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Current Nanoscience

Editor-in-Chief

ISSN (Print): 1573-4137
ISSN (Online): 1875-6786

Research Article

Chitosan Nanoparticles Plus KLH Adjuvant as an Alternative for Human Dendritic Cell Differentiation

Author(s): Moisés Armides Franco-Molina*, Erika Evangelina Coronado-Cerda, Edgar López-Pacheco, Diana Ginette Zarate-Triviño, Sergio Arturo Galindo-Rodríguez, Maria del Carmén Salazar-Rodríguez, Yareellys Ramos-Zayas, Reyes Tamez-Guerra and Cristina Rodríguez-Padilla

Volume 15, Issue 5, 2019

Page: [532 - 540] Pages: 9

DOI: 10.2174/1573413714666181008110627

open access plus

Abstract

Background: Immunotherapy involving dendritic cells (DC) has been used to treat cancer with satisfactory results. The generation of mature dendritic cells derived from monocytes, however, is expensive because of the use of cytokines.

Objective: To reduce DC therapy costs, it is important to evaluate lower-cost materials capable of inducing dendritic cell maturation; for this purpose, we synthetized chitosan nanoparticles.

Methods: Chitosan nanoparticles were synthetized by ionic gelation and characterized using dynamic light scattering, laser Doppler electrophoresis, transmission electron microscopy and infrared spectrum. Endotoxin levels were determined by Limulus amoebocyte lysate. The biological effect was evaluated by microscopy, immunophenotypification, cellular viability and phagocytosis assays.

Results: We synthetized endotoxin-free chitosan nanoparticles with an average size of 208 nm and semi-spherical morphology. The nanoparticles induced changes in monocyte morphology, surface marker expression and phagocytosis that correlate with those of DC. These preliminary results demonstrate that chitosan nanoparticles can induce monocyte differentiation into immature dendritic cells and, when combined with albumin and keyhole limpet hemocyanin, they can induce dendritic cell maturation.

Conclusion: We conclude that chitosan nanoparticles are a suitable alternative for lower-cost DC immunotherapy generation, provided that our results be corroborated in vivo.

Keywords: Chitosan, nanoparticles, differentiation, dendritic cells, immunotherapy, cytokines.

