Designing Functionalized Polyelectrolyte Microcapsules for Cancer Treatment
Abstract
:1. Introduction
2. Materials and Methods
2.1. Synthesis of CaCO3 Microbeads
2.2. Formation of Core/Shell and Shell Polyelectrolyte Microcapsules
2.3. Functionalization of the Microbeads and Microcapsules with Doxorubicin
2.4. Modification of the Microcapsule Shell with Quantum Dots
2.5. Characterization of Microbeads and Microcapsules with Different Structures
2.6. Efficiency of the Incorporation of Quantum Dots into the Polyelectrolyte Shell
2.7. Analysis of the Kinetics of Doxorubicin Release
2.8. Statistical Analysis
3. Results and Discussion
3.1. Obtaining Doxorubicin-Free and Doxorubicin-Containing Microbeads and Microcapsules with Different Structures
3.2. Functionalization of Microcapsules with Quantum Dots
3.3. Release of Doxorubicin from Microbeads and Microcapsules with Different Structures
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Chang, D.; Ma, Y.; Xu, X.; Xie, J.; Ju, S. Stimuli-Responsive Polymeric Nanoplatforms for Cancer Therapy. Front. Bioeng. Biotechnol. 2021, 9, 528. [Google Scholar] [CrossRef]
- Liu, S.; Lin, T.-P.; Li, D.; Leamer, L.; Shan, H.; Li, Z.; Gabbaï, F.P.; Conti, P.S. Lewis Acid-Assisted Isotopic 18F-19F Exchange in BODIPY Dyes: Facile Generation of Positron Emission Tomography/Fluorescence Dual Modality Agents for Tumor Imaging. Theranostics 2013, 3, 181–189. [Google Scholar] [CrossRef] [Green Version]
- Kaufman, G.; Boltyanskiy, R.; Nejati, S.; Thiam, A.R.; Loewenberg, M.; Dufresne, E.R.; Osuji, C.O. Single-step microfluidic fabrication of soft monodisperse polyelectrolyte microcapsules by interfacial complexation. Lab Chip 2014, 14, 3494–3497. [Google Scholar] [CrossRef]
- Nifontova, G.; Ramos-Gomes, F.; Baryshnikova, M.; Alves, F.; Nabiev, I.; Sukhanova, A. Cancer Cell Targeting With Functionalized Quantum Dot-Encoded Polyelectrolyte Microcapsules. Front. Chem. 2019, 7, 34. [Google Scholar] [CrossRef]
- Kolesnikova, T.A.; Kiragosyan, G.; Le, T.H.N.; Springer, S.; Winterhalter, M. Protein A Functionalized Polyelectrolyte Microcapsules as a Universal Platform for Enhanced Targeting of Cell Surface Receptors. ACS Appl. Mater. Interfaces 2017, 9, 11506–11517. [Google Scholar] [CrossRef] [PubMed]
- Simioni, A.R.; De Jesus, P.C.C.; Tedesco, A.C. Layer-by-layer hollow photosensitizer microcapsule design via a manganese carbonate hard template for photodynamic therapy in cells. Photodiagn. Photodyn. Ther. 2018, 22, 169–177. [Google Scholar] [CrossRef]
- Novoselova, M.V.; Voronin, D.V.; Abakumova, T.; Demina, P.; Petrov, A.V.; Petrov, V.V.; Zatsepin, T.; Sukhorukov, G.B.; Gorin, D.A. Focused ultrasound-mediated fluorescence of composite microcapsules loaded with magnetite nanoparticles: In vitro and in vivo study. Colloids Surf. B Biointerfaces 2019, 181, 680–687. [Google Scholar] [CrossRef] [PubMed]
