Exploring the Potential of Lapatinib, Fulvestrant, and Paclitaxel Conjugated with Glycidylated PAMAM G4 Dendrimers for Cancer and Parasite Treatment
Abstract
:1. Introduction
2. Results and Discussion
2.1. Syntheses and Characterization of Dendrimer Conjugates
2.2. Cellular Accumulation
2.3. Cytotoxicity
2.4. Proliferation
2.5. Effect on the Worm Survival
3. Materials and Methods
3.1. Dendrimer Synthesis and Characterization
3.1.1. Spectroscopy
3.1.2. Conjugate Size and ζ Potential
3.2. Syntheses of Conjugates
3.2.1. Conjugates of Paclitaxel (P), Lapatinib (L), and Fulvestrant (F) (Primary Conjugates)
3.2.2. Binary and Ternary Conjugates of G4* with Paclitaxel, Lapatinib and Fulvestrant
3.3. Biological Studies
3.3.1. Biochemical Reagents, Cell Lines and Materials
3.3.2. Cell Cultures
3.3.3. Toxicity Assays
3.3.4. Proliferation Assay
3.3.5. Cellular Accumulation of Labeled Conjugates
3.3.6. Toxicity to Caenorhabditis Elegans
3.3.7. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Conjugate | MW [kDa] | Size (SD) [nm] | Polydispersity Index PDI (SD) | ζ (SD) [mV] |
---|---|---|---|---|
G4*126gl G4 | 19.1 | 5.12 (0.25) | 0.080 (0.002) | 4.35 (0.28) |
G4*4P109gl G4P | 26.4 | 99.20 (7.28) | 0.134 (0.016) | 13.57 (0.43) |
G4*13F64gl G4F | 27.6 | 138.23 (6.24) | 0.155 (0.022) | 38.02 (0.54) |
G4*13L85gl G4L | 28.8 | 113.13 (4.64) | 0.112 (0.014) | 40.29 (0.74) |
G4*4P10L98gl G4PL | 31.7 | 95.20 (4.46) | 0.125 (0.010) | 19.92 (0.53) |
G4*4P10F98gl G4PF | 32.0 | 113.41 (5.48) | 0.128 (0.015) | 29.29 (0.72) |
G4*4P11F11L74gl G4PFL | 37.5 | 105.47 (5.39) | 0.159 (0.018) | 34.33 (0.65) |
IC50 [nM] NR Assay | |||
---|---|---|---|
A549 | U-118 MG | HaCaT | |
Paclitaxel | 50.35 | 55.56 | 2.53 |
Fulvestrant | ≫100,00 * | ≫100,000 * | ≫100,000 * |
Lapatinib | 16,701.61 | 14,878.63 | 6150.48 |
G4P | ≫320 * ≫1280 * p | 25.28 101.12 p | 1.63 6.52 p |
G4F | ≫1000 * ≫130,000 * f | ≫10,000 * ≫130,000 * f | 2927.15 38,052.97 f |
G4L | 1324.05 17,212.75 l | 54,395 6527.4 l | 57.87 765.31 l |
G4PFL | ≫400 * ≫400 * p ≫4400 * fl | 78.70 314.80 p 865.70 fl | 9.53 38.12 p 104.83 fl |
IC50 [nM] XTT Assay | |||
G4P | ≫320 ≫1280 * p | 3.14 12.56 p | 0.99 3.96 |
G4F | >20,000 >260,000 f | 6062.64 78,814.32 f | 1282.15 16,667.95 f |
G4L | 3885.91 50,516.83 l | 1147.86 14,922.18 l | 76.90 999.70 l |
G4PFL | >1600 >6400 p >17,600 fl | 9.45 37.80 p 103.95 fl | 2.00 8.00 p 22.00 fl |
Compound | LC50 [µM] |
---|---|
Mebendazole | 4.00 |
G4P | >24.00 |
G4F | 12.50 |
G4L | 14.80 |
G4PFL | 6.75 |
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Uram, Ł.; Wróbel, K.; Walczak, M.; Szymaszek, Ż.; Twardowska, M.; Wołowiec, S. Exploring the Potential of Lapatinib, Fulvestrant, and Paclitaxel Conjugated with Glycidylated PAMAM G4 Dendrimers for Cancer and Parasite Treatment. Molecules 2023, 28, 6334. https://doi.org/10.3390/molecules28176334
Uram Ł, Wróbel K, Walczak M, Szymaszek Ż, Twardowska M, Wołowiec S. Exploring the Potential of Lapatinib, Fulvestrant, and Paclitaxel Conjugated with Glycidylated PAMAM G4 Dendrimers for Cancer and Parasite Treatment. Molecules. 2023; 28(17):6334. https://doi.org/10.3390/molecules28176334
Chicago/Turabian StyleUram, Łukasz, Konrad Wróbel, Małgorzata Walczak, Żaneta Szymaszek, Magdalena Twardowska, and Stanisław Wołowiec. 2023. "Exploring the Potential of Lapatinib, Fulvestrant, and Paclitaxel Conjugated with Glycidylated PAMAM G4 Dendrimers for Cancer and Parasite Treatment" Molecules 28, no. 17: 6334. https://doi.org/10.3390/molecules28176334