Recent Advances in Nanotechnology with Nano-Phytochemicals: Molecular Mechanisms and Clinical Implications in Cancer Progression
Abstract
:1. Introduction
2. Research Milestones in Nanotechnology and Anticancer Nanodrugs
3. Recent Advances in Nanotechnology Targeting Cancer Progression
3.1. Carbon-Based NPs
3.2. Ceramic NPs
3.3. Metal NPs
3.4. Quantum Dots
3.5. Magnetic NPs
3.6. Polymeric NPs
3.7. Lipid-Based NPs
3.8. Dendrimers
3.9. The Enhanced Permeability and Retention Effect
3.10. The Reticuloendothelial System Barrier in Nanoparticle Drug Delivery
4. Molecular Mechanisms of Nano-Phytochemicals in Cancer Progression
4.1. Anacardic Acid
4.2. Betulinic Acid
4.3. Curcumin
4.4. EGCG
4.5. Ferulic Acid
4.6. Gambogic Acid
4.7. Ginsenosides
4.8. Kaempferol
4.9. Lycopene
4.10. Resveratrol
5. Clinical Implications
6. Conclusions and Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Botanical Name | Natural Compound | Structure | Type of Nanoparticles | Efficacy | Mechanism | Concentration | Cancer | Cell Line | References |
---|---|---|---|---|---|---|---|---|---|
Anacardium occidentale | Anacardic acid | Protein (Docetaxel-loaded AA-GEM-BSA) | Apoptosis↑ Tumor size↓ | HSP90, Hsp70, GRP78, Hsp70, CDK-4, MMP-9, Bcl-2, and Mcl-1↓ | AA-GEM-BSA NP: 10, 15, 20 ug/mL; BSA NP: 10, 15, 20 ug/mL; In vivo: 0.5 mg/mL | Breast cancer in vivo | MCF-7, MDA-MB-231 DMBA induced breast cancer model | [125] | |
Betula pubescens | Betulinic acid | Polymer (PLGA-mPEG) | Apoptosis↑ ROS↑ tumor volume↓ | ROS↑ | GEM NP: 17.59 ± 2.91 ng/mL GEM+BA NP: 7.62 ± 0.84 ng/mL 2~8.5 mg/kg | Pancreatic cancer in vivo | Panc1 Ehrlich tumor model | [128] | |
Polymer (B-PLAG) | Apoptosis↑ | i-NOS↓ Bcl-2↓, Bcl-xl↓, BAD↑ → c-caspase3, c-caspase9↑ | Betulinic acid: 100 mg/kg B-PLAG: 100 mg/kg | Liver cancer | in vivo | [130] | |||
Lipid (BA-loaded magnetoliposomes) | Apoptosis↑ Migration↓ | 25 μM | Breast cancer | MDA-MB-231, MCF7 | [129] | ||||
Curcuma longa | Curcumin | Polymer (CLCs) | Proliferation↓ Apoptosis↑ | Bax ↑, Bcl-2 ↓ | CLCsNPs: Caski→154.59 ug/mL, C33A→144.77 ug/mL, Hela→166.49 ug/mL, SiHa→188.55 ug/mL | Cervical cancer | Caski, C33A, HeLA, SiHa | [136] | |
Polymer (chitosan/PEG-CUR) | Apoptosis↑ Invasion↓ Migration↓ | Bax ↑, Bcl-2 ↓→ c-caspase-3 ↑ → c-PARP ↑ | Curcumin: 10 uM chitosan/PEG-CUR: 10 uM | Pancreatic cancer | PANC-1, Mia Paca-2 | [135] | |||
