Prevention of cisplatin-induced nephrotoxicity by kidney-targeted siRNA delivery

Aydin, Erkin; Cebeci, Aysun; Lekesizcan, Ayça

doi:10.1016/j.ijpharm.2022.122268

Cited by 6 publications

(5 citation statements)

References 52 publications

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“…In the scope of these facts about CP, there is a drastic need to investigate new preventive safe and effective renoprotective drugs. [34]. "Cr.Cl is the volume of blood plasma cleared of creatinine per unit time.…”

Section: Discussionmentioning

confidence: 99%

The Renoprotective Effects of Liraglutide and Alfacalcidol against Cisplatin Induced Nephrotoxicity in Mice

Fehil,

Yassin,

Mahmoud

et al. 2024

JAMMR

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Cisplatin (CP) is an important platinum-based chemotherapy agent widely used to treat solid tumors. However, nephrotoxicity is the main limiting adverse effect in 25%–35% of patients treated with even a single dose of CP. This study aimed to evaluate the role of liraglutide (LIRA) and alfacalcidol (ALFA), each of them alone and in combination, in prevention of CP-induced nephrotoxicity. Forty male albino mice were divided into five groups including normal control group and groups CP, CP with LIRA, CP with ALFA, or CP with LIRA and ALFA. Nephrotoxicity was induced by single intraperitoneal injection of CP in a dose 12mg/kg. LIRA and/or ALFA treatment was started 5 days before induction of nephrotoxicity and continued till the end of experiment. Kidney function tests, oxidative stress and ferroptosis parameters were assessed. Histopathological and immunohistochemical examination were performed on kidney tissues. Both LIRA and ALFA monotherapy resulted in a significant improvement in kidney function tests, increased antioxidant levels, inhibition of ferroptosis and improved histopathological findings. LIRA showed more improvement compared to ALFA and their combination showed better results than each one alone. In conclusion, LIRA and ALFA either alone or in combination, represent a promising preventive modality for amelioration of CP-induced nephrotoxicity.

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Section: Discussionmentioning

confidence: 99%

The Renoprotective Effects of Liraglutide and Alfacalcidol against Cisplatin Induced Nephrotoxicity in Mice

Fehil,

Yassin,

Mahmoud

et al. 2024

JAMMR

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“… 98 There have since been three different publications demonstrating therapeutic siRNA-loaded MNP formulation and kidney delivery: siRNA targeting the inflammatory cytokine IL-1 β , 100 the CD8 T-cell regulating programmed death-ligand 1, 111 and simultaneous delivery of an siRNA cocktail against organic cation transporters—1 and 2, p53, protein kinase δ , and γ -glutamyl transpeptidase. 112 It is exciting that, in all cases, kidney-specific knockdown of the siRNA target was demonstrated, in one case up to 3 weeks after a single dose, with no knockdown in other organs observed. 111 In addition, loading of mRNA into MNPs and expression of a reporter protein (mCherry) in renal tubular cells in vitro has been reported.…”

Section: Polymeric Mesoscale Nps—tubular Kidney Targeting At the Meso...mentioning

confidence: 99%

“… 98 , 102 , 103 , 108 Cisplatin-induced models of AKI are also commonly used in the field, with successful demonstration of both an siRNA cocktail and small molecule edaravone delivery. 100 , 112 Although the siRNA cocktail delivery and triptolide delivery studies were administered daily for 3 days, the other AKI studies described here were single administrations associated with model initiation or up to 24 hours after.…”

Section: Polymeric Mesoscale Nps—tubular Kidney Targeting At the Meso...mentioning

confidence: 99%

Targeting the Kidneys at the Nanoscale: Nanotechnology in Nephrology

Vasylaki,

Ghosh,

Jaimes

et al. 2024

Kidney360

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Kidney diseases, both acute and chronic, are a substantial burden on individual and public health and they continue to increase in frequency. Despite this and an intense focus on the study of disease mechanisms, few new therapeutic approaches have extended to the clinic. This is in part due to poor pharmacology of many, if not most, therapeutics with respect to the sites of kidney disease within the glomerulus or nephron. Considering this, within the past decade, and more pointedly over the past two years, there have been substantial developments in nanoparticle systems to deliver therapeutics to the sites of kidney disease. Here, we provide a broad overview of the various classes of nanomaterials that have been developed to improve therapeutic development for kidney diseases, the strategy used to provide kidney accumulation, and briefly the disease models they focused on, if any. We then focus on one specific system, polymeric mesoscale nanoparticles, which has broadly been used over 13 publications, demonstrating targeting of the tubular epithelium with 26-fold specificity compared to other organs. While there have been several nanomedicines that have advanced to the clinic in the past several decades, including mRNA-based COVID vaccines and others, none have focused on kidney diseases specifically. In total, we are confident that the rapid advancement of nanoscale-based kidney targeting and a concerted focus by clinicians, scientists, engineers, and other stakeholders will push one or more of these technologies into clinical trials over the next decade.

