Targeting strategies for drug delivery to the kidney: From renal glomeruli to tubules

Liu, Chunping; Hu, You; Lin, Johnson; Fu, Hualin; Lim, Lee Yong; Yuan, Zhixiang

doi:10.1002/med.21532

Cited by 66 publications

(46 citation statements)

References 128 publications

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“…Major methods of targeting proximal renal tubular cells are the use of protein- or peptide-based carriers and the use of nanoparticles (Liu et al, 2019). Protein- or peptide-based carriers consist of a low molecular weight protein (LMWP; e.g., lysozyme and immunoglobulins) to which the drug is linked (Zhou et al, 2014).…”

Section: Targeted Therapymentioning

confidence: 99%

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools

et al. 2019

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Chronic kidney disease (CKD) is an increasing health burden (affecting approximately 13.4% of the population). Currently, no curative treatment options are available and treatment is focused on limiting the disease progression. The accumulation of senescent cells has been implicated in the development of kidney fibrosis by limiting tissue rejuvenation and through the secretion of pro-fibrotic and pro-inflammatory mediators termed as the senescence-associated secretory phenotype. The clearance of senescent cells in aging models results in improved kidney function, which shows promise for the options of targeting senescent cells in CKD. There are several approaches for the development of “senotherapies”, the most rigorous of which is the elimination of senescent cells by the so-called senolytic drugs either newly developed or repurposed for off-target effects in terms of selectively inducing apoptosis in senescent cells. Several chemotherapeutics and checkpoint inhibitors currently used in daily oncological practice show senolytic properties. However, the applicability of such senolytic compounds for the treatment of renal diseases has hardly been investigated. A serious concern is that systemic side effects will limit the use of senolytics for kidney fibrosis. Specifically targeting senescent cells and/or targeted drug delivery to the kidney might circumvent these side effects. In this review, we discuss the connection between CKD and senescence, the pharmacological options for targeting senescent cells, and the means to specifically target the kidney.

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Section: Targeted Therapymentioning

confidence: 99%

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools

et al. 2019

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“…Besides ex vivo applications, developments in targeted delivery methods bring gene therapy in NPH patients one step closer ( Liu et al, 2019 ). Whereas adeno-associated virus (AAV)-vector delivery of wildtype gene and CRISPR/Cas9 to retinal cells via subretinal injection has been demonstrated in Bbs4 and Cep290 mouse models, respectively, delivery of viral vector to the kidney via systemic injection is limited because AAV particles do not pass the glomerular filtration barrier ( Simons et al, 2011 ; Ruan et al, 2017 ; Rubin et al, 2019 ).…”

Section: Developments and Future Directionsmentioning

confidence: 99%

Renal Ciliopathies: Sorting Out Therapeutic Approaches for Nephronophthisis

Stokman

Saunier

Benmerah

2021

Front. Cell Dev. Biol.

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Nephronophthisis (NPH) is an autosomal recessive ciliopathy and a major cause of end-stage renal disease in children. The main forms, juvenile and adult NPH, are characterized by tubulointerstitial fibrosis whereas the infantile form is more severe and characterized by cysts. NPH is caused by mutations in over 20 different genes, most of which encode components of the primary cilium, an organelle in which important cellular signaling pathways converge. Ciliary signal transduction plays a critical role in kidney development and tissue homeostasis, and disruption of ciliary signaling has been associated with cyst formation, epithelial cell dedifferentiation and kidney function decline. Drugs have been identified that target specific signaling pathways (for example cAMP/PKA, Hedgehog, and mTOR pathways) and rescue NPH phenotypes in in vitro and/or in vivo models. Despite identification of numerous candidate drugs in rodent models, there has been a lack of clinical trials and there is currently no therapy that halts disease progression in NPH patients. This review covers the most important findings of therapeutic approaches in NPH model systems to date, including hypothesis-driven therapies and untargeted drug screens, approached from the pathophysiology of NPH. Importantly, most animal models used in these studies represent the cystic infantile form of NPH, which is less prevalent than the juvenile form. It appears therefore important to develop new models relevant for juvenile/adult NPH. Alternative non-orthologous animal models and developments in patient-based in vitro model systems are discussed, as well as future directions in personalized therapy for NPH.

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“…Over recent years, nanomaterials have achieved research success in the diagnosis and treatment of renal diseases [58]. There has been a rapid growth in the nanotechnologies used in the application of drug delivery systems for the pharmaceutical treatment of AKI [59]. Additionally, there is a significant potential for the application of these novel nanomaterials in molecular imaging systems to promote the early detection of AKI [41].…”

Section: The Role Of Nanomaterials In Acute Kidney Injurymentioning

confidence: 99%

Recent advances in engineered nanomaterials for acute kidney injury theranostics

Wang

Zhang

et al. 2020

Nano Res.

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Acute kidney injury (AKI), has become the focus of increasing attention due to its high risk of death. The early diagnosis and treatment of AKI significantly reduce the risk of renal tissue damage and kidney dysfunction. However, the efficient early diagnosis and treatment approach for AKI remains a challenge. AKI screening via precise nanomaterial theranostics is a new alternative approach. This study summarizes the recent advances in functional nanomaterials in the early detection and treatment of AKI. The challenges and problems in the use of nanomaterials for AKI in clinical applications are also discussed. It is anticipated that highlighting these new advances will lay the foundation for further translational research on the promising application of nanomaterials for AKI.

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Targeting strategies for drug delivery to the kidney: From renal glomeruli to tubules

Cited by 66 publications

References 128 publications

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools

Renal Ciliopathies: Sorting Out Therapeutic Approaches for Nephronophthisis

Recent advances in engineered nanomaterials for acute kidney injury theranostics

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