- Pechenkin, M.A.; Möhwald, H.; Volodkin, D.V. pH- and salt-mediated response of layer-by-layer assembled PSS/PAH microcapsules: Fusion and polymer exchange. Soft Matter 2012, 8, 8659–8665. [Google Scholar] [CrossRef]
- Trushina, D.B.; Bukreeva, T.V.; Borodina, T.N.; Belova, D.D.; Belyakov, S.; Antipina, M.N. Heat-driven size reduction of biodegradable polyelectrolyte multilayer hollow capsules assembled on CaCO3 template. Colloids Surf. B Biointerfaces 2018, 170, 312–321. [Google Scholar] [CrossRef] [PubMed]
- Nifontova, G.; Kalenichenko, D.; Baryshnikova, M.; Gomes, F.R.; Alves, F.; Karaulov, A.; Nabiev, I.; Sukhanova, A. Biofunctionalized Polyelectrolyte Microcapsules Encoded with Fluorescent Semiconductor Nanocrystals for Highly Specific Targeting and Imaging of Cancer Cells. Photonics 2019, 6, 117. [Google Scholar] [CrossRef] [Green Version]
- Zan, X.; Garapaty, A.; Champion, J.A. Engineering Polyelectrolyte Capsules with Independently Controlled Size and Shape. Langmuir 2015, 31, 7601–7608. [Google Scholar] [CrossRef] [PubMed]
- Trushina, D.B.; Akasov, R.; Khovankina, A.; Borodina, T.; Bukreeva, T.V.; Markvicheva, E.A. Doxorubicin-loaded biodegradable capsules: Temperature induced shrinking and study of cytotoxicity in vitro. J. Mol. Liq. 2019, 284, 215–224. [Google Scholar] [CrossRef]
- Nifontova, G.; Zvaigzne, M.; Baryshnikova, M.; Korostylev, E.; Ramos-Gomes, F.; Alves, F.; Nabiev, I.; Sukhanova, A. Next-Generation Theranostic Agents Based on Polyelectrolyte Microcapsules Encoded with Semiconductor Nanocrystals: Development and Functional Characterization. Nanoscale Res. Lett. 2018, 13, 30. [Google Scholar] [CrossRef] [Green Version]
- Campbell, J.; Abnett, J.; Kastania, G.; Volodkin, D.; Vikulina, A.S. Which Biopolymers Are Better for the Fabrication of Multilayer Capsules? A Comparative Study Using Vaterite CaCO3 as Templates. ACS Appl. Mater. Interfaces 2021, 13, 3259–3269. [Google Scholar] [CrossRef]
- Novoselova, M.V.; Loh, H.M.; Trushina, D.B.; Ketkar, A.; Abakumova, T.O.; Zatsepin, T.S.; Kakran, M.; Brzozowska, A.M.; Lau, H.H.; Gorin, D.A.; et al. Biodegradable Polymeric Multilayer Capsules for Therapy of Lung Cancer. ACS Appl. Mater. Interfaces 2020, 12, 5610–5623. [Google Scholar] [CrossRef]
- Trushina, D.; Bukreeva, T.V.; Kovalchuk, M.V.; Antipina, M.N. CaCO3 vaterite microparticles for biomedical and personal care applications. Mater. Sci. Eng. C 2014, 45, 644–658. [Google Scholar] [CrossRef] [PubMed]
- Bosio, V.E.; Cacicedo, M.L.; Calvignac, B.; León, I.; Beuvier, T.; Boury, F.; Castro, G.R. Synthesis and characterization of CaCO 3 –biopolymer hybrid nanoporous microparticles for controlled release of doxorubicin. Colloids Surf. B Biointerfaces 2014, 123, 158–169. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Boi, S.; Rouatbi, N.; Dellacasa, E.; Di Lisa, D.; Bianchini, P.; Monticelli, O.; Pastorino, L. Alginate microbeads with internal microvoids for the sustained release of drugs. Int. J. Biol. Macromol. 2020, 156, 454–461. [Google Scholar] [CrossRef] [PubMed]
