Specific FRET Probes Sensitive to Chitosan-Based Polymeric Micelles Formation, Drug-Loading, and Fine Structural Features
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents
2.2. Synthesis of Chitosan Grafted with Lipoic Acid (Chit5-LA) and Oleic Acid (Chit5-OA)—Micelles Preparation
2.3. Characterization of Chitosan Grafted with Lipoic Acid (Chit5-LA)
2.4. FRET Probes for Determination of CMC for Micelles Formed from Surfactants and Chit5-LA
2.4.1. Determination of CMC for Micelles Formed from Surfactants
2.4.2. Determination of CMC for Polymeric Micelles
2.4.3. Flow Cytometry for Micelle Formation Study
2.4.4. Release of R6G from Micelles by Addition of Reduced Glutathione as Thiol-Disulfide Exchange Agent (Tumor Microenvironment Model)
2.5. Enzyme Activity Studies for Determination of the Fluorophore Inclusion Degree in Micelles
3. Results
3.1. Article Design
3.2. FRET as an Indicator of Micelle Formation in Surfactants Solution
3.2.1. MUTMAC–R6G Pair
3.2.2. FITC–R6G Pair
3.2.3. Comparison of CMC Values Obtained Using Two FRET Probes and the Literature Data
Surfactant | CPMC, µM | CMC, mM | ||
---|---|---|---|---|
FRET Probe 1: MUTMAC + R6G | FRET Probe 2: FITC + R6G | Literature Data | ||
SDS (sodium dodecyl sulfate) | 15 ± 4 | 3.4 ± 0.1 | 3.2 ± 0.3 | 3.32 ± 0.01 [51] |
Triton X-100 | 16 ± 3 | 0.39 ± 0.05 | 0.27 ± 0.08 | 0.3 ± 0.01 [51] |
Zephirol (benzalkonium chloride) | 4 ± 1 | 0.6 ± 0.1 | 0.7 ± 0.2 | 0.6 mM [52] |
3.3. Determination of the Fluorophore Inclusion Degree in Micelles by Enzymatic Activity
3.4. Formation of Polymeric Micelles as Assessed by FRET Probes
3.4.1. Self-Assembled Amphiphilic Chitosan Grafted with Lipoic and Oleic Acid Residues
3.4.2. Polymeric Micelles Formation and S-S Stitching Detection Using MUTMAC–R6G Probe
3.5. A Comparison of the Proposed FRET Probe Technique with Other Techniques Described in the Literature to Study the Properties of Micelles
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Micelle * | Grafting Degree, % | Mw of One Polymeric Unit, kDa | CMC, nM | Hydrodynamic Diameter **, nm | Zeta Potential, mV |
---|---|---|---|---|---|
Chit5-OA | 18 ± 2 | 6.7 ± 0.8 | 8 ± 2 | 300–450 | +5 ± 1 |
Chit5-LA nonstitched | 24 ± 3 | 6.4 ± 0.3 | 50 ± 10 | 300–350 | +20 ± 3 |
Chit5-LA S-S stitched | 45 ± 6 (is about 7 residues of Chit5-branches) | 16 ± 2 | 230–280 | +15 ± 2 |
Method | CMC Determination | CPMC Determination | Aggregation Number Determination | Size Determination | Robustness | Applicability to Different Types of Micelles | Expressiveness |
---|---|---|---|---|---|---|---|
Conductometry [39,58,59] | ± | − | − | − | + | ± | + |
Surface tension [51,60,61] | + | − | − | − | ± | − | + |
Densitometry [59] | ± | − | − | − | ± | − | + |
NMR spectrometry [62] | + | ± | ± | − | + | ± | − |
UV/VIS spectroscopy [63] | + | − | − | − | + | ± | + |
Fluorometric methods (including pyrene probe) [32,61,64,65,66] | ++ | + | ± | ± | + | + | + |
Atomic force and electron microscopy [67] | ± | − | − | ++ | ± | + | − |
FRET probes | + | + | ± | ± | + | ++ | + |
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Zlotnikov, I.D.; Savchenko, I.V.; Kudryashova, E.V. Specific FRET Probes Sensitive to Chitosan-Based Polymeric Micelles Formation, Drug-Loading, and Fine Structural Features. Polymers 2024, 16, 739. https://doi.org/10.3390/polym16060739
Zlotnikov ID, Savchenko IV, Kudryashova EV. Specific FRET Probes Sensitive to Chitosan-Based Polymeric Micelles Formation, Drug-Loading, and Fine Structural Features. Polymers. 2024; 16(6):739. https://doi.org/10.3390/polym16060739
Chicago/Turabian StyleZlotnikov, Igor D., Ivan V. Savchenko, and Elena V. Kudryashova. 2024. "Specific FRET Probes Sensitive to Chitosan-Based Polymeric Micelles Formation, Drug-Loading, and Fine Structural Features" Polymers 16, no. 6: 739. https://doi.org/10.3390/polym16060739