Self-assembled nanoparticles based on folic acid modified carboxymethyl chitosan conjugated with targeting antibody

Abstract

Nanoparticles conjugated with antibody were designed as active drug delivery system to reduce the toxicity and side effects of drugs for acute myeloid leukemia (AML). Moreover, methotrexate (MTX) was chosen as model drug and encapsulate within folic acid modified carboxymethyl chitosan (FA-CMCS) nanoparticles through self-assembling. The chemical structure, morphology, release and targeting of nanoparticles were characterized by routine detection. It is demonstrated that the mean diameter is about 150 nm, the release rate increases with the decreasing of pH, the binding rate of CD33 antibody and FA-CMCS nanoparticles is about 5:2, and nanoparticles can effectively bind onto HL60 cells in vitro. The experimental results indicate that the FA-CMCS nanoparticles conjugated with antibody may be used as a potential pHsensitive drug delivery system with leukemic targeting properties.

Keywords

chitosan / nanoparticles / targeted drug delivery / cancer / controlled release / self-assembly / pH-sensitive

References

[1] Pae HO, Seo WG, Kim NY, et al. Induction of Granulocytic Differentiation in Acute Promyelocytic Leukemia Cells (HL-60) by Watersoluble Chitosan Oligomer[J]. Leukemia Res., 2001, 25(4): 339-346.

[2] Sievers EL. Targeted Therapy of Acute Myeloid Leukemia with Monoclonal Antibody and Immunoconjugates[J]. Cancer Chemother Pharmacol., 2000, 46: S18-S22.

[3] Choi KY, Chung H, Min KH, et al. Self-assembled Hyaluronic Acid Nanoparticles for Active Tumor Targeting[J]. Biomaterials, 2010, 31(1): 106-114.

[4] Chen NY, Hung AFH, Lin CJ, et al. Manipulating mIgD-expressing B Cells with Anti-migis-d Monoclonal Antibodies[J]. Mol Immunol., 2013, 53(3): 187-197.

[5] Sood N, Chaudhary DK, Singh A, et al. Monoclonal Antibody to Serum Immunoglobulins of Clarias Batrachus and Its Application in Immunoassays[J]. Gene, 2012, 511(2): 411-419.

[6] Andrews RG, Singer JW, Bernstein ID. Precursors of Colony-forming Cells in Humans can be Distinguished from Colony-forming Cells by Expression of the CD33 and CD34 Antigens and Light Scatter Properties[J]. J. Exp. Med., 1989, 169(5): 1721-1731.

[7] Siao SC, Li KJ, Hsieh SC, et al. Tamm-Horsfall Glycoprotein Enhances PMN Phagocytosis by Binding to Cell Surface-Expressed Lactoferrin and Cathepsin G That Activates MAP Kinase Pathway [J]. Molecules, 2011, 16(3): 2119-2134.

[8] Ji J, Wu D, Liu L, et al. Preparation, Evaluation, and In Vitro Release of Folic Acid Conjugated O-Carboxymethyl Chitosan Nanoparticles Loaded with Methotrexate[J]. J. Appl. Polym. Sci., 2012, 125(S2): E208-E215.

[9] Pfeffer M, Maurer M, Stadlmann J, et al. Intracellular Interactome of Secreted Antibody Fab Fragment in Pichia Pastorisreveals its Routes of Secretion and Degradation[J]. Appl. Microbiol. Biot., 2012, 93(6): 2503-2512.

[10] Tan Y, Liu CG. Preparation and Characterization of Self-assemblied Nanoparticles Based on Folic Acid Modified Carboxymethyl Chitosan[J]. J. Mater. Sci-Mater. M., 2011, 22(5): 1213-1220.

[11] Saboktakin MR, Tabatabaie RM, Maharramov A, et al. Synthesis and in Vitro Evaluation of Carboxymethyl Starch–Chitosan Nanoparticles as Drug Delivery System to the Colon[J]. Int J Biol Macromol., 2011, 48(3): 381-385.

[12] Yang SJ, Lin FH, Tsai KC, et al. Folic Acid-Conjugated Chitosan Nanoparticles Enhanced Protoporphyrin IX Accumulation in Colorectal Cancer Cells[J]. Bioconjugate Chem., 2010, 21(4): 679-689.

[13] Wang F, Zhang D, Duan C, et al. Preparation and Characterizations of a Novel Deoxycholic Acid-O-Carboxymethylated Chitosan-Folic Acid Conjugates and Self-aggregates[J]. Carbohyd. Polym., 2011, 84(3): 1192-1200.

[14] Mathew MZ, Mohan JC, Manzoor K, et al. Folate Conjugated Carboxymethyl Chitosan–Manganese Doped Zinc Sulphide Nanoparticles for Targeted Drug Delivery and Imaging of Cancer Cells[J]. Carbohyd Polym., 2010, 80(2): 442-448.

[15] Sahu SK, Mallick SK, Santra S, et al. In Vitro Evaluation of Folic Acid Modified Carboxymethyl Chitosan Nanoparticles Loaded with Doxorubicin for Targeted Delivery[J]. J. Mater. Sci. -Mater. M., 2010, 21(5): 1587-1597.

[16] Nor NM, Razak KA, Tan SC, et al. Properties of Surface Functionalized Iron Oxide Nanoparticles (Ferrofluid) Conjugated Antibody for Lateral Flow Immunoassay Application[J]. J. Alloy. Compd., 2012, 538: 100-106.

[17] Mercaderc JV, Esteve-Turrillas FA, Agulló C, et al. Antibody Generation and Immunoassay Development in Diverse Formats for Pyrimethanil Specific and Sensitive Analysis[J]. Analyst., 2012, 137: 5672-5679.

[18] Ulbrich K, Šubr V, Strohalm J, et al. Polymeric Drugs Based on Conjugates of Synthetic and Natural Macromolecules I. Synthesis and Physico-chemical Characterization[J]. J. Control Release., 2000, 64(1-3): 63-79.

[19] Liu P, Qin L, Wang Q, et al. cRGD-functionalized mPEG-PLGAPLL Nanoparticles for Imaging and Therapy of Breast Cancer[J]. Biomaterials, 2012, 33(28): 6739-6747.

[20] Zhou Y, Tian XL, Li YS, et al. Development of a Monoclonal Antibodybased Sandwich-type Enzyme-linked Immunosorbent Assay (ELISA) for Detection of Abrin in Food Samples[J]. Food Chem., 2012, 135(4): 2661-2665.

[21] Houot R, Kohrt H, Goldstein MJ, et al. Immunomodulating Antibodies and Drugs for the Treatment of Hematological Malignancies[J]. Cancer Metast Rev., 2011, 30(1): 97-109.

[22] Simard P, Leroux JC. In Vivo Evaluation of pH-Sensitive Polymer-Based Immunoliposomes Targeting the CD33 Antigen[J]. Mol. Pharm., 2010, 7(4): 1098-1107.