Bactericidal Activity of Non-Cytotoxic Cationic Nanoparticles against Clinically and Environmentally Relevant Pseudomonas spp. Isolates
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Instruments
2.2. Microbiology
2.2.1. Microorganisms
2.2.2. Determination of the MIC
2.2.3. Killing Curves
2.3. Evaluation of G5-PDK Cytotoxicity
2.3.1. Cell Culture
2.3.2. Viability Assay
2.4. Statistical Analyses
3. Results
3.1. Synthesis and Spectrophotometric Characterization of Lysine-Modified Cationic Dendrimer G5-PDK
3.1.1. Synthesis of the Uncharged Fifth-Generation Polyester-Based Inner Scaffold of G5-PDK (G5-PD-OH)
3.1.2. Synthesis of Lysine-Modified Boc-Protected Dendrimer G5-PD-BK
3.1.3. Acidic Deprotection of G5-PD-BK to Obtain G5-PDK * 128 HCl
3.2. Antibacterial Properties
3.2.1. MICs of G5-PDK
3.2.2. Time-Killing Curves
3.3. Evaluation of Cytotoxicity of G5-PDK on HaCaT Human Keratinocytes Cells
Dose- and Time-Dependent Cytotoxicity Experiments
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Analysis | G5-PD-OH | G5-PD-BK | ||
---|---|---|---|---|
FTIR (cm−1) | OH C-H alkyl C=O esters | 3436 2936 1737 | NH C-H alkyl C=ONH urethane -C=O esters NH banding | 3380 2870, 2932, 2979 1710 1747 1727 |
1H NMR (400 MHz, DMSO-d6) (ppm) | CH3 G1-G5, s, 186H CH2 PD, m, 2H CH2OH, dd, 128H CH2O PD, m, 2H CH2O PD, m, 2H CH2O DR, m, 120H OH, br s, 64H | 1.01, 1.16, 1.18, 1.23, 1.34 1.70 3.52 3.56 3.98 4.08–4.18 4.37 | CH3 G1-G5, CH2O PD, CH2CH2CH2lys, m, 572H CH3 Boc, s, 576H CH3 Boc, s, 576H CH2NH lys, m, 128H CH2O PD, m, 2H CH2O DR + PD + CHNH lys, m, 314H αNHBoc + εNHBoc lys, m, 128H | 0.95–1.90 1.43 1.44 3.10 3.56 4.25 4.70–5.50 |
13C NMR (100 MHz, DMSO-d6) (ppm) | C=O G1-G5 CH2O G1-G5 Quaternary C G5 Quaternary C G1-G4 CH3 G1-G5 | 173.94, 171.73 64.27, 63.55 50.13 46.12 17.05, 16.61 | C=O esters C=ONH urethane Quaternary C Boc CH2O G1-G5 CHNH Quaternary C G1-G5 CH2NH CH2 lys CH3 Boc CH3 G1-G5 | 172.32 156.17, 155.63 79.80, 79.02 65.60–65.41 53.37 46.42 40.04 31.84, 29.57, 22.57 28.47, 28.36 17.90–14.20 |
Elemental Analysis | C, H | 51.71, 7.01 * 51.67, 6.98 § | C, H, N | 56.78, 8.30, 6.00 * 56.76, 8.18, 6.34 § |
Analysis | G5-PDK | ||
---|---|---|---|
FTIR (cm−1) | NH3+ -C=O esters NH banding | 3431 1744 1635 | |
1H NMR (400 MHz, DMSO-d6) (ppm) | CH3 G1-G5 + CH2CH2CH2 lys, m, 570H CH2 PD, m, 2H CH2NH3+ Lys, m, 128 CH2O PD, 3.56, 2H, CHNH3+ lys, m, 64H CH2O PD DR + CHNH3+ lys, m, 250H αNH3+ lys, br s,192H εNH3+ lys, br s, 192H | 1.03–1.99 1.70 2.76 3.56 3.99 4.10–4.50 8.20 8.82 | |
13C NMR (DMSO-d6, 100 MHz) (ppm) | CH3 G1-G5 CH2CH2CH2 lys CH2NH3+ Quaternary C G1-G5 CHNH3+ CH2O G1-G5 C=O | 19.33 23.14, 28.01, 31.01 40.02 47.70 53.55 67.65–67.82 170.68–173.33 | |
Elemental Analysis | C, H, N | 41.78, 7.30, 9.10, 22.11 * 41.56, 7.00, 8.90, 22.53 § | |
1H NMR | MW | 20145.3 19961.2 ± 480.2 | |
Volumetric titration | |||
DLS 1 Analysis | Z-Ave 2 (nm) PDI 3 Z-potential 4 (ζ-p) | 203.0 ± 2.6 5 0.282 ± 0.028 5 +19.2 ± 7.3 | |
Potentiometric Titration | Max dpH/dV 5 HCl 0.1N (mL) 6 pH 7 | 10.75 0.6 6.85 | 4.0 1.2 4.80 |
Strains | MIC (µM (µg/mL)) |
---|---|
P. aeruginosa | >6.4 (>128) |
P. fluorescens SMI1 | 0.8 (16) |
P. putida SMA1 | 0.8 (16) |
S. maltophylia | >25.4 (>512) |
Strains | MIC µM (µg/mL) | Selectivity Index 2 |
---|---|---|
P. aeruginosa 1 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 2 # 3 | 6.4 (128) | 13 |
P. aeruginosa 4 # 3 | 6.4 (128) | 13 |
P. aeruginosa 7 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 9 # 3 | 6.4 (128) | 13 |