- Souza, E.F.; Ambrósio, J.A.; Pinto, B.C.; Beltrame, M.; Sakane, K.K.; Pinto, J.G.; Ferreira-Strixino, J.; Gonçalves, E.P.; Simioni, A.R. Vaterite submicron particles designed for photodynamic therapy in cells. Photodiagn. Photodyn. Ther. 2020, 31, 101913. [Google Scholar] [CrossRef]
- Volodkin, D. CaCO3 templated micro-beads and -capsules for bioapplications. Adv. Colloid Interface Sci. 2014, 207, 306–324. [Google Scholar] [CrossRef]
- Svenskaya, Y.; Garello, F.; Lengert, E.; Kozlova, A.; Verkhovskii, R.; Bitonto, V.; Ruggiero, M.R.; German, S.; Gorin, D.; Terreno, E. Biodegradable polyelectrolyte/magnetite capsules for MR imaging and magnetic targeting of tumors. Nanotheranostics 2021, 5, 362–377. [Google Scholar] [CrossRef]
- Zharkov, M.N.; Brodovskaya, E.P.; Kulikov, O.A.; Gromova, E.V.; Ageev, V.P.; Atanova, A.V.; Kozyreva, Z.V.; Tishin, A.M.; Pyatakov, A.P.; Pyataev, N.A.; et al. Enhanced cytotoxicity caused by AC magnetic field for polymer microcapsules containing packed magnetic nanoparticles. Colloids Surf. B Biointerfaces 2020, 199, 111548. [Google Scholar] [CrossRef]
- Nifontova, G.; Krivenkov, V.; Zvaigzne, M.; Samokhvalov, P.S.; Efimov, A.E.; Agapova, O.I.; Agapov, I.I.; Korostylev, E.; Zarubin, S.; Karaulov, A.; et al. Controlling Charge Transfer from Quantum Dots to Polyelectrolyte Layers Extends Prospective Applications of Magneto-Optical Microcapsules. ACS Appl. Mater. Interfaces 2020, 12, 35882–35894. [Google Scholar] [CrossRef]
- Demina, P.A.; Sindeeva, O.A.; Abramova, A.M.; Prikhozhdenko, E.S.; Verkhovskii, R.A.; Lengert, E.V.; Sapelkin, A.V.; Goryacheva, I.Y.; Sukhorukov, G.B. Fluorescent Convertible Capsule Coding Systems for Individual Cell Labeling and Tracking. ACS Appl. Mater. Interfaces 2021, 13, 19701–19709. [Google Scholar] [CrossRef]
- Bilan, R.S.; Krivenkov, V.A.; Berestovoy, M.A.; Efimov, A.E.; Agapov, I.I.; Samokhvalov, P.S.; Nabiev, I.; Sukhanova, A. Engineering of Optically Encoded Microbeads with FRET-Free Spatially Separated Quantum-Dot Layers for Multiplexed Assays. ChemPhysChem 2017, 18, 970–979. [Google Scholar] [CrossRef] [PubMed]
- Ramos-Gomes, F.; Bode, J.; Sukhanova, A.; Bozrova, S.V.; Saccomano, M.; Mitkovski, M.; Krueger, J.E.; Wege, A.K.; Stuehmer, W.; Samokhvalov, P.S.; et al. Single- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dots. Sci. Rep. 2018, 8, 1–12. [Google Scholar] [CrossRef]
- Kage, D.; Hoffmann, K.; Nifontova, G.; Krivenkov, V.; Sukhanova, A.; Nabiev, I.; Resch-Genger, U. Tempo-spectral multiplexing in flow cytometry with lifetime detection using QD-encoded polymer beads. Sci. Rep. 2020, 10, 1–11. [Google Scholar] [CrossRef] [Green Version]
