Nano-Formulations of Natural Antioxidants for the Treatment of Liver Cancer
Abstract
:1. Introduction
2. Nano-Formulations Containing (Poly)phenolic Antioxidants
3. Nano-Formulations Containing Terpenoid Antioxidants
4. Nano-Formulations Containing Supplemental Antioxidants
5. Challenges and Future Perspectives
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Nano-Formulation | API | Excipients | Physical Characteristics | Biological Activity | Ref. |
---|---|---|---|---|---|
FA-HSA-RES-NPs | Resveratrol | Folic acid, human serum albumin | Spherical shape (~102 nm), high EE (~98%), and DL (~15%) | Enhanced cell uptake and antiproliferative activity in vitro and improved biodistribution | [64] |
GA-HSA-RES-NPs | Resveratrol | Glycyrrhizic acid, human serum albumin | Nearly spherical (~108 nm), high EE (83.6%), and DL (11.5%) | Enhanced antiproliferative activity in HepG2 cells and better biodistribution via EPR effect and ASGPR-mediated endocytosis | [65] |
RES-AuNPs | Resveratrol | Gold nanoparticles | Spherical shape (~39–1110 nm) and zeta potential (ζ) = −32.5 mV | Stronger apoptosis induction via downregulation of pro-caspase-9, pro-caspase-8, PI3K, and Akt and upregulation of caspase-8 and Bax, tumor growth suppression. | [70] |
CUR-GCS@NPs | Curcumin | PLGA-PEG, galactosylated chitosan | Particle size ~100 nm, EE = ~94%, DL = 4.56%, ζ = −9.82 mV, Polydispersity index (PDI) = 0.25 | Targeted delivery to liver tumor tissues, enhanced biocompatibility | [79] |
APO-GCS@NPs | Apocynin | PEG-PLGA, galactosylated chitosan | Particle size 224–232 nm, EE = 34%, pH-dependent drug release (31–60% after 72 h) | Significant improvement of antiproliferative activity against HepG2 cells | [83] |
CUR-G-BSA-NPs | Curcumin | bovine serum albumin, galactosyl units | Spherical shape (~116 nm), high drug release rate | Better antiproliferative activity against HepG2 cells (~5,6-fold compared to the free drug) | [86] |
Dox/CUR-NPs | Doxorubicin, Curcumin | Glyceril distearate, soybean lecithin, Polyoxyl 40 Hydrogenated Castor Oil, glycerin, triglycerides medium chain | Spherical shape (~89 nm), high EE (Dox = 97.1% and CUR = 99.8%), ζ = −14.3 mV, PDI = 0.22, sustained release profile (Dox = 55% and CUR = 40% after 48 h) | Synergistic antiproliferative effects in HCC models, modulation on apoptosis, proliferation-, angiogenesis-, MDR- and hypoxia-related mRNAs and proteins | [88] |
FA-CA@AgNPs | Folic acid, Caffeic Acid | Silver nanoparticles | Small particle size (10–20 nm) | Higher antiproliferative effects, apoptosis induction by caspase-8, caspase-3, and TNF-α pathways | [90] |
Q-AuNPs | Quercetin | Gold nanoparticles | Spherical shape (~114 nm) | Higher cellular uptake and apoptosis induction via the p53-ROS pathway | [94] |
RU-PLGA-NPs | Rutin | PLGA | Particle size ~211 nm, high EE (77.83%) and DL (6.39%), sustained release (71% after 48 h) | Overexpression of GPx, GTS, MPO, CAT, and SOD, downregulation of IL-1β, IL-6, TNF-α, and NF-κB, and improvement of membrane-bound enzyme activity (Ca2+-ATPase, Na+/K+-ATPase, and Mg2+-ATPase) | [97] |
HP-mPEG5000-S-AuNPs | Hesperetin | mPEG5000-SH, gold nanoparticles | Spherical, triangular, and pentagon in shape (110–120 nm), ζ = −4.38 mV, sustained release (80% after 72 h) | High antioxidant activity, improved hepatic parameters in HCC models, inhibition of inflammatory markers, antioxidant enzymes, and ATPase activity related to liver damage | [98]. |
CE-HK-NPs | Honokiol | Chitin, epigallocatechin-3- gallate | Spherical shape (~80 nm), sustained release (80% after 24 h) | Extended antiproliferative activity in vitro and reduction of tumor growth (~84%) after inter-tumoral injection (3x week) | [101] |