P. aeruginosa 10 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 11 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 12 # 3 | 6.4 (128) | 13 |
P. aeruginosa 13 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 14 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 16 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 17 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 18 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 19 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 20 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 244 § 3 | 1.6 (32) | 51 |
P. aeruginosa 247 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 248 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 256 # 3 | 6.4 (128) | 13 |
P. aeruginosa 259 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 402 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 403 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 405 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 426 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 427 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 428 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 432 § 3 | 1.6 (32) | 51 |
P. aeruginosa 433 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 434 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 435 * 3 | >6.4 (>128) | <13 |
P. aeruginosa 436 * 3 | >6.4 (>128) | <13 |
P. aeruginosa ATCC 27853 * 3 | >6.4 (>128) | <13 |
P. fluorescens A8 # 4 | 0.8 (16) | 101 |
P. fluorescens SMM8 # 4 | 1.6 (32) | 51 |
P. fluorescens SMI1 # 4 | 0.8 (16) | 101 |
P. fluorescens SMI2 # 4 | 0.8 (16) | 101 |
P. fluorescens SMI6 # 4 | 1.6 (32) | 51 |
P. fragi G2 # 4 | 1.6 (32) | 51 |
P. oleovorans # 3 | 0.4 (8) | 202 |
P. putida 262 * 3 | 3.2 (64) | 25 |
P. putida 407 * 3 | 3.2 (64) | 25 |
P. putida 409 * 3 | 3.2 (64) | 25 |
P. putida 410 * 3 | 6.4 (128) | 13 |
P. putida SMA1 # 4 | 0.8 (16) | 101 |
P. straminea A5 # 4 | 1.6 (32) | 51 |
P. straminea A7 # 4 | 1.6 (32) | 51 |
P. straminea A13 # 4 | 1.6 (32) | 51 |
P. syringae # 4 | 0.2 (4) | 404 |
Label * | µM | Cell Viability (%) 24 h | Cell Viability (%) 12 h |
---|---|---|---|
1 | 100 | 35.9454 | 41.34742 |
2 | 75 | 57.4335 | 83.17176 |
3 | 50 | 68.9837 | 106.293 |
4 | 25 | 94.8178 | 124.5387 |
5 | 10 | 108.6001 | 126.6832 |
6 | 5 | 131.3011 | 98.12797 |
7 | 1 | 122.8936 | 94.55272 |
Data Set | Outliers | LD50 (µM) | SI | |
---|---|---|---|---|
Lables | Values (µM,%) | |||
12 | 6, 7 | 5, 98.12797 1, 94.55272 | 95.7 | 15–478 |
24 | 6 | 5, 131.3011 | 80.8 | 13–404 |
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Schito, A.M.; Piatti, G.; Caviglia, D.; Zuccari, G.; Zorzoli, A.; Marimpietri, D.; Alfei, S. Bactericidal Activity of Non-Cytotoxic Cationic Nanoparticles against Clinically and Environmentally Relevant Pseudomonas spp. Isolates. Pharmaceutics 2021, 13, 1411. https://doi.org/10.3390/pharmaceutics13091411
Schito AM, Piatti G, Caviglia D, Zuccari G, Zorzoli A, Marimpietri D, Alfei S. Bactericidal Activity of Non-Cytotoxic Cationic Nanoparticles against Clinically and Environmentally Relevant Pseudomonas spp. Isolates. Pharmaceutics. 2021; 13(9):1411. https://doi.org/10.3390/pharmaceutics13091411
Chicago/Turabian StyleSchito, Anna Maria, Gabriella Piatti, Debora Caviglia, Guendalina Zuccari, Alessia Zorzoli, Danilo Marimpietri, and Silvana Alfei. 2021. "Bactericidal Activity of Non-Cytotoxic Cationic Nanoparticles against Clinically and Environmentally Relevant Pseudomonas spp. Isolates" Pharmaceutics 13, no. 9: 1411. https://doi.org/10.3390/pharmaceutics13091411