Graphical Abstract
[1]
Merad, M.; Sathe, P.; Helft, J.; Miller, J.; Mortha, A. The dendritic cell lineage: Ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu. Rev. Immunol., 2013, 31, 563-604.
[2]
Tang, L.; Zhang, Z.; Zheng, J.; Sheng, J.; Liu, K. Phenotypic and functional characteristics of dendritic cells derived from human peripheral blood monocytes. J. Zhejiang Univ. Sci. 2005, B 6, 1176-1181.
[3]
Collin, M.; McGovern, N.; Haniffa, M. Human dendritic cell subsets. Immunology, 2013, 140, 22-30.
[4]
Gustafson, M.; Lin, Y.; Maas, M.; Van Keulen, V.; Johnston, P.; Peikert, T.; Gastineau, D.; Dietz, A. A method for identification and analysis of non-overlapping myeloid immunophenotypes in humans. PLoS One, 2015, 10(3), 1-19.
[5]
Van de Laar, L.; Coffer, P.; Woltman, A. Regulation of dendritic cell development by GM-CSF: Molecular control and implications for immune homeostasis and therapy. Blood, 2012, 119, 3383-3393.
[6]
Bhattacharya, P.; Haddad, C.; Alharshawi, K.; Prabhakar, B. The role of GM-CSF in dendritic cell development in vivo (HEM3P.284). J. Immunol., 2014, 192, 51-64.
[7]
Lo, J.; Xia, C.; Peng, R.; Clare-Salzler, M. Immature dendritic cell therapy confers durable immune modulation in an antigen-dependent and antigen-independent manner in nonobese diabetic mice. J. Immunol. Res., 2018, 20185463879
[8]
Dudek, A.; Martin, S.; Garg, A.; Agostinis, P. Immature, semi-mature, and fully mature dendritic cells: toward a DC-cancer cells interface that augments anticancer immunity. Front. Immunol., 2013, 4, 1-14.
[9]
Anguille, S.; Smits, E.L.; Lion, E.; van Tendeloo, V.F.; Berneman, Z.N. Clinical use of dendritic cells for cancer therapy. Lancet Oncol., 2014, 15, e257-e267.
[10]
Kantoff, P.; Higano, C.; Shore, N.; Berger, R.; Small, E.; Penson, D.; Redfern, C.; Ferrari, A.; Dreicer, R.; Sims, R.; Xu, Y.; Frohlich, M.; Schellhammer, P.F. IMPACT Study Investigators Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med., 2010, 363, 411-422.
[11]
Anassi, E.; Anadu, U. Sipuleucel-T (Provenge) injection the firstimmunotherapy agent (vaccine) for hormone-refractory prostate cancer. PT, 2011, 36, 197-202.
[12]
Graff, J.; Chamberlain, E. Sipuleucel-T in the treatment of prostate cancer: an evidence-based review of its place in therapy. Core Evid., 2015, 10, 1-10.
[13]
Madan, R.; Gulley, J. Sipuleucel-T: Harbinger of a new age of therapeutics for prostate cancer. Expert Rev. Vaccines, 2011, 10, 141-150.
[14]
Cui, D.; Gao, H. Advance and prospect of bionanomaterials. Biotechnol. Prog., 2003, 19, 683-692.
[15]
Shi, J.; Votruba, A.; Farokhzad, O.; Langer, R. Nanotechnology in drug delivery and tissue engineering: From discovery to applications. Nano Lett., 2010, 10(9), 3223-3230.
[16]
Wicki, A.; Witzigmann, D.; Balasubramanian, V.; Huwyler, J. Nanomedicine in cancer therapy: Challenges, opportunities, and clinical applications. J. Control. Release, 2015, 200, 138-157.
[17]
Shahverdi, A.R.; Fakhimi, A.; Shahverdi, H.R.; Minaian, S. Synthesis and effect of silver nanoparticles on the antibacterial activity of different antibiotics against Staphylococcus aureus and Escherichia coli. Nanomedicine , 2007, 3, 168-171.
[18]
Jain, S.; Hirst, D.G.; O’Sullivan, J.M. Gold nanoparticles as novel agents for cancer therapy. Br. J. Radiol., 2012, 85, 101-113.
[19]
Hu, Y.; Qi, W.; Han, F.; Shao, J.; Gao, J. Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model. Int. J. Nanomedicine, 2011, 6, 3351-3359.
[20]
Cheung, R.; Ng, T.; Wong, J.; Chan, W. Chitosan: An update on potential biomedical and pharmaceutical applications. Mar. Drugs, 2015, 13, 5156-5186.
[21]
Croisier, F.; Jérôme, C. Chitosan-based biomaterials for tissue engineering. Eur. Polym. J., 2013, 49, 780-792.
[22]
Ahmed, S.; Ikram, S. Chitosan based scaffolds and their applications in wound healing. Achiev. Life Sci, 2016, 10, 27-37.
[23]
