Carbon Dots-Biomembrane Interactions and Their Implications for Cellular Drug Delivery

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2023 Jun 28

PMID 37375780

Authors

Barbara Mavroidi

Archontia Kaminari

Elias Sakellis

Zili Sideratou

Dimitris Tsiourvas

Affiliations

Soon will be listed here.

Abstract

The effect of carbon dots (CDs) on a model blayer membrane was studied as a means of comprehending their ability to affect cell membranes. Initially, the interaction of N-doped carbon dots with a biophysical liposomal cell membrane model was investigated by dynamic light scattering, z-potential, temperature-modulated differential scanning calorimetry, and membrane permeability. CDs with a slightly positive charge interacted with the surface of the negative-charged liposomes and evidence indicated that the association of CDs with the membrane affects the structural and thermodynamic properties of the bilayer; most importantly, it enhances the bilayer's permeability against doxorubicin, a well-known anticancer drug. The results, like those of similar studies that surveyed the interaction of proteins with lipid membranes, suggest that carbon dots are partially embedded in the bilayer. In vitro experiments employing breast cancer cell lines and human healthy dermal cells corroborated the findings, as it was shown that the presence of CDs in the culture medium selectively enhanced cell internalization of doxorubicin and, subsequently, increased its cytotoxicity, acting as a drug sensitizer.

References

Eleftheriou K, Sideratou Z, Thanassoulas A, Papakyriakou A, Tsiourvas D . Comparative Experimental and Computational Study of Monoalkyl Chain Phosphatidylcholine-Containing Thermoresponsive Liposomes. J Phys Chem B. 2016; 120(24):5417-28. DOI: 10.1021/acs.jpcb.6b02783. View

De S, Maity A, Bagchi D, Chakraborty A . Lipid phase dependent distinct emission behaviour of hydrophobic carbon dots: C-dot based membrane probes. Chem Commun (Camb). 2021; 57(72):9080-9083. DOI: 10.1039/d1cc01941d. View

Garcia-Saez A, Schwille P . Stability of lipid domains. FEBS Lett. 2009; 584(9):1653-8. DOI: 10.1016/j.febslet.2009.12.036. View

Yan G, Song Z, Liu Y, Su Q, Liang W, Cao A . Effects of carbon dots surface functionalities on cellular behaviors - Mechanistic exploration for opportunities in manipulating uptake and translocation. Colloids Surf B Biointerfaces. 2019; 181:48-57. DOI: 10.1016/j.colsurfb.2019.05.027. View

Ipsen J, Mouritsen O . Modelling the phase equilibria in two-component membranes of phospholipids with different acyl-chain lengths. Biochim Biophys Acta. 1988; 944(2):121-34. DOI: 10.1016/0005-2736(88)90425-7. View

Garidel P, Blume A . Miscibility of phospholipids with identical headgroups and acyl chain lengths differing by two methylene units: effects of headgroup structure and headgroup charge. Biochim Biophys Acta. 1998; 1371(1):83-95. DOI: 10.1016/s0005-2736(98)00005-4. View

Mailander V, Landfester K . Interaction of nanoparticles with cells. Biomacromolecules. 2009; 10(9):2379-400. DOI: 10.1021/bm900266r. View

Leal C, Rognvaldsson S, Fossheim S, Nilssen E, Topgaard D . Dynamic and structural aspects of PEGylated liposomes monitored by NMR. J Colloid Interface Sci. 2008; 325(2):485-93. DOI: 10.1016/j.jcis.2008.05.051. View

Tagami T, Ernsting M, Li S . Efficient tumor regression by a single and low dose treatment with a novel and enhanced formulation of thermosensitive liposomal doxorubicin. J Control Release. 2011; 152(2):303-9. DOI: 10.1016/j.jconrel.2011.02.009. View

10.

Nandi S, Malishev R, Bhunia S, Kolusheva S, Jopp J, Jelinek R . Lipid-Bilayer Dynamics Probed by a Carbon Dot-Phospholipid Conjugate. Biophys J. 2016; 110(9):2016-25. PMC: 4939762. DOI: 10.1016/j.bpj.2016.04.005. View

11.

Bornemann S, Herzog M, Winter R . Impact of Y-ions on the structure and phase behavior of phospholipid model membranes. Phys Chem Chem Phys. 2019; 21(10):5730-5743. DOI: 10.1039/c8cp07413e. View

12.

Wang B, Zhang L, Bae S, Granick S . Nanoparticle-induced surface reconstruction of phospholipid membranes. Proc Natl Acad Sci U S A. 2008; 105(47):18171-5. PMC: 2587577. DOI: 10.1073/pnas.0807296105. View

13.

Zhu S, Meng Q, Wang L, Zhang J, Song Y, Jin H . Highly photoluminescent carbon dots for multicolor patterning, sensors, and bioimaging. Angew Chem Int Ed Engl. 2013; 52(14):3953-7. DOI: 10.1002/anie.201300519. View

14.

Papahadjopoulos D, Moscarello M, Eylar E, Isac T . Effects of proteins on thermotropic phase transitions of phospholipid membranes. Biochim Biophys Acta. 1975; 401(3):317-35. DOI: 10.1016/0005-2736(75)90233-3. View

15.

Jaaskelainen I, Monkkonen J, Urtti A . Oligonucleotide-cationic liposome interactions. A physicochemical study. Biochim Biophys Acta. 1994; 1195(1):115-23. DOI: 10.1016/0005-2736(94)90017-5. View

16.

Verma A, Stellacci F . Effect of surface properties on nanoparticle-cell interactions. Small. 2009; 6(1):12-21. DOI: 10.1002/smll.200901158. View

17.

Kuo T, Sung S, Hsu C, Chang C, Chiu T, Hu C . One-pot green hydrothermal synthesis of fluorescent nitrogen-doped carbon nanodots for in vivo bioimaging. Anal Bioanal Chem. 2015; 408(1):77-82. DOI: 10.1007/s00216-015-9138-8. View

18.

Ding H, Ma Y . Theoretical and computational investigations of nanoparticle-biomembrane interactions in cellular delivery. Small. 2014; 11(9-10):1055-71. DOI: 10.1002/smll.201401943. View

19.

Lim S, Shen W, Gao Z . Carbon quantum dots and their applications. Chem Soc Rev. 2014; 44(1):362-81. DOI: 10.1039/c4cs00269e. View

20.

Siepmann J, Peppas N . Higuchi equation: derivation, applications, use and misuse. Int J Pharm. 2011; 418(1):6-12. DOI: 10.1016/j.ijpharm.2011.03.051. View