Lipid (Liposomal-CUR) | Proliferation↓ Apoptosis↑ Angiogenesis↓ | CD31↓, VEGF↓, IL-8↓, PARP↑ | 10 μmol/L In vivo: 40 mg/kg | Colorectal cancer | Colo205 LoVo | [133] | |||
Lipid (EPC-CUR) | Apoptosis↑ | molar ratio of curcumin/EPC 1:14 | Colorectal cancer | HCT116, HCT15 | [134] | ||||
Lipid curcumin-resveratrol-gelucire 50/13-HPβCD (CRG-CD) | Apoptosis↑ Proliferation↓ | CUR-RES-gelucire 50/13-HPβCD : 9.9 μM CUR-RES-gelucire 50/13: 6.9 μM | Colorectal cancer | HCT116 | [137] | ||||
Camellia sinensis | EGCG | Polymeric (EGCG-Loaded FU/HA/PEG-Gelatin NPs) | Apoptosis↑ Anti-tumor efficacy↑ | FU/HA/PEG-gelatin/EGCG:CU = 0.600:0.600:3.750:1.000:0.025 | Prostate cancer | Luc PC3 | [139] | ||
Polymer (EGCG-PLGA-NP) | Apoptosis↑ Proliferation↓ | NF-κB↓→ Bcl-2, Bcl-xL, COX-2, TNF-α, cylcinD1, c-Myc, TWIST1, MMP-2↓ | EGCG: 12.5, 25 μM EGCG-NPs: 12.5, 25 μM | Lung cancer | A549, H1299 | [140] | |||
Lipid (EB-SLN) | Apoptosis↑ Migration↓ | EGCG: 65.4 ± 4.9 μg/mL EGCG-SLN: 6.9 ± 1.1 μg/mL EB-SLN: 3.2 ± 1.7 μg/mL | Breast cancer | MDA-MB-231, B16F10 in vivo (C57/BL6 mice) | [142] | ||||
Lipid (NLC-RGD) | Apoptosis↑ | EGCG-loaded NLC-RGD: 45 μg/mL | Breast cancer | MDA-MB-231 | [143] | ||||
Protein (EGCG-loaded BSA-MNPs) | Apoptosis↑ ROS↑ | Nrf2↑→Keap1↓→HO-1↑→ Bcl-2↓, Bax↑, Bak↑, Bim↑, puma↑ | EGCG-loaded BSA-MNPs: 8 μM | Lung cancer | A549 | [141] | |||
Metal (GNPs) | Apoptosis↑ | Bcl-2↓, Bcl-xL↓, Bax, c-caspase7↑, c-caspase3↑ NF-kb/p65↓ (Nuclear) | 50 μg/mL | Breast cancer Prostate cancer | MCF10-A, MDA-MB-231, RWPE1, PC3 | [144] | |||
Ferula communis | Ferulic acid | Polymer (chitosan-SLNs) | Apoptosis↑ Tumor growth↓ | PCNA, Ki67↓, p-ERK1/2↑→p21, p-Rb ↑ | In vitro: 40 and 25 μM of FA and ASPIn vivo: 75 and 25 mg/kg of FA and ASP | Pancreatic cancer | PANC-1, MIA-PaCa-2 | [150] | |
Metal (FA-Se) | Apoptosis↑ ROS↑ | MMP↓ Caspase 3, Caspase 9 activation ↑ | FA-Se-NPs: 5, 10, 20 μg/ml | Liver cancer | HepG2 | [148] | |||
Metal (ZnO) | Cell cycle arrest↑ Apoptosis↑ Nodular formation↓ | ROS↑, MMP↓, DNA damage↑→ Bcl-2↓, Bcl-xL↓, Bax↑, Bad↑, c-caspase-3↑, c-PARP↑, | Liver cancer | HepG2, Huh-7 | [149] | ||||
Garcinia hanburyi | Gambogic acid | Polymer (Met-PEA-PEG) | ROS↑ Proliferation↓ Apoptosis↑ | 0.1~1.0 μg/mL | Prostate cancer Cervical cancer embryo | PC3, Hela, NIH 3T3 | [154] | ||
Polymer (PEI-PLGA) | Proliferation↓ Apoptosis↑ | pTRAIL/GA-HA/PPNPs → caspase3↑, caspase8↑, survivin↓, Bcl-2↓ | 0.0125~1 μM | Breast cancer | MCF-7, MDA-MB-231, 4T1 | [155] | |||
