Progress in the Surface Functionalization of Selenium Nanoparticles and Their Potential Application in Cancer Therapy
Abstract
:1. Introduction
2. Synthesis, Surface Functionalization, and Stability of SeNPs
2.1. Synthesis of SeNPs
2.2. Surface Functionalization of SeNPs
2.2.1. Polysaccharides Functionalized SeNPs
2.2.2. Protein Functionalized SeNPs
2.2.3. Other Biomolecules Functionalized SeNPs
Name | Biomolecules | Reaction Conditions | Size | Stability Conditions Tested | Stability | Ref. |
---|---|---|---|---|---|---|
Polysaccharides | ||||||
T70-SeNPs | Dextran 70,000 | T70: 5 mg/mL, 20 mL; Na2SeO3: 200 mM, 250 μL; Vc: 200 mM, 1.25 mL; Temperature: 25℃; Time: 12 h | 110.3 ± 30.2 nm | Storage stability: 0, 1, 3, 6 months of storage at 4 °C | The freeze-dried powder of T70-SeNPs kept stable for 6 months at 4 °C, while the size of T70-SeNPs solution increased from 117.5 ± 30.4 to 178.5 ± 43 nm in the second month | [55] |
PSP-SeNPs | Polygonatum sibiricum polysaccharide | PSP: 5 mg/mL; Na2SeO3: 50 mM, 1 mL; Vc: 200 mM, 1 mL; Temperature: 25 °C; Time: 30 min | 114 nm | Storage stability: 0, 1, 5, 10, 20, 30 days of storage at 4 °C; Thermal stability: 25 °C, 50 °C, 70 °C, 90 °C for 1 h; pH stability: pH 2–10 for 1 h; Ionic strength stability: 10, 50, 100 mM NaCl for 1 h | PSP-SeNPs were stable for 20 days of storage at 4 °C and stable at pH 3–10, but easily aggregated in 100 mM NaCl | [56] |
ORPS-SeNPs | Oudemansiella raphanipies polysaccharide | ORPS: 1 mg/mL; Na2SeO3: 0.1 M, 0.3 mL; TW-80: 2 mg/mL; Vc: 0.1 M, 1.2 mL; Temperature: 30 °C; Time: 4 h; Dark condition | 60 nm | Storage stability: 0, 15, 30, 60, 90, 120 days of storage at 4 °C, 25 °C, 37 °C; pH stability: pH 2–10 | ORPS-SeNPs were stable at 4 °C for at least 90 days and stable at pH 4–10 | [57] |
SPs-SeNPs | Spirulina platensis polysaccharide | SPs: 100 mg/mL; Na2SeO3: 2 mM; Vc: 6 mM; Time: 6 h | 73.42 nm | Storage stability: 0, 5, 15, 30, 45, 60, 75, 90 days of storage at 4 °C | SPs-SeNPs were stable for 75 days at 4 °C | [58] |
GLP-SeNPs | Grateloupia Livida polysaccharide | GLP: 1 mg/mL, 5 mL; Na2SeO3: 0.01 M, 5 mL; Vc: 0.04 M, 5 mL; Temperature: 45 °C; Time: 3 h | 115.54 nm | Storage stability: 0, 5, 10, 15, 20, 25, 30 days of storage at 4 °C and 25 °C | GLP-SeNPs were stable at 4 °C after 30 days of storage and only kept stable for 15 days at 25 °C | [28] |
AF1-Se nanocomposite | A highly-branched β-(1→3)-D-glucan | AF1: 1 mg/mL, 100 mL; Na2SeO3: 0.1 M, 1 mL; Vc: 0.2 M, 2 mL; Temperature: 25 °C; Time: 24 h | 92 nm | Storage stability: 1 day and 16 months of storage at room temperature | AF1-Se nanocomposite exhibited excellent stability during 16 months of storage | [59] |
PUP-SeNPs | Polyporus umbellatus polysaccharide | PUP: 2.5 mg/mL, 0–8 mL; Na2SeO3: 50 mM, 1 mL; Vc: 20 mM, 10 mL; Temperature: 30 °C; Time: 12 h; Dark condition | 82.5 nm | Storage stability: Illumination (dark and 2500 ± 200 Lx), temperature (4 °C, 25°C, 37 °C), time (0–120 days); pH stability: 2–12 | PUP-SeNPs possessed good stability at 4 °C in dark conditions for 84 days and were stable at pH 4–12 | [60] |
CS-SeNPs | Chitosan | CS: 10 mg/mL, 1 mL; H2SeO3: 20 mM, 1 mL; Vc: 80 mM, 1 mL | 387.31 ± 8.13 nm | Storage stability: 0, 5, 10, 15, 20, 25, 30 days of storage at 4 °C; Thermal stability: 30 °C, 50 °C, 70°C, 90 °C for 1 h; pH stability: pH 3–9 for 1 h; Ionic strength stability: 10, 100, 500 mM NaCl for 1 h | CS-SeNPs exhibited good thermal stability and storage stability for 30 days, but easily aggregated in 500 mM NaCl or at pH > 8 | [25] |
