Table 1 The renoprotective mechanisms of different metallic and polymeric nanoparticles
Nanoparticles | Size (nm) | Zeta potential (mV) | Treatment | Renoprotective mechanisms | Ameliorative effects on kidneys | Refs. |
|---|---|---|---|---|---|---|
Metallic nanoparticles | ||||||
Cerium oxide nanoparticles (CONPs) | Less than 25 | – | Albino rats (60 mg/kg) (i.p.) | -As an anti-oxidant and anti-inflammatory agent | -Decreased: urea, creatinine, and histopathological damages -Increased: IL-10 and TAO | [52] |
Nanoceria | 113 | −15.4 | Swiss mice (0.2 and 2 mg/kg) (i.p.) | -Anti-oxidant and anti-inflammatory activities | -Decreased: urea, creatinine, lipid peroxidation, pro-inflammatory cytokines, and histopathological damages -Increased: catalase and GSH | [53] |
Green silver nanoparticles (CP-AgNPs) | 33.2 | – | Wistar rats (2.5 mg/kg) (i.p.) | -Inhibiting mitochondria-mediated apoptosis | - Decreased: Bax, caspase-3, and histopathological damages -Increased: Bcl-2 -Inhibited: the releases of AIF and cytochrome c from mitochondria | [54] |
N-(2-hydroxyphenyl) acetamide-conjugated gold nanoparticles (NA2-AuNPs) | 25–60 | −45.7 | Balb/c mice (Different doses) (i.p.) | -As a nano-carrier for a natural anti-oxidant | -Downregulated: NF-κB, iNOS and IL-6 -Upregulated: HO-1 | [55] |
Ficus carica L. leaves extract-loaded AuNPs | 100 | – | Albino rats (0.5 ml of Au NPs/Fig mixture as different v/v ratios) (orally) | -As a nano-carrier for a natural anti-oxidant | -Scavenging ROS -Mitigating AKI severity | [56] |
Selenium nanoparticles (SeNPs) | 45.9 | – | Pretreatment of albino rats with both SeNPs (0.5 mg/kg; orally) and fish oil before cisplatin administration and γ-radiation | -Inhibiting caspase-dependent apoptosis and inflammation -Strengthening the antioxidant system | -Decreased: urea, creatinine, TNF-α, caspase-3, cyclooxygenase-2, and histopathological damages | [57] |
Tea polyphenol (TP)-functionalized SeNPs (Se@TE) | Under microwave conditions: -After 0.5 h: 200.8 -After 1 h: 216.4 -After 2 h: 220.4 | -After 0.5 h: − 9.4 -After 1 h: − 11.5 -After 2 h: − 10.7 | -In vitro: HK-2 cells -In vivo: KM mice (1 and 2 mg/kg) (i.v.) | -As a nano-carrier for a natural anti-oxidant -Prevention of mitochondrial dysfunction -Activating seleno-enzymes | -Inhibited: dephosphorylation of AKT, phosphorylation of p38 MAPK, phosphorylation of JNK, phosphorylation of p53, proapoptotic genes (i.e., Bax and Bad), caspase-mediated apoptosis, and ROS production -Upregulated: anti-apoptotic genes (i.e., Bcl2 and Bcl-xL) | [58] |
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox) surface-functionalized SeNPs (Se@Trolox) | 100 | Lower than -50 | -In vitro: HK-2 cells | -Inhibiting apoptosis | -Blocked: ROS-induced p53 phosphorylation -Regulated: AKT/MAPK pathways | [59] |
Se@SiO2 nanocomposites | 53 | – | -In vitro: HK-2 cells -In vivo: pretreatment of C57BL/6 mice with Se@SiO2 (200 μl, 2 mg/ml) (i.v.) | -Reversing cisplatin-induced tubular damage | -Decreased: TNFα and IL-6 -Activated: Sirt1 at both in-vivo and in-vitro | [60] |
A. officinarum-silver nanoparticles (AG-AO) | 100 | – | Wistar rats (50 mg/kg/day or/and 100 mg/kg/day) (orally) | -As a nano-carrier for a natural anti-oxidant | -Decreased: ROS levels, Bax, p53, caspase3 and 9 proteins, TNFα, IL1β, NF-κB and NO pathways -Increased: Bcl2 protein, SOD, CAT and GSH -Inhibited: tubular atrophy, interstitial edema, necrosis and inflammation | [62] |
Polymeric nanoparticles | ||||||
