Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

ConA-Coated Liposomes as a System to Delivery β-Lapachone to Breast Cancer Cells

Author(s): Larissa Franca, Milena Ferraz, Maria Clara Barros, Victor Gibson, Francisco Humberto Xavier-Júnior, Nereide Stela Santos Magalhães* and Mariane Lira-Nogueira*

Volume 22, Issue 5, 2022

Published on: 03 January, 2022

Page: [968 - 977] Pages: 10

DOI: 10.2174/1871520621666210624112452

Price: $65

Abstract

Background: Target treatment using site-specific nanosystems is a hot topic for treating several diseases, especially cancer.

Objective: The study was set out to develop site-specific liposomes using ConcanavalinA (ConA) to target β- lapachone(β-lap) to human breast cancer cells.

Methods: Liposomes were prepared and characterized according to diameter size, zeta potential, ConA conjugation(%) and β-lap encapsulation efficiency (%). Isothermal Titration Calorimetry evaluated the binding energy between the biomolecules, which compose of the liposomes. ConA avidity was assessed before and after conjugation. Cytotoxicity was evaluated, and fluorescence microscopy was performed to investigate the influence of ConA influenced on MCF-7 uptake.

Results: Uncoated and ConA-coated liposomes presented size, and zeta potential values from 97.46 ± 2.01 to 152.23 ± 2.73 nm, and -6.83 ± 0.28 to -17.23 ±0.64 mV, respectively. Both ConA conjugation and β-lap encapsulation efficiency were approximately 100%. The favorable and spontaneous process confirmed the binding between ConA and the lipid. Hemagglutination assay confirmed ConA avidity once Lipo-ConA and Lipo-PEG-ConA were able to hemagglutinate the red blood cells at 128-1 and 256-1, respectively. Lipo-ConA was not cytotoxic, and the site-specific liposomes presented the highest toxicity. ConA-coated liposomes were more internalized by MCF7 than uncoated-liposomes.

Conclusion: Therefore, the presence of ConA on the surface of liposomes influenced MCF7 uptake, in that way could be used as a promising site-specific system to target β-lap to cancer cells.

Keywords: Nanosystems, liposomes, β-lapachone, Concanavalin A, ITC, MCF7 cells.

