Anti-EGFR-mAb and 5-Fluorouracil Conjugated Polymeric Nanoparticles for Colorectal Cancer | Bentham Science
Login Register Cart 0
Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

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

Anti-EGFR-mAb and 5-Fluorouracil Conjugated Polymeric Nanoparticles for Colorectal Cancer

Author(s): Sankha Bhattacharya*

Volume 16, Issue 1, 2021

Published on: 21 December, 2020

Page: [84 - 100] Pages: 17

DOI: 10.2174/1574892815666201221121859

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Due to the higher intake of junk food and unhealthy lifestyle, the percentage of U.S. adults aged 50 to 75 years who were up-to-date with colorectal cancer screening increased 1.4 percentage points, from 67.4% in 2016 to 68.8% in 2018. This represents an additional 3.5 million adults screened for colorectal cancer. This is a severe concern of this research, and an attempt was made to prepare a target-specific formulation that could circumvent chemotherapy-related compilation and improvise higher cellular uptake. The fundamental agenda of this research was to prepare and develop Anti-EGFR mAb and 5-Fluorouracil (5-FU) fabricated polymeric nanoparticles for colorectal cancer.

Objective: The main objective of this research was to prepare and evaluate more target specific formulation for the treatment of colorectal cancer. PLGA and PEG-based polymeric nanoparticles are capable of preventing opsonization via the reticuloendothelial system. Hence, prepared polymeric nanoparticles are capable of higher cellular uptake.

Methods: The Poly(d,1-lactide-co-glycolide) (PLGA) and Polyethylene Glycol (PEG) were combined utilizing the ring-opening polymerization method. The presence of PEG prevents opsonization and distinguished blood concentration along with enhanced targeting. The presence of PLGA benefits in the sustained release of polymeric formulations. The optimized formulation (5-FU-PLGA- PEG-NP) was lyophilized using 4% trehalose (cryoprotectants) and conjugated with Anti- EGFR mAb on its surface to produce Anti-EGFR-5-FU-PLGA-PEG-NP; the final formulation, which increases target specificity and drug delivery system of nanoparticles.

Results: The spherical shaped optimized formulation, 5-FU-PLGA-PEG-NP-3 was found to have higher percentage drug entrapment efficacy (71.23%), higher percentage drug content (1.98 ± 0.34%) with minimum particles size (252.3nm) and anionic zeta potential (-31.23mV). The IC50 value of Anti-EGFR-5-FU-PLGA-PEG-NP was 1.01μg/mL after 48 hours incubation period in the HCT 116 cell line, indicating higher anticancer effects of the final formulation.

Conclusion: From the outcomes of various experiments, it was concluded that Anti-EGFR-5-FUPLGA- PEG-NP has biphasic drug release kinetics, higher cellular uptake and higher cytotoxicity. Therefore, anti-EGFR-5-FU-PLGA-PEG-NP holds excellent potential for drug delivery to EGFR positive colorectal cancer cells.

Keywords: 5-Fluorouracil, anti-EGFR, HCT116 cells, IC50 value, PLGA-PEG nanoparticles, sulforhodamine B assay.