Chaochai, T.; Miyaji, H.; Yoshida, T.; Nishida, E.; Furuike, T.; Tamura, H. Preparation of chitosan-gelatin based sponge cross-linked with GLcNAc for bone tissue engineering. J. Chitin Chitosan Sci, 2016, 4, 1-8.
[24]
Pandey, A.; Singh, U.; Momin, M.; Bhavsar, C. Chitosan: Application in tissue engineering and skin grafting. J. Polym. Res., 2017, 24, 1-22.
[25]
Stricker-Krongrad, A.; Alikhassy, Z.; Matsangos, N.; Sebastian, R.; Marti, G.; Lay, F.; Harmon, J. Efficacy of chitosan-based dressing for control of bleeding in excisional wounds. Eplasty, 2018, 18e14
[26]
Tajmir-Riahi, H.; Nafisi, S.; Sanyakamdhorn, S.; Agudelo, D.; Chanphai, P. Applications of chitosan nanoparticles in drug delivery. Methods Mol. Biol., 2014, 1141, 165-184.
[27]
Mansur, H.; Mansur, A.; Soriano-Araújo, A.; Lobato, P. Beyond biocompatibility: An approach for the synthesis of ZnS quantum dot-chitosan nano-immunoconjugates for cancer diagnosis. Green Chem., 2015, 17, 1820-1830.
[28]
Jayakumar, R.; Menon, D.; Manzoor, K.; Nair, S.V.; Tamura, H. Biomedical applications of chitin and chitosan based nanomaterials - A short review. Carbohydr. Polym., 2010, 82, 227-232.
[29]
Patel, L.N.; Zaro, J.L.; Shen, W-C. Cell penetrating peptides: Intracellular pathways and pharmaceutical perspectives. Pharm. Res., 2007, 24, 1977-1992.
[30]
Zhang, S.; Li, J.; Lykotrafitis, G.; Bao, G.; Suresh, S. Size-dependent endocytosis of nanoparticles. Adv. Mater., 2009, 21, 419-424.
[31]
Oh, N.; Park, J. Endocytosis and exocytosis of nanoparticles in mammalian cells. Int. J. Nanomedicine, 2014, 9, 51-63.
[32]
Bannunah, A.; Vllasaliu, D.; Lord, J.; Stolnik, S. Mechanisms of nanoparticle internalization and transport across an intestinal epithelial cell model: effect of size and surface charge. Mol. Pharm., 2014, 11, 4363-4373.
[33]
Nam, H.Y.; Kwon, S.M.; Chung, H.; Lee, S.Y.; Kwon, S.H.; Jeon, H.; Kim, Y.; Park, J.H.; Kim, J.; Her, S.; Oh, Y.K.; Kwon, I.C.; Kim, K.; Jeong, S.Y. Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles. J. Control. Release, 2009, 135, 259-267.
[34]
Agarwala, R.; Singhb, V.; Jurneyb, P.; Shib, L.; Sreenivasanb, S.; Roy, K. Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms. PNAS., 2013, 110, 17247-17252.
[35]
(a)Kankaanpää, P.; Tiitta, S.; Bergman, L.; Puranen, A.; von Haartman, E.; Lindén, M.; Heino, J. Cellular recognition and macropinocytosis-like internalization of nanoparticles targeted to integrin α2β1. Nanoscale, 2015, 7, 17889-17901.
(b)Longfa, K.; Sun, J.; Zhai, Y.; He, Z. The endocytosis and intracellular fate of nanomedicines: Implication for rational design. Asian J. Pharm. Sci, 2013, 8, 1-10.
[36]
Jin, H.; Heller, D.A.; Sharma, R.; Strano, M.S. Size-dependent cellular uptake and expulsion of single-walled carbon nanotubes: Single particle tracking and a generic uptake model for nanoparticles. ACS Nano, 2009, 3, 149-158.
[37]
Mohammed, M.; Syeda, J.; Wasan, K.; Wasan, E. An overview of chitosan nanoparticles and its application in non-parenteral drug delivery. Pharmaceutics, 2017, 9, 1-26.
[38]
Elgadira, A.; Uddinb, S.; Ferdoshc, S.; Adam, A.; Khan, A.; Zaidul, I. Impact of chitosan composites and chitosan nanoparticle composites on various drug delivery systems: A review. J. Food Drug Anal.,, 2015, 23, 619-629.
[39]
Young, S.; Hwa, S.; Park, J.; Jeong, S.; Ho, J.; Su, K.; Lee, K.; Yang, S.; Joo, S.; Dong, P.; Lee, S. Cellular uptake and cytotoxicity of positively charged chitosan gold nanoparticles in human lung adenocarcinoma cells. J. Nanopart. Res., 2012, 14, 1-13.
[40]
Vimal, S.; Abdul Majeed, S.; Taju, G.; Nambi, K.S.; Sundar Raj, N.; Madan, N.; Farook, M.A.; Rajkumar, T.; Gopinath, D.; Sahul Hameed, A.S. Chitosan tripolyphosphate (CS/TPP) nanoparticles: preparation, characterization and application for gene delivery in shrimp. Acta Trop., 2013, 128, 486-493.
[41]
Martins, A.; Oliveira, D.; Pereira, A.; Rubira, A.; Muniz, E. Chitosan/TPP microparticles obtained by microemulsion method applied in controlled release of heparin. Int. J. Biol. Macromol., 2012, 51, 1127-1133.