- Romoser, A.; Ritter, D.; Majitha, R.; Meissner, K.E.; McShane, M.; Sayes, C.M. Mitigation of Quantum Dot Cytotoxicity by Microencapsulation. PLoS ONE 2011, 6, e22079. [Google Scholar] [CrossRef] [PubMed]
- Song, D.; Cui, J.; Ju, Y.; Faria, M.; Sun, H.; Howard, C.B.; Thurecht, K.J.; Caruso, F. Cellular Targeting of Bispecific Antibody-Functionalized Poly(ethylene glycol) Capsules: Do Shape and Size Matter? ACS Appl. Mater. Interfaces 2019, 11, 28720–28731. [Google Scholar] [CrossRef]
- Xiong, R.; Hua, D.; Van Hoeck, J.; Berdecka, D.; Léger, L.; De Munter, S.; Fraire, J.C.; Raes, L.; Harizaj, A.; Sauvage, F.; et al. Photothermal nanofibres enable safe engineering of therapeutic cells. Nat. Nanotechnol. 2021, 1–11. [Google Scholar] [CrossRef]
- Timin, A.S.; Lepik, K.V.; Muslimov, A.R.; Gorin, D.A.; Afanasyev, B.V.; Sukhorukov, G.B. Intracellular redox induced drug release in cancerous and mesenchymal stem cells. Colloids Surf. B Biointerfaces 2016, 147, 450–458. [Google Scholar] [CrossRef]
- Ermakov, A.V.; Verkhovskii, R.A.; Babushkina, I.V.; Trushina, D.B.; Inozemtseva, O.A.; Lukyanets, E.A.; Ulyanov, V.J.; Gorin, D.A.; Belyakov, S.; Antipina, M.N. In Vitro Bioeffects of Polyelectrolyte Multilayer Microcapsules Post-Loaded with Water-Soluble Cationic Photosensitizer. Pharmaceutics 2020, 12, 610. [Google Scholar] [CrossRef]
- Carvalho, C.; Santos, R.X.; Cardoso, S.; Correia, S.; Oliveira, P.J.; Santos, M.S.; Moreira, P.I. Doxorubicin: The Good, the Bad and the Ugly Effect. Curr. Med. Chem. 2009, 16, 3267–3285. [Google Scholar] [CrossRef]
- Mohan, P.; Rapoport, N. Doxorubicin as a Molecular Nanotheranostic Agent: Effect of Doxorubicin Encapsulation in Micelles or Nanoemulsions on the Ultrasound-Mediated Intracellular Delivery and Nuclear Trafficking. Mol. Pharm. 2010, 7, 1959–1973. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tewes, F.; Munnier, E.; Antoon, B.; Okassa, L.N.; Cohen-Jonathan, S.; Marchais, H.; Douziech-Eyrolles, L.; Soucé, M.; Dubois, P.; Chourpa, I. Comparative study of doxorubicin-loaded poly(lactide-co-glycolide) nanoparticles prepared by single and double emulsion methods. Eur. J. Pharm. Biopharm. 2007, 66, 488–492. [Google Scholar] [CrossRef] [PubMed]
- Nifontova, G.; Efimov, A.; Agapova, O.; Agapov, I.; Nabiev, I.; Sukhanova, A. Bioimaging Tools Based on Polyelectrolyte Microcapsules Encoded with Fluorescent Semiconductor Nanoparticles: Design and Characterization of the Fluorescent Properties. Nanoscale Res. Lett. 2019, 14, 29. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lu, Z.; Zhang, J.; Ma, Y.; Song, S.; Gu, W. Biomimetic mineralization of calcium carbonate/carboxymethylcellulose microspheres for lysozyme immobilization. Mater. Sci. Eng. C 2012, 32, 1982–1987. [Google Scholar] [CrossRef]
- Vikulina, A.; Webster, J.; Voronin, D.; Ivanov, E.; Fakhrullin, R.; Vinokurov, V.; Volodkin, D. Mesoporous additive-free vaterite CaCO3 crystals of untypical sizes: From submicron to Giant. Mater. Des. 2020, 197, 109220. [Google Scholar] [CrossRef]