UFG-PLGA-NPs | Umbelliferone β-d-galactopyranoside | PLGA | Uniform size distribution (~187 nm), EE = 60–90%, sustained in vitro DR (82.5% after 48 h) | Reduced liver/body weight ratio and liver nodules in DEN-treated rats, inhibition of HCC cell proliferation in vitro. | [103] |
AG-PLGA-NPs | Andrographolide | PLGA | Particle size ~66 nm, EE = 64% | Decreased serum levels of ALT, AST, and ALP, arsenic deposition in the liver, SOD, CAT, and GSH | [111] |
CDDP/OA-LCC@NPs | Oleanolic Acid, Cisplatin | Mono-methoxy polyethylene glycol 2000-distearoyl phosphatidylethanolamine (PEG-DSPE 2000) 1,2-dioleoyl-in-glycerol-3-phosphate (DOPA), dehydrogenated soya phosphatidylcholine (HSPC), Calcium carbonate | Particle size ~206 nm, EE = ~64%, pH-dependent drug release (70% of CDDP at pH = 5.5 and 28% of CDDP at pH = 7.4) | Induction of apoptosis via downregulation of P13K/Akt/mTOR pathway and upregulation of p53 proapoptotic pathway, inhibition of drug resistance by downregulating proteins like XIAP and Bcl-2 via the NK-κB pathway | [116] |
OA-PLGA-TPGS-NPs | Oleanolic Acid | PLGA, d-α-tocopheryl PEG1000 succinate | Spherical shape (~200 nm), DL = ~28%, EE = ~92% | Increased in vitro cytotoxicity against HepG2 cells compared to the free drug, and higher growth inhibition rate in volume | [117] |
PLT/TYR-CSL@NPs | Parthenolide, Tyrosol | Chitosan, Lecithin | Particle size ~38 nm; PLT EE = 93% | Cancer-selective cytotoxicity in vitro assessed on HepG2 cells and potent antioxidant activity. Apoptotic effects by upregulating the expression of the apoptotic genes Bax and caspase-8 and downregulating the expression of the anti-apoptotic gene Bcl-2 | [121] |
Vit. E/C@SeNPs | Vitamin C, Vitamin E | Selenium nanoparticles | Particle size ~50 nm, high antioxidant capacity (~76% DPPH scavenging), improved liver function markers | Higher antioxidant capacity (~76% DPPH scavenging), improved ALT, AST, ALP, total bilirubin, and GGT, increased GSH concentration and CAT activity | [125] |
Precirol® ATO5 | α-Tocotrienol | Precirol ATO5 Glyceryl distearate, miglyol, poloxamer 407 | Particle size ~78 nm, ζ = −11 mV, PDI = 0.24 | Increased cytotoxicity in vitro (IC50 = 15 µM compared to IC50 = 10 µM of the free drug), decreased expression of the anti-apoptotic genes survivin and Bcl-2, and increased expression of the proapoptotic genes Bid and Bax | [128] |
CoQ10-CS/HA@NPs | Coenzyme Q10 | Hyaluronic acid, Chitosan | Monodispersed, average diameter ~54 nm | Hepatoprotective effects against OS and xenobiotics, enhanced cellular antioxidant capacity | [131] |
DHA-LDL-NPs | Docosahexaenoic acid | LDL | Particle size ~20 nm | Selective cytotoxicity against liver cancer cells, modulation of oxidative stress and mitochondrial damage | [138] |
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Cristani, M.; Citarella, A.; Carnamucio, F.; Micale, N. Nano-Formulations of Natural Antioxidants for the Treatment of Liver Cancer. Biomolecules 2024, 14, 1031. https://doi.org/10.3390/biom14081031
Cristani M, Citarella A, Carnamucio F, Micale N. Nano-Formulations of Natural Antioxidants for the Treatment of Liver Cancer. Biomolecules. 2024; 14(8):1031. https://doi.org/10.3390/biom14081031
Chicago/Turabian StyleCristani, Mariateresa, Andrea Citarella, Federica Carnamucio, and Nicola Micale. 2024. "Nano-Formulations of Natural Antioxidants for the Treatment of Liver Cancer" Biomolecules 14, no. 8: 1031. https://doi.org/10.3390/biom14081031