CPP-SeNPs | Fructose-enriched polysaccharide from Codonopsis pilosula | CPP: 2 mg/mL, 5 mL; Na2SeO3: 1.2 M; Vc: 4.8 M; The mass ratio of Na2SeO3/CPP: 1:20; Temperature: 25 °C; Dark condition | 75 nm | Storage stability: 0, 7, 14, 21, 28, 35 days of storage at 4 °C | CPP-SeNPs showed superior stability at 4 °C for at least 35 days | [61] |
GLP-SeNPs | Polysaccharides of Gracilaria lemaneiformis | GLP: 2 mg/mL; Na2SeO3: 0.01 M; Vc: 0.04 M; Temperature: 40 °C; Time: 4 h; Dark condition | 92.5 nm | Storage stability: 0, 7, 14, 21, 28, 42 days of storage at 4 °C and 25 °C in dark conditions; pH stability: pH 3, 5, 7, 9 for 1 h; Ionic strength stability: 50, 100, 150, 200 mM for 1 h | GLPs-SeNPs were stable at 4 °C under dark conditions for 42 days and kept stable in 50–200 mM ion strengths and at a pH range from 3 to 10 | [62] |
SFPS-SeNPs | Polysaccharides from Sargassum fusiforme | SFPS: 1 mg/mL; Na2SeO3: 0.01 M; Vc: 0.04 M; Temperature: 50 °C; Time: 4 h | 60 nm | Storage stability: 0, 7, 14, 21, 30, 40 days of storage at 4 °C | SFPS-SeNPs remained highly stable at 4 °C for 40 days | [63] |
APS-SeNPs | Astragalus polysaccharide | APS: 2 mg/mL, 10 mL; Na2SeO3: 10 mM, 2.4 mL; Vc: 40 mM, 2.4 mL; Temperature: 25 °C; Time: 4 h | 62.3 nm | Storage stability: 0, 7, 14, 21, 28, 35 days of storage at 4 °C | APS-SeNPs exhibited good stability for 35 days at 4 °C | [64] |
PEC-SeNPs | Pectin | PEC: 1 mg/mL, 200 mL; Na2SeO3: 0.1 M; Vc: 0.2 M, 1 mL; Temperature: 25 °C; Time: 24 h | 41 nm | Storage stability: 0, 5, 10, 15, 20, 25, 30 days of storage at 4 °C pH stability: pH 3, 4, and 5 during the storage time (0–30 days) | PEC-SeNPs were highly stable at pH > 4.0 for at least 1 month | [32] |
SeNPs-C/C | Chitosan/citrate gel | CS: 10 mg/mL; Na2SeO3: 40 mg/mL; Vc: 40 mg/mL | 1–30 μm | Storage stability: 0, 5, 10 days of storage at 60 ± 1 °C, 80 ± 5% RH, and 5000 ± 500 Lx (Stress testing); 1, 2, 3, 6 months storage at 40 ± 2 °C, 75 ± 5% RH, dark (Accelerated testing) | SeNPs-C/C exhibited excellent stability after 6 months of storage in a simulated package environment (40 ± 2 °C, 75 ± 5% RH, dark) | [65] |
Proteins | ||||||
Blg-SeNPs | Beta-lactoglobulin | Blg: 10 mg/mL, 1 mL; Na2SeO3: 0.06 M, 1 mL; Vc: 0.3 M, 5 mL; Time: 30 min | 36.8 nm | Storage stability: 0, 30 days of storage at 4 °C or 25 ± 1 °C; pH stability: pH 2.5, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 | Blg-SeNPs were stable in acidic or neutral to basic solutions (pH 2.5–3.5 or 6.5–8.5) at 4 °C for 30 days | [47] |
BSINPs | Bovine serum albumin | BSA: 20.63 mg/mL, 40 mL; Na2SeO3: 20 mM, 10 mL; Glutathione: 25 mM, 40 mL; Time: 1 h | 40 nm | Storage stability: 0, 1, 2, 3, 4 weeks of storage | BSINPs remained around the initial particle size without aggregation or precipitation over 4 weeks | [66] |
Other biomolecules | ||||||
EWP-SeNPs | Egg white polypeptide | EWP: 35 mg/mL; Na2SeO3: 1.038 mg/mL; Temperature: 82 °C; Time: 3.5 h | 30–50 nm | Storage stability: 0, 8, 30 days of storage at 4 °C; pH stability: pH 2, 4, 6, 8, 10 for 8 and 30 days | EWP-SeNPs showed excellent stability in an alkaline environment (pH = 10) for 30 days at 4 °C | [67] |