[42]
Mudunkotuwa, A.; Minshid, A.; Grassian, V. ATR-FTIR spectroscopy as a tool to probe surface adsorption on nanoparticles at the liquid-solid interface in environmentally and biologically relevant media. Analyst , 2014, 139, 870-881.
[43]
Yongmei, X.; Yumin, D. Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles. Int. J. Pharm., 2003, 250, 215-226.
[44]
Boonsongrit, Y.; Mueller, B.; Mitrevej, A. Characterization of drug-chitosan interaction by 1H NMR, FTIR and isothermal titration calorimetry. Eur. J. Pharm. Biopharm., 2008, 69, 388-395.
[45]
Castiello, L.; Sabatino, M.; Zhao, Y.; Tumaini, B.; Ren, J.; Ping, J.; Wang, E.; Wood, L.; Marincola, F.; Puri, R.; Stroncek, D. Quality controls in cellular immunotherapies: Rapid assessment of clinical grade dendritic cells by gene expression profiling. Mol. Ther., 2013, 21, 476-484.
[46]
Curbishley, S.; Blahova, M.; Adams, D. Designing a dendritic cell– based therapy for primary liver cancer. MACS&more, 2016, 17, 20-23.
[47]
Sabado, R.L.; Miller, E.; Spadaccia, M.; Vengco, I.; Hasan, F.; Bhardwaj, N. Preparation of tumor antigen-loaded mature dendritic cells for immunotherapy. J. Vis. Exp., 2013, (78), 50085.
[48]
Fujimasa, T.; Masanori, A.; Masashi, H.; Yoshiou, I.; Yoichi, H.; Yoon, L.; Nam-Chul, J.; Woo-Bok, L.; Hyun-Soo, L.; Yong-Soo, B.; Morikazu, O. Phase I/II study of immunotherapy using tumor antigen-pulsed dendritic cells in patients with hepatocellular carcinoma. Int. J. Oncol., 2012, 41, 1601-1609.
[49]
Xi, H.B.; Wang, G.X.; Fu, B.; Liu, W.P.; Li, Y. Survivin and PSMA loaded dendritic cell vaccine for the treatment of prostate cancer. Biol. Pharm. Bull., 2015, 28, 827-835.
[50]
Nchinda, G.; Amadu, D.; Trumpfheller, C.; Mizenina, O.; Überla, K.; Steinman, R. Dendritic cell targeted HIV gag protein vaccine provides help to a DNA vaccine including mobilization of protective CD8+ T cells. Proc. Natl. Acad. Sci. USA, 2010, 107, 4281-4286.
[51]
Kawamura, K.; Iyonaga, K.; Ichiyasu, H.; Nagano, J.; Suga, M.; Sasaki, Y. Differentiation, maturation, and survival of dendritic cells by osteopontin regulation. Clin. Diagn. Lab. Immunol., 2005, 12, 206-212.
[52]
Montagna, D.; Sommi, P.; Necchi, V.; Vitali, A.; Montini, E.; Turin, I.; Ferraro, D.; Ricci, V.; Solcia, E. Different polyubiquitinated bodies in human dendritic cells: IL-4 causes PaCS during differentiation while LPS or IFNα induces DALIS during maturation. Sci. Rep., 2017, 7, 1844.
[53]
Abediankenari, S.; Yousefzadeh, Y.; Azadeh, H.; Vahedi, M. Comparison of several maturation inducing factors in dendritic cell differentiation. Iran. J. Immunol., 2010, 7, 83-87.
[54]
Mitra, A.; Joshi, S.; Arjun, C.; Kulkarni, S.; Rajan, R. Limulus amebocyte lysate testing: Adapting it for determination of bacterial endotoxin in 99mtc-labeled radiopharmaceuticals at a hospital radiopharmacy. J. Nucl. Med. Technol., 2014, 42, 278-282.
[55]
Schnurr, M.; Galambos, P.; Scholz, C.; Then, F.; Dauer, M.; Endres, S.; Eigler, A. Tumor cell lysate-pulsed human dendritic cells induce a T-cell response against pancreatic carcinoma cells: An in vitro model for the assessment of tumor vaccines. Cancer Res., 2001, 61, 6445-6450.
[56]
Butterfield, L.H. Dendritic cells in cancer immunotherapy clinical trials: Are we making progress? Front. Immunol., 2013, 4, 454.
[57]
(a)Pyzer, A.; Avigan, D.; Rosenblatt, J. Clinical trials of dendritic cell-based cancer vaccines in hematologic malignancies. Hum. Vaccin. Immunother., 2014, 10, 3125-3131.
(b)Bol, K.; Schreibelt, G.; Gerritsen, W.; de Vries, I.; Figdor, C. Dendritic cell–based immunotherapy: state of the art and beyond. Clin. Cancer Res., 2016, 22, 1897-1906.
[58]
Chao, T.; Xiaowen, W.; Zhiqi, L. Qi1, Y.; Zixiao, Y.; Kun, F.; Hoon, D.; Wei1, H. A systemic review of clinical trials on dendritic-cells based vaccine against malignant glioma. J. Carcinog. Mutagen., 2015, 6, 222.