- Musin, E.V.; Kim, A.L.; Tikhonenko, S.A. Destruction of Polyelectrolyte Microcapsules Formed on CaCO3 Microparticles and the Release of a Protein Included by the Adsorption Method. Polymers 2020, 12, 520. [Google Scholar] [CrossRef] [Green Version]
- Bilan, R.; Fleury, F.; Nabiev, I.; Sukhanova, A. Quantum Dot Surface Chemistry and Functionalization for Cell Targeting and Imaging. Bioconjugate Chem. 2015, 26, 609–624. [Google Scholar] [CrossRef]
- Musin, E.V.; Kim, A.L.; Dubrovskii, A.V.; Tikhonenko, S.A. New sight at the organization of layers of multilayer polyelectrolyte microcapsules. Sci. Rep. 2021, 11, 1–7. [Google Scholar] [CrossRef]
- Tao, X.; Chen, H.; Sun, X.-J.; Chen, J.-F.; Roa, W.H. Formulation and cytotoxicity of doxorubicin loaded in self-assembled bio-polyelectrolyte microshells. Int. J. Pharm. 2007, 336, 376–381. [Google Scholar] [CrossRef] [PubMed]
- Zhao, Q.; Han, B.; Wang, Z.; Gao, C.; Peng, C.; Shen, J. Hollow chitosan-alginate multilayer microcapsules as drug delivery vehicle: Doxorubicin loading and in vitro and in vivo studies. Nanomed. Nanotechnol. Biol. Med. 2007, 3, 63–74. [Google Scholar] [CrossRef] [PubMed]
- Sudareva, N.; Suvorova, O.; Saprykina, N.; Vlasova, H.; Vilesov, A. Doxorubicin delivery systems based on doped CaCO3 cores and polyanion drug conjugates. J. Microencapsul. 2021, 38, 164–176. [Google Scholar] [CrossRef] [PubMed]
- Balabushevich, N.G.; Kovalenko, E.A.; Le-Deygen, I.M.; Filatova, L.Y.; Volodkin, D.; Vikulina, A.S. Hybrid CaCO3-mucin crystals: Effective approach for loading and controlled release of cationic drugs. Mater. Des. 2019, 182, 108020. [Google Scholar] [CrossRef]
Sample * | Size, µm ** | ζ-Potential, mV |
---|---|---|
DOX-free MBs | 2.5 ± 07 | −17.2 ± 0.8 |
DOX-free MCs | 2.0 ± 0.4 | −20.4 ± 2.2 |
DOX-containing MBs | 2.0 ± 0.4 | −12.5 ± 1.7 |
DOX-containing MCs(8L) | 2.4 ± 0.6 | −7.5 ± 2.2 |
DOX-containing MBs(+8L) | 2.0 ± 0.8 | −23.5 ± 2.4 |
Component * | Size, nm ** | ζ-Potential, mV |
---|---|---|
PAH | 13.9 ± 0.2 | +15.9 ± 2.4 |
PSS | 32.5 ± 2.8 | −18.6 ± 1.9 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kalenichenko, D.; Nifontova, G.; Karaulov, A.; Sukhanova, A.; Nabiev, I. Designing Functionalized Polyelectrolyte Microcapsules for Cancer Treatment. Nanomaterials 2021, 11, 3055. https://doi.org/10.3390/nano11113055
Kalenichenko D, Nifontova G, Karaulov A, Sukhanova A, Nabiev I. Designing Functionalized Polyelectrolyte Microcapsules for Cancer Treatment. Nanomaterials. 2021; 11(11):3055. https://doi.org/10.3390/nano11113055
Chicago/Turabian StyleKalenichenko, Daria, Galina Nifontova, Alexander Karaulov, Alyona Sukhanova, and Igor Nabiev. 2021. "Designing Functionalized Polyelectrolyte Microcapsules for Cancer Treatment" Nanomaterials 11, no. 11: 3055. https://doi.org/10.3390/nano11113055