« Previous Next »
[1]
Heydebreck CSV. Biomarkers and methods for determining efficacy of anti-EGFR antibodies in cancer therapy. Merck Patent GmbH: French. 2012.
[2]
De Rosa M, Pace U, Rega D, et al. Genetics, diagnosis and management of colorectal cancer. Oncol Rep 2015; 34(3): 1087-96.
[http://dx.doi.org/10.3892/or.2015.4108]
[3]
Herszenyi L, Tulassay ZJERMPS. Epidemiology of gastrointestinal and liver tumors. Eur Rev Med Pharmacol Sci 2010; 14(4): 249-58.
[4]
Ong BA, Vega KJ, Houchen CW. Intestinal stem cells and the colorectal cancer microenvironment. World J Gastroenterol 2014; 20(8): 1898-909.
[http://dx.doi.org/10.3748/wjg.v20.i8.1898]
[5]
Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancer-initiating cells. Nature 2007; 445(7123): 111-5.
[http://dx.doi.org/10.1038/nature05384]
[6]
Hamzehzadeh L, Yousefi M, Ghaffari S-H. Colorectal cancer screening: A comprehensive review to recent non-invasive methods. Int J Hematol Oncol Stem Cell Res 2017; 11(3): 250-61.
[7]
DeLuca JA, Garcia-Villatoro EL, Allred CD. Flaxseed bioactive compounds and colorectal cancer prevention. Curr Oncol Rep 2018; 20(8): 59.
[http://dx.doi.org/10.1007/s11912-018-0704-z]
[8]
Freeman HJ. Early stage colon cancer. World J Gastroenterol 2013; 19(46): 8468-73.
[http://dx.doi.org/10.3748/wjg.v19.i46.8468]
[9]
Testa U, Pelosi E, Castelli GJMS. Colorectal cancer: Genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells. Med Sci (Basel) 2018; 6(2): 31.
[10]
Haggar FA, Boushey RP. Colorectal cancer epidemiology: Incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg 2009; 22(4): 191-7.
[http://dx.doi.org/10.1055/s-0029-1242458]
[11]
Fijten GH, Starmans R, Muris JWM, Schouten HJA, Blijham GH, Knottnerus JA. Predictive value of signs and symptoms for colorectal cancer in patients with rectal bleeding in general practice. Fam Pract 1995; 12(3): 279-86.
[http://dx.doi.org/10.1093/fampra/12.3.279]
[12]
Andre N, Schmiegel W. Chemoradiotherapy for colorectal cancer. Gut 2005; 54(8): 1194-202.
[http://dx.doi.org/10.1136/gut.2004.062745]
[13]
Liu L-X, Zhang W-H, Jiang H-C. Current treatment for liver metastases from colorectal cancer. World J Gastroenterol 2003; 9(2): 193.
[http://dx.doi.org/10.3748/wjg.v9.i2.193]
[14]
Shull AY, Latham-Schwark A, Ramasamy P, et al. Novel somatic mutations to PI3K pathway genes in metastatic melanoma. PloS One 2012; 7(8): e43369.
[15]
Saddiq M, Kankara A, Dutsin-Ma UA. Prevalence of Rifampicin Mono Resistant Mycobacterium tuberculosis among patients Attending Federal Medical Centre, Katsina, Nigeria. SJMLS 2017; 2(1): 90-4.
[16]
Pardini B, Kumar R, Naccarati A, et al. 5-Fluorouracil-based chemotherapy for colorectal cancer and MTHFR/MTRR genotypes. Br J Clin Pharmacol 2011; 72(1): 162-3.
[http://dx.doi.org/10.1111/j.1365-2125.2010.03892.x]
[17]
Cirillo G, Puoci FF, Parisi OI, Curcio M, Spizzirri UG, Picci N. Imprinted hydrophilic nanospheres as drug delivery systems for 5-fluorouracil sustained release. Drug Target 2009; 17(1): 72-7.
[18]
Adjei AA. A review of the pharmacology and clinical activity of new chemotherapy agents for the treatment of colorectal cancer. BJCP 1999; 48(3): 265-77.
[http://dx.doi.org/10.1046/j.1365-2125.1999.00010.x]
[19]
Ichikawa W, Ooyama A, Toda E, et al. Gene expression of ferredoxin reductase predicts outcome in patients with metastatic colorectal cancer treated by 5-fluorouracil plus leucovorin. Cancer Chemother Pharmacol 2006; 58(6): 794-801.
[20]
Danenberg PV, Malli H, Swenson S. Thymidylate synthase inhibitors. Semin Oncol 1999; 26(6): 621-31.