TP-SeNPs | Tilapia polypeptide | TP: 20 mg/mL; Na2SeO3: 0.692 mg/mL; Temperature: 50 °C; Time: 21 h | 200 nm | Storage stability: 0, 8 days of storage at 4 °C; pH stability: pH 2, 4, 6, 8, 10 for 8 days at 4 °C | TP-SeNPs were relatively stable in an alkaline environment (pH = 8) after 8 days of storage at 4 °C | [49] |
Ppm-SeNPs | Peanut meal peptides mixture | Ppm: 3–4 mg/mL; Na2SeO3: 1 mM; Vc: 4 mM; Temperature: 55℃; Time: 6 h | 140 nm | Storage stability: Two months of storage at 4 °C and 25 ± 1 °C; Thermal stability: 90 °C for 1, 3, and 6 h; pH stability: pH 2, 6, 10 for 2 weeks at 4 °C | Ppm-SeNPs exhibited good thermal stability and alkali resistance, and were stable for 60 days at 4 °C | [48] |
PSP-SeNPs | Polysaccharide-protein complex | PSP: 0.08%; Na2SeO3: 1 mM; Vc: 4 mM; Temperature: 25 °C | 63.33 nm | Storage stability: 0, 4, 8, 12 months of storage at 4 °C | PSP-SeNPs remained stable for 12 months at 4 °C | [68] |
Bc@SeNPs | Betacyanins | Bc: 14 mg/mL, 5 mL; Na2SeO3: 7 mg/mL, 5 mL; Vc: 30 mg/mL, 5 mL; Temperature: 4 °C; Time: 24 h | 133 nm | Storage stability: 0, 5, 10, 15, 20, 25, 30 days of storage at 4 °C | Bc@SeNPs maintained good stability in an aqueous solution at 4 °C for 30 days | [69] |
2.3. The Stability of Functionalized SeNPs
3. Targeting Strategies for SeNPs
3.1. Achieving Targeting by Avoiding Reticuloendothelial System (RES)
3.2. Tumor-Activated Targeting
3.2.1. Small Molecules-Based Targeting SeNPs
3.2.2. Carbohydrate-Based Targeting SeNPs
3.2.3. Peptides-Based Targeting SeNPs
3.2.4. Antibodies-Based Targeting SeNPs
3.2.5. Aptamers-Based Targeting SeNPs
Name | Ligand | Receptors | Endocytosis Mechanism | Biochemical Mechanism | Ref. |
---|---|---|---|---|---|
Small molecules-based | |||||
FA-SeNPs | Folic acid | Folate receptors | Clathrin and caveolin-mediated endocytosis | ROS overproduction and mitochondrial depolarization | [92] |
SeNPs@TMC-FA | Folic acid | Folate receptors | Folate receptor-mediated endocytosis | Regulation of caspase-3 and PARP | [96] |
LA-PLL-SeNPs | Lactobionic acid | ASGPR | ASGPR-mediated endocytosis | N/A | [101] |
Carbohydrate-based | |||||
GA-SeNPs | Galactose | Lectin receptors | Clathrin-mediated endocytosis | Activating caspase signaling and Bcl-2 family proteins | [102] |
GLP-SeNPs | Gracilaria lemaneiformis polysaccharide | αvβ3 integrin | αvβ3 integrin-mediated endocytosis | Downregulation of intracellular reactive oxygen species and activation of p53, MAPKs, and AKT pathways | [110] |
LNT-SeNPs | lentinan | TLR4/TNF receptor | Caveolae-mediated endocytosis | Regulation of mitochondrial membrane fusion pathway, mediated by factor 3 (TRAF3)/mitofusin-1 (MFN1) protein complex | [111] |
Peptides-based | |||||
RGD-NPs | RGD peptide | αvβ3 integrin receptor | αvβ3 integrin-mediated endocytosis | Induction of apoptosis and cell cycle arrest in HUVECs via suppression of VEGF-VEGFR2-ERK/AKT signaling axis | [113] |
GE11-Se NPs | GE11 peptide | EGFR | Lipid raft-mediated and clathrin-mediated endocytic pathway | Induction of reactive oxygen species production, activation of the mitochondria-dependent pathway, and inhibition of EGFR-mediated PI3K/AKT, and Ras/Raf/MEK/ERK pathways | [117] |
Antibodies-based | |||||
HER2@NP | HER2 antibody | HER2 receptors | Receptor-mediated endocytosis | Triggered DNA damage-mediated p53 signaling pathways | [123] |