Polymer (Arg-PEUUs) | Migration ↓ Invasion ↓ | FA/Arg/GA/PEUU → MMP-2, MMP-9↓ | GA: 0.6 µg/mL | Cervical cancer Lung cancer Colorectal cancer | Hela, A549 HCT116 | [156] | |||
Metal (Fe3O4) | Proliferation↓ Apoptosis↑ | PI3K↓→ Akt↓→Bad↓→caspase9,3↑ | 0.25~0.75 µg/mL | Colorectal cancer | LoVo | [157] | |||
Panax ginseng | Ginsenoside Rg3 | Lipid (mPEG-b-P(Glu-co-Phe)) | Apoptosis ↑ Proliferation↓ | PCNA↓, caspase3↑ | Rg3-NPs: 50 μg/mL −1 | Colorectal cancer | SW480, SW620, CL40, CCD-18Co | [162] | |
Metal (Fe3O4-NpRg3) | Survival↑ Proliferation↓ Invasion↓ Immune response↑ | Fe3O4 : 70 mg kg−1 Rg3 : 70 mg kg−1 Fe3O4-Rg3 : 70 mg kg−1 | in vivo | in vivo | [161] | ||||
Ginsenoside Rg5 | Protein (FA-Rg5-BSA NP) | Apoptosis ↑ Proliferation↓ Tumor growth ↓ Cellular uptake↑ | Rg5-BSA NP(pH7.4) < FA-Rg5-BSA NP(pH7.4) | FA-Rg5-BSA: 50 μM, 0.5 mg/kg Rg5-BSA: 50 μM, 0.5 mg/kg | Breast cancer Mouse fibroblast cell | MCF-7 L929 | [163] | ||
Ginsenoside Rh2 | Carbon (Rh2HAZnO) | ROS↑ Apoptosis ↑ | MAPK, p38↑, p53↑→caspase7↑, caspase9↑, BAX↑, ROS↑, PARP↑ | Rh2HAZnO: 20 µg/mL | Lung cancer Colorectal cancer Breast cancer | A549, HT29, MCF7 | [44] | ||
Crocus sativus | Kaempferol | Polymer (kaempferol-PEO-PPO-PEO, kaempferol-PLAG) | Proliferation↓ | Efficacy: Kaempferol < K-PEO-PPO-PEO,K- PLAG | PEO-PPO-PEO: 25 μM PLGA: 25 μM PLAG-PEI: 25 μM Chitosan: 25 μM PAMAM: 25 μM Kaempferol: 25 μM | Ovarian surface epithelial cell Ovarian cancer | IOSE397, A2780/CP70, OVCAR-3 | [166] | |
Lipid (KPF-MNE) | Proliferation↓ Cellular uptake↑ Apoptosis↑ | KPF: 1 μM KPF-MNE: 1 μM | Glioma cell | C6 rat ex vivo in vivo | [169] | ||||
Metal (K-AuNCs) | Proliferation↓ Cytotoxicity↑ | K-Au: 12.5 μg/mL | Lung cancer | HK-2 A549 | [168] | ||||
Gelatin (GNP-KA) | Proliferation↓ Angiogenesis↓ | MMP-2, MMP-9, VEGF↓ | KA: 7.4 μg/mL GNP-KA: 150 μg/mL | Human umbilical vascular cells | HUVEC in vivo | [167] | |||
Solanum lycopersicum | Lycopene | Polymeric (LYC-WPI-NPs) | Apoptosis↑ Bioavailability↑ ROS↑ | LYC-WPI-NPs: 15.0 mg/kg/animal | in vivo | MCF-7 in vivo | [173] | ||
Lipid (poly-ɛ-caprolactone lipid-core) | ROS↑ | ROS↑→ NF-κB↓ | NanoLEG: 200 μg/mL | Breast cancer | MCF-7 HMC-3 | [172] | |||
Metal (rGO-AgNPs) + TSA | ROS↑ Apoptosis↑ DNA damage↑ | MDA↑ GSH↓ MMP↓ p53↑→Bax↑, Bak↑→Bcl-2↓ Rad51↑→ γH2AX↑ | rGO-Ag: 0.30 µM 8TSA: 0.20 µM | Ovarian cancer | SKOV3 | [185] | |||
