; USPIO-PEG NPs, ultrasmall superparamagnetic iron oxide PEG-coated NPs; C- Mn₃O₄NPs, citrate func-tionalized Mn₃O₄ nanoparticles; ROS, reactive oxygen species; ZnO NPs, Zinc oxide NPs; RAGE, receptor of advanced glycation end-products; HMSN, hollow mesoporous silica nanocomposite; AuNPs, Gold NPs; EMT, epithelial-mesenchymal transition; QDs, quantum dots; AR, Aldose reductase; TLR4, Toll-like receptor 4; CCG, cinaciguat; SGc, soluble form of guanylate cyclase; GTP, guanosine triphosphate; cGMP, cyclic guanosine monophosphate; PVP, Polyvinyl pyrrolidone; PVA, Polyvinyl alcohol; AgNPs@PVP, PVP-coated silver nanoparticles; AgNPs@PVA, PVA-coated silver nanoparticles; PPE-AuNP, peel extract–stabilized gold nanoparticle.

Acknowledgments

Previously reported data were used to support this study and are available at DOI. These prior studies (and datasets) are cited at relevant places within the text as references.

Disclosure

The authors declare that they have no conflicts of interest.

Additional information

Funding

This study was financially supported by the Science and Technology Development Plan Projects of Jilin Province (Grant No. 20210101294JC and Grant No.20220204032YY).