[21]
Garabalino MA, Hughes AM, Molinari AJ, et al. Boron Neutron Capture Therapy (BNCT) for the treatment of liver metastases: Biodistribution studies of boron compounds in an experimental model. Radiat Environ Biophys 2011; 50(1): 199-207.
[22]
Poste G, Kirsh R. Site-specific (targeted) drug delivery in cancer therapy. Nat Biotechnol 1983; 1(10): 869-78.
[23]
Miller MA, Arlauckas S, Weissleder RJN. Prediction of anti- cancer nanotherapy efficacy by imaging. Nanotheranostics 2017; 1(3): 296-312.
[http://dx.doi.org/10.7150/ntno.20564]
[24]
Tummala S, Satish Kumar MN, Prakash A. Formulation and characterization of 5-Fluorouracil enteric coated nanoparticles for sustained and localized release in treating colorectal cancer. Saudi Pharm J 2015; 23(3): 308-14.
[25]
Tığlı Aydın RS, Pulat M. 5-Fluorouracil encapsulated chitosan nanoparticles for pH-stimulated drug delivery: Evaluation of controlled release kinetics. J Nanomater 2012; 2012: 313961.
[26]
Kotla NG, Rana S, Sivaraman G, et al. Bioresponsive drug delivery systems in intestinal inflammation: State-of-the-art and future perspectives. Adv Drug Deliv Rev 2019; 146: 248-66.
[http://dx.doi.org/10.1016/j.addr.2018.06.021]
[27]
Debele TA, Mekuria SL, Tsai H-C, et al. Polysaccharide based nanogels in the drug delivery system: Application as the carrier of pharmaceutical agents. Mater Sci Eng C 2016; 68: 964-81.
[http://dx.doi.org/10.1016/j.msec.2016.05.121]
[28]
Probst CE, Zrazhevskiy P, Bagalkot V, Gao X. Quantum dots as a platform for nanoparticle drug delivery vehicle design. Adv Drug Deliv Rev 2013; 35(5): 703-18.
[http://dx.doi.org/10.1016/j.addr.2012.09.036]
[29]
Kumar Khanna V. Targeted delivery of nanomedicines. ISRN Pharmacol 2012; 2012: 571394-4.
[http://dx.doi.org/10.5402/2012/571394]
[30]
Kingsley JD, Dou H, Morehead J, Rabinow B, Gendelman HE, Destache CJ. Nanotechnology: A focus on nanoparticles as a drug delivery system. 2006; 1(3): 340-50.
[31]
Makadia HK, Siegel SJ. Poly Lactic-co-Glycolic Acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers (Basel) 2011; 3(3): 1377-97.
[http://dx.doi.org/10.3390/polym3031377]
[32]
Sinha VR, Trehan A. Biodegradable microspheres for parenteral delivery. Crit Rev Ther Drug Carrier Syst 2005; 22(6): 535-602.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.v22.i6.20]
[33]
Dechy-Cabaret O, Martin-Vaca B, Bourissou D. Controlled ring-opening polymerization of lactide and glycolide. Chem Rev 2004; 104(12): 6147-76.
[http://dx.doi.org/10.1021/cr040002s]
[34]
Pounder RJ, Dove APJPC. Towards poly (ester) nanoparticles: Recent advances in the synthesis of functional poly (ester) s by ring-opening polymerization. Polym Chem 2010; 1(3): 260-71.
[35]
Zidan OH. PEGylated chitosan/doxorubicin nanoparticles and conjugated with monoclonal antibodies for breast cancer therapy MS Dissertation American University in Cairo, Egypt. June, 2020.
[36]
Bhargava P, Zheng JX, Li P, Quirk RP, Harris FW, Cheng SZD. Self-assembled polystyrene-block-poly(ethylene oxide) micelle morphologies in solution. Macromolecules 2006; 39(14): 4880-8.
[http://dx.doi.org/10.1021/ma060677s]
[37]
Zhao L, Shen G, Ma G, Yan X. Engineering and delivery of nanocolloids of hydrophobic drugs. Adv Colloid Interface Sci 2017; 249: 308-20.
[http://dx.doi.org/10.1016/j.cis.2017.04.008]
[38]
Hamley IW. PEG-peptide conjugates. Biomacromolecules 2014; 15(5): 1543-59.
[http://dx.doi.org/10.1021/bm500246w]
[39]