Metal (LP–AN) | Apoptosis↑ | BcL-2↓ Bax↑→ caspase 8, 3, 9, PARP-1↑ AKT↓→β-catenin↓→ NF-κB↓→MMP-2, MMP-9↓ | AN: 0.16 ppm LP: 0.4 μM | Colorectal cancer Lung fibroblast | HT-29 MRC-5 | [174] | |||
Vitis vinifera | Resveratrol | Polymer (Chitosan-coated RSV-FER-FA-SLNs) | Apoptosis↑Cell cycle arrest↑ | CyclinD1, cdk2, cdk4, cdk6, cyclinE, cyclinB↓ cytochrome C↑→ c-caspase9↑→ c-caspase3↑ | C-RSV-FER-FA-SLN: 10 μg/mL RSV-FER-FA-SLN: 25 μg/mL | Colorectal Cancer | HT-29 | [178] | |
Lipid (EGF DTX/ RSV LPNs) | Apoptosis↑ Proliferation ↓ | In vivo: EGF DTX/RSV LPN: 50 mg/kg In vitro: 0~100 μg/mL | Lung cancer | HCC827, NCIH2135 in vivo | [180] | ||||
Lipid (Res-SLN) | Proliferation ↓ Migration ↓ Invasion ↓ Apoptosis ↑ | c-Myc↓→ Bax/Bcl-2 ↑ → cyclinD1↓ | Resveratrol: 40 μM Res-SLN: 40 μM | Breast cancer | MDA-MB-231 | [181] | |||
Protein (RSV-GNP) | ROS↑ Cell cycle arrest ↑ Apoptosis ↑ | p53 ↑→ Bax/Bcl-2, c-cas-9, -3, p21↑ | Lung cancer | NCI-H460 | [182] | ||||
Protein (RES-BSANP) | Apoptosis ↑ | AIF↑, cytochrome c ↑ → Bax ↓ | RES-BSANP: 50 μM | Ovarian cancer | SKOV3 | [183] | |||
Metal (Rev-AuNPs) | Invasion↓, migration↓, | NF-κB↓→ AP-1↓→ MMP-9↓, COX-2↓ Akt↓, ERK↓→ MMP-9↓, COX-2↓ HO-1↑→ MMP-9↓ | Rev: 10 μM Rev-AuNPs: 10 μM | Breast cancer | MCF-7 | [179] | |||
carbon (oMCNs-RES) | Proliferation↓ Apoptosis↑ | c-caspase3↑, c-PARP↑ | Resveratrol: 100 μM oMCNs-RES: 200 μM | Breast Cancer | MDA-MB-231 | [184] |
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Kim, B.; Park, J.-E.; Im, E.; Cho, Y.; Lee, J.; Lee, H.-J.; Sim, D.-Y.; Park, W.-Y.; Shim, B.-S.; Kim, S.-H. Recent Advances in Nanotechnology with Nano-Phytochemicals: Molecular Mechanisms and Clinical Implications in Cancer Progression. Int. J. Mol. Sci. 2021, 22, 3571. https://doi.org/10.3390/ijms22073571
Kim B, Park J-E, Im E, Cho Y, Lee J, Lee H-J, Sim D-Y, Park W-Y, Shim B-S, Kim S-H. Recent Advances in Nanotechnology with Nano-Phytochemicals: Molecular Mechanisms and Clinical Implications in Cancer Progression. International Journal of Molecular Sciences. 2021; 22(7):3571. https://doi.org/10.3390/ijms22073571
Chicago/Turabian StyleKim, Bonglee, Ji-Eon Park, Eunji Im, Yongmin Cho, Jinjoo Lee, Hyo-Jung Lee, Deok-Yong Sim, Woon-Yi Park, Bum-Sang Shim, and Sung-Hoon Kim. 2021. "Recent Advances in Nanotechnology with Nano-Phytochemicals: Molecular Mechanisms and Clinical Implications in Cancer Progression" International Journal of Molecular Sciences 22, no. 7: 3571. https://doi.org/10.3390/ijms22073571