« Previous Next »
Graphical Abstract

[1]
Stewart, B.W.; Wild, C.P. World Cancer Report 2014; Organization, W.H., Ed.; International agency for research on cancer,WHO: Lyon. , 2014.
[2]
Parhi, P.; Mohanty, C.; Sahoo, S.K. Nanotechnology-based combinational drug delivery: An emerging approach for cancer therapy. Drug Discov. Today, 2012, 17(17-18), 1044-1052.
[http://dx.doi.org/10.1016/j.drudis.2012.05.010] [PMID: 22652342]
[3]
Turek, M.; Krzyczmonik, M.; Balczewski, P. New hopes in cancer battle - a review of new molecules and treatment strategies. Med. Chem., 2016, 12(8), 700-719.
[http://dx.doi.org/10.2174/1573406412666160502153700] [PMID: 27140184]
[4]
Moreno, E.; Schwartz, J.; Larrea, E.; Conde, I.; Font, M.; Sanmartín, C.; Irache, J.M.; Espuelas, S. Assessment of β-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in L. major infected BALB/c mice. Nanomedicine (Lond.), 2015, 11(8), 2003-2012.
[http://dx.doi.org/10.1016/j.nano.2015.07.011] [PMID: 26282379]
[5]
Cavalcanti, I.M.F.; Pontes-Neto, J.G.; Kocerginsky, P.O.; Bezerra-Neto, A.M.; Lima, J.L.C.; Lira-Nogueira, M.C.B.; Maciel, M.A.V.; Neves, R.P.; Pimentel, M.F.; Santos-Magalhães, N.S. Antimicrobial activity of β-lapachone encapsulated into liposomes against meticillin-resistant Staphylococcus aureus and Cryptococcus neoformans clinical strains. J. Glob. Antimicrob. Resist., 2015, 3(2), 103-108.
[http://dx.doi.org/10.1016/j.jgar.2015.03.007] [PMID: 27873657]
[6]
Aires, Ade. L. Ximenes, E.C.P.A.; Barbosa, V.X.; Góes, A.J.S.; Souza, V.M.O.; Albuquerque, M.C.P.A. β-Lapachone: A naphthoquinone with promising antischistosomal properties in mice. Phytomedicine, 2014, 21(3), 261-267.
[http://dx.doi.org/10.1016/j.phymed.2013.08.012] [PMID: 24090700]
[7]
Medeiros, C.S.; Pontes-Filho, N.T.; Camara, C.A.; Lima-Filho, J.V.; Oliveira, P.C.; Lemos, S.A.; Leal, A.F.G.; Brandão, J.O.C.; Neves, R.P. Antifungal activity of the naphthoquinone beta-lapachone against disseminated infection with Cryptococcus neoformans var. neoformans in dexamethasone-immunosuppressed Swiss mice. Braz. J. Med. Biol. Res., 2010, 43(4), 345-349.
[http://dx.doi.org/10.1590/S0100-879X2010007500012] [PMID: 20209378]
[8]
Sharma, P.; Wollenberg, K.; Sellers, M.; Zainabadi, K.; Galinsky, K.; Moss, E.; Nguitragool, W.; Neafsey, D.; Desai, S.A. An epigenetic antimalarial resistance mechanism involving parasite genes linked to nutrient uptake. J. Biol. Chem., 2013, 288(27), 19429-19440.
[http://dx.doi.org/10.1074/jbc.M113.468371] [PMID: 23720749]
[9]
Guimarães, T.T. Pinto, Mdo.C.; Lanza, J.S.; Melo, M.N.; do Monte-Neto, R.L.; de Melo, I.M.M.; Diogo, E.B.T.; Ferreira, V.F.; Camara, C.A.; Valença, W.O.; de Oliveira, R.N.; Frézard, F.; da Silva, E.N., Jr Potent naphthoquinones against antimony-sensitive and -resistant Leishmania parasites: Synthesis of novel α- and nor-α-lapachone-based 1,2,3-triazoles by copper-catalyzed azide-alkyne cycloaddition. Eur. J. Med. Chem., 2013, 63, 523-530.
[http://dx.doi.org/10.1016/j.ejmech.2013.02.038] [PMID: 23535320]
[10]
Kung, H.N.; Weng, T.Y.; Liu, Y.L.; Lu, K.S.; Chau, Y.P. Sulindac compounds facilitate the cytotoxicity of β-lapachone by up-regulation of NAD(P)H quinone oxidoreductase in human lung cancer cells. PLoS One, 2014, 9(2), e88122.
[http://dx.doi.org/10.1371/journal.pone.0088122] [PMID: 24505400]
[11]
Li, W.W.; Yu, J.Y.; Xu, H.L.; Bao, J.K.; Concanavalin, A.; Concanavalin, A. A potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics. Biochem. Biophys. Res. Commun., 2011, 414(2), 282-286.
[http://dx.doi.org/10.1016/j.bbrc.2011.09.072] [PMID: 21951850]
[12]
Lamberti, M.J.; Vittar, N.B. da Silva, Fde.C.; Ferreira, V.F.; Rivarola, V.A. Synergistic enhancement of antitumor effect of β-Lapachone by photodynamic induction of quinone oxidoreductase (NQO1). Phytomedicine, 2013, 20(11), 1007-1012.