Uskoković V, Uskoković DP. Nanotechnologies in preventive and regenerative medicine: Quo Vadis, Domine? Nanotechnologies in preventive and regenerative medicine Elsevier. 2018; pp. pp. 513-566.
[40]
Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev 2014; 66: 2-25.
[http://dx.doi.org/10.1016/j.addr.2013.11.009]
[41]
Brekke OH, Sandlie I. Therapeutic antibodies for human diseases at the dawn of the twenty-first century. Nat Rev Drug Discov 2003; 2(1): 52-62.
[42]
Liu R-X, Ren W-Y, Ma Y, et al. BMP7 mediates the anticancer effect of honokiol by upregulating p53 in HCT116 cells. Int J Oncol 2017; 51(3): 907-17.
[http://dx.doi.org/10.3892/ijo.2017.4078]
[43]
Wee P, Wang Z. Epidermal growth factor receptor cell proliferation signaling pathways. Cancers (Basel) 2017; 9(5): 52.
[44]
Bertani MF. Analysis of ErbB2-and growth factor dependent gene expression in breast cells. PhD Dissertation United Kingdom University of London, University College London,. 2006.
[45]
Jaiswal BS, Seshagiri S. ERBB3 mutations in cancer. US20130195870, 2013.
[46]
Li R, Xue L, Zhu T, et al. Design and synthesis of 5-aryl-pyridone-carboxamides as inhibitors of anaplastic lymphoma kinase. J Med Chem 2006; 49(3): 1006-15.
[http://dx.doi.org/10.1021/jm050824x]
[47]
Harnish DC, Zhang S, Jin MX. Methods and compositions for selective inhibition of ligand binding to the lectin-like receptor for oxidized low density lipoprotein (LOX-1). US20090311271, 2009.
[48]
Du Z, Lovly CM. Mechanisms of receptor tyrosine kinase activation in cancer. Mol Cancer 2018; 17(1): 58-8.
[http://dx.doi.org/10.1186/s12943-018-0782-4]
[49]
Berezowska S. Targeting heterodimeric EGFR/ErbB2-receptor complexes with novel bispecific small-molecule tyrosine kinase inhibitors in combination with an experimental radiotherapy in human malignant glioma cells. PhD Dissertation, Technische Universität München, Germany, 2009.
[50]
Zhang Z, Qian H, Huang J, et al. Anti-EGFR-iRGD recombinant protein modified biomimetic nanoparticles loaded with gambogic acid to enhance targeting and antitumor ability in colorectal cancer treatment. Int J Nanomedicine 2018; 13: 4961-75.
[http://dx.doi.org/10.2147/IJN.S170148]
[51]
Basu S, Harfouche R, Soni S, Sengupta S. Polymeric nanoparticles with enhanced drug-loading and methods of use thereof. US20120052041, 2012.
[52]
Lee H, Fonge H, Hoang B, Reilly RM, Allen C. The effects of particle size and molecular targeting on the intratumoral and subcellular distribution of polymeric nanoparticles. Mol Pharm 2010; 7(4): 1195-208.
[http://dx.doi.org/10.1021/mp100038h]
[53]
Li B, Li Q, Mo J, Dai H. Drug-loaded polymeric nanoparticles for cancer stem cell targeting. Front Pharmacol 2017; 8: 51-1.
[http://dx.doi.org/10.3389/fphar.2017.00051]
[54]
Danhier F, Ansorena E, Silva JM, Coco R, Breton AL, Preat V. PLGA-based nanoparticles: An overview of biomedical applications. J Control Release 2012; 161(2): 505-22.
[http://dx.doi.org/10.1016/j.jconrel.2012.01.043]
[55]
Elzoghby AO, Samy WM, Elgindy NA. Albumin-based nanoparticles as potential controlled release drug delivery systems. J Control Release 2012; 157(2): 163-82.
[http://dx.doi.org/10.1016/j.jconrel.2011.07.031]
[56]
Liang J-J, Zhou Y-Y, Wu J, Ding Y. Gold nanoparticle-based drug delivery platform for antineoplastic chemotherapy. Curr Drug Metab 2014; 15(6): 620-31.
[http://dx.doi.org/10.2174/1389200215666140605131427]
[57]
Kuo Y-C, Ko H-F. Targeting delivery of saquinavir to the brain using 83-14 monoclonal antibody-grafted solid lipid nanoparticles. Biomaterials 2013; 34(20): 4818-30.
[58]
