Table 1:
Summary of recent nanoparticle formulations for kidney disease
| Indication | material | Morphology (nM) | cargo | Targeting Ligand (target) | Targeted cell type | result | Ref. |
|---|---|---|---|---|---|---|---|
| ADPKD | DSPE-PEG2k | Micelle (11–16) |
Rapamycin or salsalate | [KKEEE]3K (megalin) |
PTEC | NP combined with free metformin inhibited in-vitro cell proliferation and cyst growth | [1] |
| ADPKD | DSPE-PEG2k | Micelle (10–12) | Various mTOR inhibitors | CKDSPKSSKSIRFIPVST | CCD | Enhanced in-vitro antiproliferative effect | [2] |
| ADPKD | Chitosan-DSPE-PEG2k | Micelle (155) | Metformin | [KKEEE]3K (megalin) | PTEC | Reduced cystic % and kidney weight compared to free drug | [3] |
| DN | Gold (HAuCl4) | (157) | Gold | - | - | reduced in vitro ROS & apoptosis through SIRT3-SOD2 signaling | [4] |
| DN | Zinc oxide | Spherical (<50) | Zinc oxide | - | - | Slowed DN via interplay of autophagy and Nrf2/TXNIP/NLRP3 inflammasome signaling | [5] |
| GN | Lipid, DSPE-PEG | Spherical (114) |
Celastrol | VHPKQHRGGSKGC (VCAM-1) | GEC | Improved renal outcome, anti-inflammatory effect through eNOS increase, reduction of VCAM-1 expression. | [6] |
| TIN | Gold nanoparticles | Spherical (11–25) |
Gold nanoparticles | - | PTEC | Prevented tubule-interstitial injury, anti-inflammatory activity, reduced fibrosis, | [7] |
| Fibrosis | [2-(diisopropylamino) ethyl methacrylate] (PDPA)/PEG | Micelle (59) | Nitric oxide donor: (DNIC; [Fe2(μ-SEt)2(NO)4]) | pH-responsive polymer | Fibrotic kidney tissue | Suppressed myofibroblast activation and collagen I production | [8] |
| Fibrosis | Poly(lactic-co-glycolic acid) | Vesicle (70–80) |
Sorafenib | SLYQTDDRNDYI & RDYHPRDHTATW | Myo-fibroblast | Alleviates renal fibrosis | [9] |
| Fibrosis | Chitosan/GFP | Polyplex (150) |
Metformin | Chitosan (megalin) | RTEC | Improved anti-apoptotic, anti-inflammatory and anti-fibrotic effects | [10] |
| AKI | Gold | spherical (2–3) |
N-acetylcysteine | Passive [size] | Kidney | Reduced kidney ROS, inflammation, AKI and rodent mortality post rhabdomyolysis | [11] |
| AKI | Polyvinylpyrrolidone-curcumin | Micelles (5–8) | Curcumin and Zirconium-89 | Curcumin, size | Kidney | Reduced ROS, mitochondrial damage and AKI, PET-CT imaging | [12] |
| AKI | PEG-b-PAGA + (PDMAEMA-r-PAAPBA)-b-PPBAE | Spherical (141) | Curcumin | pH reactive size de-shelling and ROS reactive release | RTEC | Activated autophagy, reduced mitochondrial injury, ROS, ER (endoplasmic reticulum) stress, apoptosis, and AKI | [13] |
| AKI | D-α-tocopherol PEG1K succinate | Micelle (120 ) | Celastrol | Albumin coating | RTEC | Reduced systemic adverse effects while alleviating ischemia-reperfusion injury | [14] |
| AKI | Chitosan | Spherical (4.5) | Prussian blue | - | - | ROS reduction and reduced rodent mortality from AKI (rhabdomyolysis or cisplatin induced) | [15] |
| AKI | Solutol HS15 (12-hydroxystearic acid-PEG) | Micelle (13) | Myricetin | Size | Kidney | Reduced AKI, reduced ROS, inhibited cisplatin-induced activation of the DNA damage-cGAS−STING pathway. | [16] |
| AKI | Germanene | Nanosheet (0.8) |
Hydrogen | Passive | RTEC | Reduced ROS and AKI compared to NAC | [17] |
| AKI | PEGylated melanin | Spherical (25–40) | PJ34 (PARP-1 inhibitor) and melanin | Antibody (GPR97) | Injured RTEC | Reduced ROS, apoptosis, inflammation, activity of Keap-1/Nrf2/HO-1 & PARP-1/AIF pathways | [18] |
| AKI | Mn3O4 | Flower (110) | Mn3O4 | Passive | Kidney | Reduced ROS, cfDNA, apoptosis and AKI | [19] |
| AKI | Hyaluronic-acid, bilirubin | Micelle (85) | Prodrug of calcium ion chelator | Hyaluronic acid (CD44) | injured PTEC | Reduced ROS, intra cellular calcium, ER stress, apoptosis pathways, TNFα and AKI | [20] |
| AKI | PEG methyl ether-bl-poly(lactide-co-glycolide) | Spherical (442) | Formoterol (long acting β2 agonist) | Passive | PTEC | Kidney expression and reduced myocardial expression of mitochondrial biogenesis | [21] |