[http://dx.doi.org/10.1016/j.phymed.2013.04.018] [PMID: 23746950]
[13]
Yu, H.Y.; Kim, S.O.; Jin, C.Y.; Kim, G-Y.; Kim, W.J.; Yoo, Y.H.; Choi, Y.H. β-lapachone-induced apoptosis of human gastric carcinoma ags cells is caspase-dependent and regulated by the pi3k/akt pathway. Biomol. Ther. (Seoul), 2014, 22(3), 184-192.
[http://dx.doi.org/10.4062/biomolther.2014.026] [PMID: 25009698]
[14]
de Almeida, E.R.; Lucena, F.R.S.; Silva, C.V.N.S.; da Silva Costa-Junior, W.; Cavalcanti, J.B.; Couto, G.B.L.; da Silva, L.L.; da Mota, D.L.; da Silveira, A.B.; de Sousa Filho, S.D.; da Silva, A.C. Toxicological assessment of beta-lapachone on organs from pregnant and non-pregnant rats. Phytother. Res., 2009, 23(9), 1276-1280.
[http://dx.doi.org/10.1002/ptr.2646] [PMID: 19197915]
[15]
Xavier-Junior, F.H.; Rabello, M.M.; Hernandes, M.Z.; Dias, M.E.S.; Andrada, O.H.M.S.; Bezerra, B.P.; Ayala, A.P.; Santos-Magalhães, N.S. Supramolecular interactions between β-lapachone with cyclodextrins studied using isothermal titration calorimetry and molecular modeling. J. Mol. Recognit., 2017, 30(11), 1-10.
[http://dx.doi.org/10.1002/jmr.2646] [PMID: 28675505]
[16]
Cavalcanti, I.M.F.; Mendonça, E.A.; Lira, M.C.; Honrato, S.B.; Camara, C.A.; Amorim, R.V.; Mendes Filho, J.; Rabello, M.M.; Hernandes, M.Z.; Ayala, A.P.; Santos-Magalhães, N.S. The encapsulation of β-lapachone in 2-hydroxypropyl-β-cyclodextrin inclusion complex into liposomes: A physicochemical evaluation and molecular modeling approach. Eur. J. Pharm. Sci., 2011, 44(3), 332-340.
[http://dx.doi.org/10.1016/j.ejps.2011.08.011] [PMID: 21888967]
[17]
Nakamura, H.; Fang, J.; Maeda, H. Development of next-generation macromolecular drugs based on the EPR effect: Challenges and pitfalls. Expert Opin. Drug Deliv., 2015, 12(1), 53-64.
[http://dx.doi.org/10.1517/17425247.2014.955011] [PMID: 25425260]
[18]
Costa, L.C.; Souza, B.N.; Almeida, F.F.; Lagranha, C.J.; Cadena, P.G.; Santos-Magalhães, N.S.; Lira-Nogueira, M.C. Glutamine-loaded liposomes: Preliminary investigation, characterization, and evaluation of neutrophil viability. AAPS PharmSciTech, 2016, 17(2), 446-453.
[http://dx.doi.org/10.1208/s12249-015-0375-0] [PMID: 26228746]
[19]
Allen, T.M.; Cullis, P.R. Liposomal drug delivery systems: From concept to clinical applications. Adv. Drug Deliv. Rev., 2013, 65(1), 36-48.
[http://dx.doi.org/10.1016/j.addr.2012.09.037] [PMID: 23036225]
[20]
Mauceri, A.; Borocci, S.; Galantini, L.; Giansanti, L.; Mancini, G.; Martino, A.; Salvati Manni, L.; Sperduto, C. Recognition of concanavalin A by cationic glucosylated liposomes. Langmuir, 2014, 30(38), 11301-11306.
[http://dx.doi.org/10.1021/la502946t] [PMID: 25185719]
[21]
Sharon, N.; Lis, H. History of lectins: From hemagglutinins to biological recognition molecules. Glycobiology, 2004, 14(11), 53R-62R.
[http://dx.doi.org/10.1093/glycob/cwh122] [PMID: 15229195]
[22]
Li, C-Y.; Xu, H-L.; Liu, B.; Bao, J-K. Concanavalin A, from an old protein to novel candidate anti-neoplastic drug. Curr. Mol. Pharmacol., 2010, 3(3), 123-128.
[http://dx.doi.org/10.2174/1874467211003030123] [PMID: 20533895]
[23]
Hannigan, A.M.; Gorski, S.M. Macroautophagy: The key ingredient to a healthy diet? Autophagy, 2009, 5(2), 140-151.
[http://dx.doi.org/10.4161/auto.5.2.7529] [PMID: 19098459]
[24]
Ruhul Amin, A.R.; Oo, M.L.; Senga, T.; Suzuki, N.; Feng, G.S.; Hamaguchi, M. SH2 domain containing protein tyrosine phosphatase 2 regulates concanavalin A-dependent secretion and activation of matrix metalloproteinase 2 via the extracellular signal-regulated kinase and p38 pathways. Cancer Res., 2003, 63(19), 6334-6339.