Nanocurcumin (NC) | 240.7 | – | Sprague–Dawley rats (100 mg/kg/day) (orally) | -Changing the expression of cisplatin transporters on renal cells | -Increased: OCT2 | [66] |
Curcumin nanoparticles (CUR NPs) | 10–50 | – | Wistar albino rats (50 mg/kg body wt/day) (orally) | -Maintaining the mitochondrial function | -Decreased: lipid peroxidation, NO and TNF-α Increased: GSH and Na+/Ka + -ATPase activity | [73] |
The platinum complexes of curcumin (Pt-CUR@ mPEG-SS-PBAE-PLGA) | 154.87 | −20.8 | In vitro: HEK-293 cells In vivo: Balb/c nude mice (1 mg/kg of Pt-CUR) (tail intravenous injection) | -Redox and pH-dependent release | -Suppressed: ROS production | [74] |
Curcumin nanoparticles (CURNPs) | 2–100 | – | Rats (30 or 60 mg/kg b.w) (orally) | -As an antioxidant | -Decreased: urea, creatinine, F-2IsoPs, and histopathological damages -Increased: SOD and CAT activities | [72] |
SinaCurcumin® | – | – | Patients with localized muscle-invasive bladder cancer (180 mg/day) | -A complementary therapy | -No significant difference between nanocurcumin group and placebo group in response to grade 3/4 renal | [76] |
Cisplatin-incorporated liposome conjugated with EGFR antibodies (EGFR:lP-cDDP) | 247.9 | Balb/c nude mice (10 mg/kg) (i.v.) | -Targeted cisplatin delivery | -No pathological changes | [78] | |
Cisplatin-sodium alginate conjugate liposomes modified with EGF (CS-EGF-Lip) | 112.37 | −23.83 | Balb/c nude mice (i.v.) | -Targeted cisplatin delivery | -Decreased: urea and creatinine | [79] |
RNAi-Chemotherapy Layer by Layer Nanoparticle | 180 | −30 | Mice (i.v.) | -RNA-based therapeutics | -Increased: urea and creatinine at nanoparticles contained 16 mg/kg of cisplatin -Decreased: cisplatin-induced nephrotoxicity | [80] |
Lipoplatin | – | – | Patients with both cancer and renal failure | -Monotherapy -co-therapy with 5-fluorouracil-leucovorin or gemcitabine or paclitaxel | Creatinine at a normal level | [81] |
Lipocisplatin | 104.4 | – | Balb/c mice (6.5 mg Pt/kg) (tail intravenous injection) | -The size of cisplatin was more than cutoff for renal clearance | -Less drugs in kidneys | [82] |
Curcumin-loaded liposomes synthesized by microfluidic technology (Lipo-Cur) | 120 | – | Balb/c mice (20 mg/kg) (i.v. and orally) | – | -Decreased: urea, creatinine, and histopathological damages after a single dose | [83] |
Nanoparticulated honokiol | – | – | (ICR mice 5 mg/kg b.m) (Tail-vein injection) | -As a nano-carrier for a natural anti-oxidant -Inhibiting inflammation and fibrosis | -Inhibited: caspase-3-mediated apoptosis -Reversing acute kidney injury | [84] |
Lipid-coated cisplatin nanoparticles | 63.6 | + 12.8 | Xenograft mice | -Microneedle mediated delivery -pH-dependent release | -Decreased: urea, creatinine, and histopathological damages | [85] |
Cisplatin NanoComposite (CHIT/Cis/MgO NPs) | – | – | Wister rats (5.75 mg/kg b. wt.day) (i.p.) | -Sustained release | -Compared to cisplatin, it induced less malondialdehyde (MDA), 8-hydroxy-2’-deoxy-guanosine, NADPH oxidase, iNOS, NF-κB, STAT1, p53, caspase-3, phosphorylated mTOR, TNF-α and IL-1β -It decreased GSH, p-AMPK, p-PI3K, p-Akt less than cisplatin -Reduced: histopathological damages | [87] |
N-benzylN,O-succinyl chitosan (BSCT) | 356.6 | −16.7 | RPTEC/TERT1 cells | -Sustained and pH-dependent release | -Decreased: necrotic or late apoptotic cells | [88] |
CDDP complexed with γ-polyglutamic acid and chitosan (γ-PGA/CDDP-CS) | 196 | −59 | AB23G2-bearing mice (45 mg/kg) (i.p.) | -pH-dependent release | -Reduced: histopathological damages | [89] |
