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

Abstract

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.

Nephroprotective Effects of Selenium Nanoparticles Against Sodium Arsenite-Induced Damages

“…88 Recent studies related to nanotechnology have also focused on new approaches to either preserve mitochondrial functions or promote mitochondrial biogenesis to ameliorate nephrotoxicity induced by cisplatin exposure. 84,89 Our previous study has confirmed that Se supplementation in the form of nanomaterials effectively promoted mammalian mitochondrial functions. 90 In the present study, we also found that the mitochondria dysfunctions and the subsequent nephrotoxicity consequences of mitochondrial dysfunctions in the NaAsO 2 exposed mice renal tissues and HK2 cells were effectively ameliorated by the SeNPs supplementation.…”

“… 8 Mitochondria dysfunctions mediated nephrotoxicity has been heavily studied over past decades but continues to produce new and exciting findings. 84 Under pathological disorders, mitochondria dysfunctions triggered the damaged integrity of mitochondrial membrane potential (MMP), in turn, potentiating the release of a variety of mitochondrial components from the impaired mitochondrial into the cytoplasm or extracellular environment and promoting downstream oxidative stress, fibrosis, and inflammatory response cascades. 85 , 86 Moreover, the endonucleases from the mitochondria due to the hyperpermeable mitochondrial membranes translocate to the nuclei and cause DNA fragmentation.…”

Oxidative Damage as a Fundament of Systemic Toxicities Induced by Cisplatin—The Crucial Limitation or Potential Therapeutic Target?

“…The renal toxicity caused by cisplatin treatment can be successfully treated with polymeric and metallic nanoparticles that mostly act as inhibitors of oxidative stress and scavengers of generated free radicals. This could be found in the overview study by Davoudi et al [62]. Moreover, lately, synthesized ROS-responsive nanoparticles with "on demand" spatiotemporal release loaded with astaxanthin showed quite promising results in the treatment of oxidative stress during cisplatin-induced ototoxicity [63].…”

Natural killer cells strengthen antitumor activity of cisplatin by immunomodulation and ameliorate cisplatin-induced side effects

“…The most major side effect of cisplatin is nephrotoxicity since it is primarily excreted from the kidney. By causing oxidative stress, inflammation, mitochondrial malfunction, and apoptosis, cisplatin damages the kidneys [ 37 ]. We assessed the extent of kidney injury by measuring the expressions of the apoptosis-related proteins caspase-3 and BAX.…”