[PMID: 14559821]
[25]
Sina, A.; Proulx-Bonneau, S.; Roy, A.; Poliquin, L.; Cao, J.; Annabi, B. The lectin concanavalin-a signals MT1-MMP catalytic independent induction of COX-2 through an IKKgamma/NF-kappaB-dependent pathway. J. Cell Commun. Signal., 2010, 4(1), 31-38.
[http://dx.doi.org/10.1007/s12079-009-0084-0] [PMID: 20195390]
[26]
Lira, M.C.B.; Ferraz, M.S.; Silva, D.G.V.C.; Cortes, M.E.; Teixeira, K.I.; Caetano, N.P.; Sinisterra, R.D.; Ponchel, G.; Santos-Magalhães, N.S. Inclusion complex of usnic acid with β-cyclodextrin: Characterization and nanoencapsulation into liposomes. J. Incl. Phenom. Macrocycl. Chem., 2009, 64(3–4), 215-224.
[http://dx.doi.org/10.1007/s10847-009-9554-5]
[27]
Santos, H.M.L.R.; Queiroz, F.B.; Maior, R.M.S.; Nascimento, S.C.; Santos-Magalhães, N.S. Cytotoxicity of doxorubicin-loaded con a-liposomes. Drug Dev. Res., 2006, 67, 430-437.
[http://dx.doi.org/10.1002/ddr.20091]
[28]
Bakowsky, H.; Richter, T.; Kneuer, C.; Hoekstra, D.; Rothe, U.; Bendas, G.; Ehrhardt, C.; Bakowsky, U. Adhesion characteristics and stability assessment of lectin-modified liposomes for site-specific drug delivery. Biochim. Biophys. Acta, 2008, 1778(1), 242-249.
[http://dx.doi.org/10.1016/j.bbamem.2007.09.033] [PMID: 17964278]
[29]
Peterson, G.L. A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal. Biochem., 1977, 83(2), 346-356.
[http://dx.doi.org/10.1016/0003-2697(77)90043-4] [PMID: 603028]
[30]
Cunha-Filho, M.S.S.; Alves, F.C.; Alves, M.G.C.; Monteiro, D.B.; Medeiros, M.F.P.; Neto, P.J.R. Beta-lapachone: Development and validation of analytical method for new therapeutic antineoplastic alternative. Rev. Bras. Farm., 2005, 86(1), 39-43.
[31]
Kizhakkedathu, J.N.; Creagh, A.L.; Shenoi, R.A.; Rossi, N.A.A.; Brooks, D.E.; Chan, T.; Lam, J.; Dandepally, S.R.; Haynes, C.A. High molecular weight polyglycerol-based multivalent mannose conjugates. Biomacromolecules, 2010, 11(10), 2567-2575.
[http://dx.doi.org/10.1021/bm1004788] [PMID: 20804173]
[32]
Alley, M.C.; Scudiero, D.A.; Monks, A.; Hursey, M.L.; Czerwinski, M.J.; Fine, D.L.; Abbott, B.J.; Mayo, J.G.; Shoemaker, R.H.; Boyd, M.R. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res., 1988, 48(3), 589-601.
[PMID: 3335022]
[33]
Khan, D.R.; Webb, M.N.; Cadotte, T.H.; Gavette, M.N. Use of targeted liposome-based chemotherapeutics to treat breast cancer. Breast Cancer (Auckl.), 2015, 9(Suppl. 2), 1-5.
[http://dx.doi.org/10.4137/BCBCR.S29421] [PMID: 26309409]
[34]
Sarup, J.; Jin, P.; Turin, L.; Bai, X.; Beryt, M.; Brdlik, C.; Higaki, J.N.; Jorgensen, B.; Lau, F.W.; Lindley, P.; Liu, J.; Ni, I.; Rozzelle, J.; Kumari, R.; Watson, S.A.; Zhang, J.; Shepard, H.M. Human epidermal growth factor receptor (HER-1:HER-3) Fc-mediated heterodimer has broad antiproliferative activity in vitro and in human tumor xenografts. Mol. Cancer Ther., 2008, 7(10), 3223-3236.
[http://dx.doi.org/10.1158/1535-7163.MCT-07-2151] [PMID: 18852126]
[35]
Bendas, G.; Rothe, U.; Scherphof, G.L.; Kamps, J.A.A.M. The influence of repeated injections on pharmacokinetics and biodistribution of different types of sterically stabilized immunoliposomes. Biochim. Biophys. Acta, 2003, 1609(1), 63-70.
[http://dx.doi.org/10.1016/S0005-2736(02)00655-7] [PMID: 12507759]
[36]
Lee, H.Y.; Mohammed, K.A.; Kaye, F.; Sharma, P.; Moudgil, B.M.; Clapp, W.L.; Nasreen, N. Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer. Int. J. Nanomedicine, 2013, 8, 4481-4494.
[http://dx.doi.org/10.2147/IJN.S41782] [PMID: 24293999]
[37]
Bendas, G.; Krause, A.; Bakowsky, U.; Vogel, J.; Rothe, U. Targetability of novel immunoliposomes prepared by a new antibody conjugation technique. Int. J. Pharm., 1999, 181(1), 79-93.
[http://dx.doi.org/10.1016/S0378-5173(99)00002-2] [PMID: 10370205]