Poly (lactic-co-glycolic acid) nanoparticles | 284.8 | −15.8 | Balb/c mice (1.5 mg/kg of cisplatin in nanoparticles) (Tail-vein injection) | -A biphasic release profile | -Decreased: the cisplatin level, and CDDP-induced creatinine and urea nitrogen in kidneys | [96] |
PLGA-encapsulated nano-Boldine (NBol) | 115.5 | −17.4 | Swiss albino mice (Co-treatment of cisplatin with 10 mg/kg of NBol) (orally) | -As a nano-carrier for a natural anti-oxidant | -Recovery of SOD activity, creatinine and urea levels towards their normal ranges -Decreased: the rate of GSH depletion and the level of LPO -Normal glomerule -Negligible tubular damage | [97] |
N, N’-diphenyl-1, 4-phenylenediamine loaded PLGA nanoparticles (Nano-DPPD) | – | – | Sprague–Dawley rats (0.5 g/kg) (i.p.) | -Anti-fibrotic activity | -Inhibited: the interstitial fibrosis via decreasing CDDP-induced collagen contents in kidneys -Prevented: CDDP-induced macrophages infiltration -Decreased: tubular injury score, BUN, magnesium, creatinine, MCP-1 and hydroxyproline contents -Increased: creatinine clearance | [98] |
Thymoquinone nanoparticles (NP THY) | 210.9 | + 32.8 | Ehrlich solid carcinoma (ESC) mice model (3 mg/kg) (orally) | -Anti-oxidant and anti-inflammatory activities | -Decreased: TNF-α, IL-1β, NF-κB, urea, uric acid, creatinine, MDA and cystatin C -Increased: GSH, SOD and CAT -Preserved: parenchyma structure | [99] |
Micelles of poly(ethylene glycol)-b-poly(methacrylic acid) (cisplatin/cl-micelles) | 100–200 | −20 to −30 | C57Bl/6 mice (4 mg-cisplatin/kg b.w) (Tail-vein injection) | -Reducing renal exposure | -Recovery of creatinine and urea towards their normal ranges -No histopathological changes -No long-term effects | [101] |
Polymeric micelles (CDDP-PMs) (with drug/copolymer ratios of 1:3) | 18.39 | −4.77 | Balb/c nude mice (4 mg-cisplatin/kg) (Tail-vein injection) | -Tumor-targeting accumulation of cisplatin -A sustained, pH-dependent release | -Enhancing the dose of drug within systemic tolerability | [102] |
Micellar Pluronic F127-encapsulated quercetin | – | – | Wistar rats (Co-treatment of cisplatin and 100 mg/kg of P-quercetin containing 50 mg/kg quercetin)) (i.p.) | -As a nano-carrier for a natural anti-oxidant | -Decreased: CDDP-induced urea, creatinine, and tubular damage -Increased: creatinine clearance | [105] |
Chitosan derivatives, O-succinyl chitosan complexed with cisplatin | 317.67 | −19.23 | RPTEC/TERT1 cells | – | -Decreased: cytotoxic effects of cisplatin on renal proximal tubular cells | [107] |
Silymarin-loaded benzyl-functionalized succinyl chitosan (BSC) (SM-loaded PMs) | 326 | −23.8 | RPTEC/TERT1 cells | -pH-dependent release -As a nano-carrier for silymarin as a renoprotective agent | -low cytotoxicity on renal proximal tubular cells -Increased: permeability of silymarin across the intestinal membrane | [108] |
Human umbilical cord derived mesenchymal stem cells-exosomes | 103 | −24.15 | Pre-incubated rat renal tubular epithelial cells (NRK) with exosomes | -Inhibiting apoptosis | -Increased: CDDP-inhibited viability, proliferation and G1-phase cells -Decreased: cleaved caspase-9 and -3, Bim, Bad, and Bax, | [112] |
Carbon monoxide (CO)-loaded hemoglobin-vesicle (CO-HbV) | – | – | ICR mice (1000 mg Hb/kg) (Tail-vein injection) | -A renoprotectant | Suppressing caspase- 3-mediated apoptosis | [113] |
Gelatin microspheres incorporating cisplatin (GM-CDDP) | – | – | Balb/c mice (GM incorporating 40 mg CDDP) (i.p.) | -Allowed high-dose chemotherapy | -Decreased: the durability of the drug in the kidney | [114] |