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“…Besides, a study used chitosan/siRNA nanoparticles to passively target kidneys. These nanoparticles altered CDDP-induced apoptotic proteins, e.g., p53, protein kinase C-δ (PKCδ) and GGT, by gene therapy to protect kidneys against CDDP-induced proximal tubule damages [ 92 ].…”

Section: Polymeric Nano-formulationsmentioning

confidence: 99%

“… Improved anti-oxidant responses Decreased: DNA damage, cGAS-STING pathway activation, creatinine, and BUN Increased: SOD [ 127 ] CaCO3 nanoparticle (CDDP/OA-LCC NPs) 217 −23.7 Balb/c nude mice (i.v.) -A sustained, pH-dependent release -Anti-inflammatory activities Decreased: NF-κB activation [ 115 ] Chitosan/siRNA nanoparticles – – – Passively target kidneys by gene therapy to protect them against apoptosis Decreased: OCT1&2, p53, PKCδ and γGT proteins, and creatinine, and BUN [ 92 ] …”

Section: Introductionmentioning

confidence: 99%

Ameliorative impacts of polymeric and metallic nanoparticles on cisplatin-induced nephrotoxicity: a 2011–2022 review

et al. 2022

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Cisplatin (CDDP) is a well-known platinum-based drug used in the treatment of various malignancies. However, the widespread side effects that this drug leaves on normal tissues make its use limited. Since cisplatin is mainly eliminated from the kidneys, CDDP-induced nephrotoxicity is the most significant dose-limiting complication attributed to cisplatin, which often leads to dose withdrawal. Considering the high efficiency of cisplatin in chemotherapy, finding renoprotective drug delivery systems for this drug is a necessity. In this regard, we can take advantages of different nanoparticle-based approaches to deliver cisplatin into tumors either using passive targeting or using specific receptors. In an effort to find more effective cisplatin-based nano-drugs with less nephrotoxic effect, the current 2011–2022 review study was conducted to investigate some of the nanotechnology-based methods that have successfully been able to mitigate CDDP-induced nephrotoxicity. Accordingly, although cisplatin can cause renal failures through inducing mitochondria dysfunction, oxidative stress, lipid peroxidation and endoplasmic reticulum stress, some CDDP-based nano-carriers have been able to reverse a wide range of these advert effects. Based on the obtained results, it was found that the use of different metallic and polymeric nanoparticles can help renal cells to strengthen their antioxidant systems and stay alive through reducing CDDP-induced ROS generation, inhibiting apoptosis-related pathways and maintaining the integrity of the mitochondrial membrane. For example, nanocurcumin could inhibit oxidative stress and acting as a ROS scavenger. CONPs could reduce lipid peroxidation and pro-inflammatory cytokines. CDDP-loaded silver nanoparticles (AgNPs) could inhibit mitochondria-mediated apoptosis. In addition, tea polyphenol-functionalized SeNPs (Se@TE) NPs could mitigate the increased level of dephosphorylated AKT, phosphorylated p38 MAPK and phosphorylated c-Jun N-terminal kinase (JNK) induced by cisplatin. Moreover, exosomes mitigated cisplatin-induced renal damage through inhibiting Bcl2 and increasing Bim, Bid, Bax, cleaved caspase-9, and cleaved caspase-3. Hence, nanoparticle-based techniques are promising drug delivery systems for cisplatin so that some of them, such as lipoplatins and nanocurcumins, have even reached phases 1–3 trials.

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Prevention of cisplatin-induced nephrotoxicity by kidney-targeted siRNA delivery

Cited by 6 publications

References 52 publications

The Renoprotective Effects of Liraglutide and Alfacalcidol against Cisplatin Induced Nephrotoxicity in Mice

The Renoprotective Effects of Liraglutide and Alfacalcidol against Cisplatin Induced Nephrotoxicity in Mice

Targeting the Kidneys at the Nanoscale: Nanotechnology in Nephrology

Ameliorative impacts of polymeric and metallic nanoparticles on cisplatin-induced nephrotoxicity: a 2011–2022 review

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