[38]
Chmielewski, M.J.; Buhler, E.; Candau, J.; Lehn, J.M. Multivalency by self-assembly: Binding of concanavalin A to metallosupramolecular architectures decorated with multiple carbohydrate groups. Chemistry, 2014, 20(23), 6960-6977.
[http://dx.doi.org/10.1002/chem.201304511] [PMID: 24764182]
[39]
Francis, S.E.; Hutchinson, F.J.; Lyle, I.G.; Jones, M.N. The control of protein surface concentration on proteoliposomes. Colloids Surf., 1992, 62(1–2), 163-176.
[http://dx.doi.org/10.1016/0166-6622(92)80049-8]
[40]
Cunha-Filho, M.S.S.; Martínez-Pacheco, R.; Landin, M. Effect of storage conditions on the stability of β-lapachone in solid state and in solution. J. Pharm. Pharmacol., 2013, 65(6), 798-806.
[http://dx.doi.org/10.1111/jphp.12040] [PMID: 23647673]
[41]
Sharon, N.; Lis, H. Lectins: Cell-agglutinating and sugar-specific proteins. Science (80-. ), 1972, 177(4053), 949-959.
[42]
Lis, H.; Sharon, N. Lectins: Carbohydrate-specific proteins that mediate cellular recognition. Chem. Rev., 1998, 98(2), 637-674.
[http://dx.doi.org/10.1021/cr940413g] [PMID: 11848911]
[43]
Camaleño de la Calle, A.; Gerke, C.; Chang, X.J.; Grafmüller, A.; Hartmann, L.; Schmidt, S. Multivalent interactions of polyamide based sequence-controlled glycomacromolecules with concanavalin A. Macromol. Biosci., 2019, 19(6)e1900033
[http://dx.doi.org/10.1002/mabi.201900033] [PMID: 30977977]
[44]
Dam, T.K.; Roy, R.; Das, S.K.; Oscarson, S.; Brewer, C.F. Binding of multivalent carbohydrates to concanavalin A and Dioclea grandiflora lectin. Thermodynamic analysis of the “multivalency effect”. J. Biol. Chem., 2000, 275(19), 14223-14230.
[http://dx.doi.org/10.1074/jbc.275.19.14223] [PMID: 10799500]
[45]
Mandal, D.K.; Kishore, N.; Brewer, C.F. Thermodynamics of lectin-carbohydrate interactions. Titration microcalorimetry measurements of the binding of N-linked carbohydrates and ovalbumin to concanavalin A. Biochemistry, 1994, 33(5), 1149-1156.
[http://dx.doi.org/10.1021/bi00171a014] [PMID: 8110746]
[46]
Naismith, J.H.; Emmerich, C.; Habash, J.; Harrop, S.J.; Helliwell, J.R.; Hunter, W.N.; Raftery, J.; Kalb, A.J.; Yariv, J. Refined structure of concanavalin A complexed with methyl alpha-D-mannopyranoside at 2.0 A resolution and comparison with the saccharide-free structure. Acta Crystallogr. D Biol. Crystallogr., 1994, 50(Pt 6), 847-858.
[http://dx.doi.org/10.1107/S0907444994005287] [PMID: 15299352]
[47]
Bendas, G.; Vogel, J.; Bakowski, U.; Krause, A.; Müller, J.; Rothe, U. A liposome-based model system for the simulation of lectin-induced cell adhesion. Biochim. Biophys. Acta, 1997, 1325(2), 297-308.
[http://dx.doi.org/10.1016/S0005-2736(96)00268-4] [PMID: 9168155]
[48]
Freire, E. Do enthalpy and entropy distinguish first in class from best in class? Drug Discov. Today, 2008, 13(19-20), 869-874.
[http://dx.doi.org/10.1016/j.drudis.2008.07.005] [PMID: 18703160]
[49]
Du, X.; Li, Y.; Xia, Y-L.; Ai, S-M.; Liang, J.; Sang, P.; Ji, X-L.; Liu, S-Q. Insights into protein-ligand interactions: Mechanisms, models, and methods. Int. J. Mol. Sci., 2016, 17(2), 144.
[http://dx.doi.org/10.3390/ijms17020144] [PMID: 26821017]
[50]
Huang, R.; Lau, B.L.T. Biomolecule-nanoparticle interactions: Elucidation of the thermodynamics by isothermal titration calorimetry. Biochim. Biophys. Acta, 2016, 1860(5), 945-956.
[http://dx.doi.org/10.1016/j.bbagen.2016.01.027] [PMID: 26851677]
[51]
Gilson, M.K.; Zhou, H-X. Calculation of protein-ligand binding affinities. Annu. Rev. Biophys. Biomol. Struct., 2007, 36, 21-42.
[http://dx.doi.org/10.1146/annurev.biophys.36.040306.132550] [PMID: 17201676]

Rights & Permissions Print Cite
Article Metrics
20
1
© 2024 Bentham Science Publishers | Privacy Policy