Nanoparticles functionalized with folate (CP-FA-BSA-NPs) | 134.53 | −37.66 | Balb/c mice (5 mg/kg of CDDP in CP-FA-BSA-NPs) (Tail-vein injection) | -Targeted cisplatin delivery | -Decreased: CDDP-induced urea, creatinine, and histopathological damage | [128] |
PEG grafted-olyphosphazene–cisplatin conjugate (Polycisplatin) | 18.6 | ICR mice (5, 10, 15 and 20 mg platinum/kg) (i.v.) | -Passive targeting by EPR effect | -Decreased: CDDP-increased BUN, creatinine, and kidney weight/body | [116] | |
Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol 5 K) nanoparticles | Changed based on pH | – | Kunming mice (5 mg/kg of CDDP) (i.v.) | – | -Decreased: platinum concentration in kidney | [117] |
LHRH-modified dextran nanoparticles (Dex-SA-CDDP-LHRH) | – | – | Kunming mice (5 or 10 mg/kg of CDDP) (i.v.) | -Targeted cisplatin delivery | -Decreased: renal cisplatin accumulation | [118] |
Gallic acid-loaded Eudragit-RS 100 Nanoparticles (nano-gallic acid) | 180 | Positive charge | Wistar rats (10 mg/kg) (orally) | -Anti-oxidant and anti-inflammatory activities | -Decreased: MDA and ROS production in mitochondria, mitochondrial membrane damage, TNF-α, IL-6, and histopathological damage -Increased: GSH catalase, Superoxide dismutase, and Glutathione peroxidase in mitochondria | [119] |
Urolithin A nanoparticles | 214 | + 25.1 | C57BL/6 J mice (50 mg/kg) (orally) | -Reducing oxidative stress and apoptosis | -Attenuated: histopathological damages presented in CDDP-induced AKI -Decreased: mortality by 63%, oxidative stress, nuclear factor erythroid-2-related factor 2 (Nrf2) gene, and P53-inducible gene -Normalized: Poly(ADP-ribose) polymerase-1, miR-192-5p, miR-140-5p, intracellular NAD+, mitochondrial oxidative phosphorylation | [120] |
A magnetic CDDP-encapsulated nanocapsule (CDDP-PAA-NC) | 186 | – | Balb/c nude mice (10 mg/kg) (Tail-vein injection) | -A magnetic targeting | Decreased: BUN, creatinine, and histopathological damages | [121] |
Hyaluronan–cisplatin conjugate nanoparticles (HCNPs) entrapped in Eudragit S100-coated pectinate/alginate microbeads (PAMs) (HCNP-PAMs) | The diameters: 658 ± 73 µm | −20.16 for HCNPs | Wistar rats (3.5 mg/kg of cisplatin per Week) (orally) | -pH-dependent release | Decreased: creatinine level at day 29 | [122] |
Glutathione-scavenging poly(disulfide amide) nanoparticles (CP5) | 76.2 | Negative charge due to the presence of DSPE-PEG 3000 layer | A2780cis tumor bearing athymic nude mice | -Reversing CDDP resistance via GSH-scavenging process | Decreased: BUN | [123] |
Hyaluronic acid cisplatin/polystyrene-polymetformin (HA-CDDP/PMet) dual prodrug co-assembled nanoparticles | 166.5 | −17.4 | C57BL/6 mice (5 mg/kg of CDDP) (i.v.) | -Intracellular co-delivery with excellent cleavage | -Decreased: renal CDDP accumulation, BUN, creatinine, and histopathological damages | [124] |
EGFR-targeted albumin-cisplatin nanoparticles | 40 | – | Nude mice (3.0 mg/kg equivalent Pt Dose) (Tail-vein injection) | -Targeted cisplatin delivery -A sustained, pH-dependent release | Decreased: CDDP-induced cystic dilatation of renal tubes and tubular atrophy | [125] |
Pt (IV) prodrug-loaded ligand-induced self-assembled nanoparticles (GA-ALG@Pt NPs) | 141.9 | -36.7 | Balb/c nude mice bearing dual-xenograft and Healthy Kunming mice (5 mg/kg) (Tail-vein injection) or (25 mg/kg) (i.v.) | -Redox-sensitive -Targeted cisplatin delivery | Decreased: BUN, creatinine, and tubular damage | [126] |
Silk fibroin peptide/baicalein nanofibers (SFP/BA NFs): | – | – | In vitro: HK-2 cells In vivo: mice (50/100 mg/kg) (i.g.) | 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] |