OX26-PEG-Se NPs | Monoclonal antibody (OX26) | Anti-transferrin receptor | Transferrin receptor-mediated endocytosis | Regulation of cellular metabolic state (TSC1/TSC2, p-mTOR, mTORC1), oxidative defense system (FoxO1, β-catenin/Wnt, Yap1), inflammatory reactions (jak2/stat3, Adamts-1), autophagy and apoptotic cell death (Mst1, ULK1, Bax, caspase-3 and Bcl-2) | [124] |
Aptamers-based | |||||
PEI-PEG-5TR1 aptamer coated SeNPs | 5TR1 aptamer | Mucin-1-glycoform | MUC1 receptor-mediated endocytosis. | N/A | [128] |
4. SeNPs as Delivery Vehicles
4.1. Single Delivery
4.2. Co-Delivery
5. Conclusions and Perspective
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug/Gene Loaded | Nanocarrier | Release Properties | Effects | Ref. |
---|---|---|---|---|
Doxorubicin | Folic acid-N-trimethyl chitosan stabilized SeNPs | The release rate was 12.3% and 54.1% at pH 7.4 and 5.3 within 2 h | Induce cell death through the apoptosis pathway by the involvement of caspase-3 and PARP proteins. | [96] |
Paclitaxel | Hyaluronic acid-modified SeNPs | The release rates were 45.7% and 59.4% in pH 7.4 and 6.8 | Activate the caspase-3-related apoptosis pathway | [132] |
Cisplatin | Chitosan-coated SeNPs | The release rates reached 50% at 12 h in pH 5.3 while less than 15% was released at pH 7.4 | Reduce ROS levels to prevent HIF-1 activation | [133] |
Curcumin | Pectin-decorated SeNPs | The cumulative release was 60% at pH 3.0 and 17% at pH 7.0 within 8 h | Inhibit the growth of HepG2 cells | [134] |
Seamol | Polyethylene-glycol-functionalized SeNPs | The release rate reached 65.4% at 24 h and 84.7% at 48 h (pH 5.4) | Induce apoptosis by down-regulating of Bcl-2 and procaspase-3, up-regulating Bax and PARP | [135] |
siRNA | Layer-by-layer Se-based nanocomplexes | The release rate was only 35% after 7 days | Induce around 32% apoptosis in H1299 cancer cells | [136] |
siRNA/cisplatin | Amine-terminated generation 5 polyamidoamine dendrimers-modified SeNPs | The accumulated siRNA released rate reached 80% | Induce apoptosis involving the AKT and ERK signaling pathways | [137] |
Doxorubicin/ indocyanine green | RC-12 and PG-6 peptides functionalized SeNPs | The release ratio was 82.5% for pH 5.3 and 36% for pH 7.4 with NIR laser irradiation | Induce apoptosis by triggering ROS overproduction | [138] |
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Chen, W.; Cheng, H.; Xia, W. Progress in the Surface Functionalization of Selenium Nanoparticles and Their Potential Application in Cancer Therapy. Antioxidants 2022, 11, 1965. https://doi.org/10.3390/antiox11101965
Chen W, Cheng H, Xia W. Progress in the Surface Functionalization of Selenium Nanoparticles and Their Potential Application in Cancer Therapy. Antioxidants. 2022; 11(10):1965. https://doi.org/10.3390/antiox11101965
Chicago/Turabian StyleChen, Wanwen, Hao Cheng, and Wenshui Xia. 2022. "Progress in the Surface Functionalization of Selenium Nanoparticles and Their Potential Application in Cancer Therapy" Antioxidants 11, no. 10: 1965. https://doi.org/10.3390/antiox11101965
APA StyleChen, W., Cheng, H., & Xia, W. (2022). Progress in the Surface Functionalization of Selenium Nanoparticles and Their Potential Application in Cancer Therapy. Antioxidants, 11(10), 1965. https://doi.org/10.3390/antiox11101965