| AKI | Gallic acid-gallium polyvinyl pyrrolidone | spherical (25) |
Gallium | - | - | Reduced intracellular free iron, mitochondrial damage, and AKI, inhibited cisplatin induced ferroptosis in vitro | [22] |
| AKI | Phenylene-cyclam, hexa-methylene-bi-sacryl-amide | Spherical polyplex (127) |
p53 siRNA, CXCR4a | Poly[amido amine] CXCR4 antagonist (CXCR) | RTEC | Reduced p53 mRNA and AKI | [23] |
| Indication | Material | Morphology (nM) | Cargo | Targeting Ligand (target) | Targeted cell type | result | Ref. |
| AKI | Chitosan modified with α-cyclam-ptoluic acid | Polyplex (129) |
p53 siRNA, α-cyclam-ptoluic acid (CXCR4a) | α-cyclam-ptoluic acid (CXCR4) | Injured RTEC | Reduced p53 transcription, apoptosis, macrophage and neutrophil infiltration, and AKI | [24] |
| AKI | Polyethyleneimine | Polymer | CXCR4 antagonist | Poly hydroxyl | RTEC | Increased uptake to IRI kidney | [25] |
| AKI | M13 DNA strands | rDON | IL-33 cytokine | Passive [size] | Kidney | Increased kidney Tregs and recovery from IRI, macrophages shifted from M1 to M2 | [26] |
| AKI detection | Aza-boron-dipyrromethene | Brush shaped polyplex (4) | aza-boron-dipyrromethene (aza-BODIPY) |
cRGD | Kidney | Renal-cleared probe for non-invasive diagnosis of renal IRI, with 10x brightness then previous study | [27] |
| AKI detection | Activatable small molecule | Small molecule | NIR-II probe | (Externalized phosphatidylserine and activate caspase) | Apoptotic cells | Detected AKI 24h post IV cisplatin, while Cr and BUN were not yet significantly elevated | [28] |
| AKI | M13mp18 DNA | rDON | Gold Nanorods |
Passive [size] (NIR-II triggered by miR21 upregulation) |
Kidney | Allowed detection of AKI 10 minutes after IRI and increased ROS scavenger function instantaneously | [29] |
| IRI | M13 DNA | rDON (2*60*90) | Anti C5a aptamers | Passive [size] | Kidney | Reduced renal and systemic complement inflammation, ROS and AKI 24h post IRI | [30] |
| ACR | N Polystyrene | Spherical (500) | Isothiocyanate | (MARCO) | inflammatory monocytes | Reduced ACR and mortality compared to no-immunosuppression | [31] |
| RCC | Poly-L-lysine hydrobromide | Spherical (3–4) | yitrium (90Y) | L-Serine residues (KIM1) | Injured RTEC | Reduced kidney tumor growth, reduced nephrotoxicity | [32] |
| RCC | DSPE-PEG2k | Micelle (14) | HIF2α siRNA | peptide derived from CD27 (CD70) | Clear cell RCC | ~70% gene knockdown of HIF2 and its downstream genes | [33] |
| DNA/RNA delivery | Polyethyleneimine, sorbitol | polyplex (69–228) |
Plasmid DNA | Chitobionic acid (Vimentin) | PTEC | Enhanced transfection efficiency | [34] |
ACR – Acute cellular rejection, AIF - apoptosis-inducing factor, CCD – Cortical collecting duct, CD - Cluster of differentiation, cGAS - Cyclic GMP–AMP synthase, DN – Diabetic nephropathy, DSPE - 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine, eNOS - Endothelial NO synthase, GEC – Glomerular endothelial cells, GFP – Green fluorescent protein, HIF - Hypoxia-inducible factor, KEAP1 - Kelch-like ECH-associated protein 1, KIM1 - Kidney Injury Molecule-1, MΦ - inflammatory monocytes, mTOR- Mammalian target of rapamycin, NLRP3 - nod, LRR and pyrin domain-containing protein 3, NRF2 - nuclear factor erythroid 2–related factor 2, PAAPBA- poly2-(acrylamido)phenylboronic acid, PAGA- poly N-acryloyl glucosamine, PARP-1 - Poly [ADP-ribose] polymerase 1, PDPA - poly(2-(diisopropylamino)ethyl methacrylate, PDMAEMA- poly-2-(dimethylamino)ethyl methacrylate, PEG – Polyethylene glycol, PPBAE- poly(beta-amino esters), rDON - Rectangular DNA origami nanocarriers, SOD2 - superoxide dismutase 2, STING - stimulator of interferon genes, TNFα - Tumor necrosis factor α, Treg – regulatory T cell, TXNIP - thioredoxin-interacting protein, VCAM-1 - Vascular cell adhesion protein 1