[59]
Antonarakis, E.; Small, E.; Petrylak, D.; Quinn, D.; Kibel, A.; Chang, N.; Dearstyne, E.; Harmon, M.; Campogan, D.; Haynes, H.; Vu, T.; Sheikh, N.; Drake, C. Antigen-specific CD8 lytic phenotype induced by Sipuleucel-T in hormone-sensitive or castration-resistant prostate cancer and association with overall survival. Clin. Cancer Res., 2018, 24(19), 4662-4671.
[60]
Babensee, J.E.; Paranjpe, A. Differential levels of dendritic cell maturation on different biomaterials used in combination products. J. Biomed. Mater. Res., 2005, 74A, 503-510.
[61]
Jia, L.; Gao, X.; Wang, Y.; Yao, N.; Zhang, X. Structural, phenotypic and functional maturation of bone marrow dendritic cells (BMDCs) induced by Chitosan (CTS). Biologicals, 2014, 42, 334-338.
[62]
Lin, Y-C.; Lou, P-J.; Young, T-H. Chitosan as an adjuvant-like substrate for dendritic cell culture to enhance antitumor effects. Biomaterials, 2014, 35, 8867-8875.
[63]
Zargar, V.; Asghari, M.; Dashti, A. A review on chitin and chitosan polymers: Structure, chemistry, solubility, derivatives, and applications. ChemBioEng Rev, 2015, 2, 204-226.
[64]
Bellich, B.; D’Agostino, I.; Semeraro, S.; Gamini, A.; Cesàro, A. The good, the bad and the ugly” of chitosans. Mar. Drugs, 2016, 14E99
[65]
Tseng, S-Y.; Dustin, M.L. T-cell activation: A multidimensional signaling network. Curr. Opin. Cell Biol., 2002, 14, 575-580.
[66]
van Rijt, L.; Vos, N.; Willart, M.; Kleinjan, A.; Coyle, A.; Hoogsteden, H.; Lambrecht, B. Essential role of dendritic cell CD80/CD86 costimulation in the induction, but not reactivation, of TH2 effector responses in a mouse model of asthma. J. Allergy Clin. Immunol., 2004, 114, 166-173.
[67]
Schefold, J.; Porz, L.; Uebe, B.; Poehlmann, H.; von Haehling, S.; Jung, A.; Unterwalder, N.; Meisel, C. Diminished HLA-DR expression on monocyte and dendritic cell subsets indicating impairment of cellular immunity in pre-term neonates: A prospective observational analysis. J. Perinat. Med., 2015, 43, 609-618.
[68]
Ten Broeke, T.; Wubbolts, R.; Stoorvogel, W. MHC class II antigen presentation by dendritic cells regulated through endosomal sorting. Cold Spring Harb. Perspect. Biol., 2013, 5(12)a016873
[69]
Aerts-Toegaert, C.; Heirman, C.; Tuyaerts, S.; Corthals, J.; Aerts, J.; Bonehill, A.; Thielemans, K.; Breckpot, K. CD83 expression on dendritic cells and T cells: correlation with effective immune responses. Eur. J. Immunol., 2007, 37(3), 686-695.
[70]
Villiers, C.; Chevallet, M.; Diemer, H.; Couderc, R.; Freitas, H.; Van Dorsselaer, A.; Marche, P.N.; Rabilloud, T. From secretome analysis to immunology: Chitosan induces major alterations in the activation of dendritic cells via a TLR4-dependent mechanism. Mol. Cell. Proteomics, 2009, 8, 1252-1264.
[71]
Arroyo-Espliguero, R.; Avanzas, P.; Jeffery, S.; Kaski, J.C. CD14 and toll-like receptor 4: A link between infection and acute coronary events? Heart, 2004, 90, 983-988.
[72]
Guilliams, M.; Ginhoux, F.; Jakubzick, C.; Naik, S.H.; Onai, N.; Schraml, B.U.; Segura, E.; Tussiwand, R.; Yona, S. Dendritic cells, monocytes and macrophages: A unified nomenclature based on ontogeny. Nat. Rev. Immunol., 2014, 14, 571-578.
[73]
Pham, P.V.; Nguyen, N.T.; Nguyen, H.M.; Khuat, L.T.; Le, P.M.; Pham, V.Q.; Nguyen, S.T.; Phan, N.K. A simple in vitro method for evaluating dendritic cell-based vaccinations. OncoTargets Ther., 2014, 7, 1455-1464.
[74]
Teitz-Tennenbaum, S.; Li, Q.; Davis, M.A.; Chang, A.E. Dendritic cells pulsed with keyhole limpet hemocyanin and cryopreserved maintain anti-tumor activity in a murine melanoma model. Clin. Immunol., 2008, 129, 482-491.
[75]
Presicce, P.; Taddeo, A.; Conti, A.; Villa, M.L.; Bella, S.D. Keyhole limpet hemocyanin induces the activation and maturation of human dendritic cells through the involvement of mannose receptor. Mol. Immunol., 2008, 45, 1136-1145.

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