Yang G-J, Huang J-L, Meng W-J, Shen M, Jiao X-A. A reusable capacitive immunosensor for detection of Salmonella spp. based on grafted ethylene diamine and self-assembled gold nanoparticle monolayers. Anal Chim Acta 2009; 647(2): 159-66.
[59]
Liu Y, Wang W, Yang J, Zhou C, Sun J. pH-sensitive polymeric micelles triggered drug release for extracellular and intracellular drug targeting delivery. Asian J Pharm Sci 2013; 8(3): 159-67.
[60]
Bilodeau MT, Kadiyala S, Shinde R, White B, Wooster R, Barder TE. Targeted conjugates encapsulated in particles and formulations thereof. US20140187501, 2014.
[61]
Cheng J, Tong R. Nanoconjugates and nanoconjugate formulations. US9295651 2016.
[62]
Singh A, Singh S, Gupta AK, Kulkani GM. Pharmaceutical composition comprising at least one anticancer drug and at least one polymer. CN101495148, 2012.
[63]
Radosz M, Xu P, Shen Y. Nanoparticles for cytoplasmic drug delivery to cancer cells. US8945629, 2015.
[64]
Qiao M, Chen D, Ma X, Liu Y. Injectable biodegradable temperature-responsive PLGA-PEG-PLGA copolymers: Synthesis and effect of copolymer composition on the drug release from the copolymer-based hydrogels. Int J Pharm 2005; 294(1-2): 103-12.
[http://dx.doi.org/10.1016/j.ijpharm.2005.01.017]
[65]
Wang Y, Li P, Truong-Dinh Tran T, Zhang J, Kong L. Manufacturing techniques and surface engineering of polymer based nanoparticles for targeted drug delivery to cancer. Nanomaterials (Basel) 2016; 6(2): 26.
[http://dx.doi.org/10.3390/nano6020026]
[66]
Martinelli E, De Palma R, Orditura M, De Vita F, Ciardiello F. Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy. Clin Exp Immunol 2009; 158(1): 1-9.
[http://dx.doi.org/10.1111/j.1365-2249.2009.03992.x]
[67]
Nair KL, Jagadeeshan S, Nair SA, Kumar GS. Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA. Int J Nanomedicine 2011; 6: 1685-97.
[68]
Stahlmann S. Kovar K-AJJoCA. Analysis of impurities by high-performance thin-layer chromatography with Fourier transform infrared spectroscopy and UV absorbance detection in situ measurement: Chlordiazepoxide in bulk powder and in tablets. J Chromatogr A 1998; 813(1): 145-52.
[http://dx.doi.org/10.1016/S0021-9673(98)00334-3]
[69]
Yeung TM, Gandhi SC, Wilding JL, Muschel R, Bodmer WF. Cancer stem cells from colorectal cancer-derived cell lines. Proc Natl Acad Sci USA 2010; 107(8): 3722-7.
[http://dx.doi.org/10.1073/pnas.0915135107]
[70]
Skehan P, Storeng R, Scudiero D, et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 1990; 82(13): 1107-12.
[http://dx.doi.org/10.1093/jnci/82.13.1107]
[71]
Kwan YP, Saito T, Ibrahim D, et al. Evaluation of the cytotoxicity, cell-cycle arrest, and apoptotic induction by Euphorbia hirta in MCF-7 breast cancer cells. Pharm Biol 2016; 54(7): 1223-36.
[72]
Suhail SM, Woo KT, Tan HK, Wong KS. Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE) of urinary protein in acute kidney injury. Saudi J Kidney Dis Transpl 2011; 22(4): 739-45.
[73]
D’Alessandro A, Liumbruno G, Grazzini G, Zolla L. Red blood cell storage: The story so far. Blood Transfus 2010; 8(2): 82-8.
[74]
Bhattacharya S. Fabrication and characterization of chitosan-based polymeric nanoparticles of Imatinib for colorectal cancer targeting application. Int J Biol Macromol 2020; 151: 104-15.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.02.151]
[75]
Kumar A, Kumar R, Sandilium A, Shukla J, Pradhan S. 5-Fluorouracil induces defects in platelet function. Platelets 1999; 10(2-3): 137-40.
[http://dx.doi.org/10.1080/09537109909169176]
[76]
Au JL, Walker JS, Rustum Y. Pharmacokinetic studies of 5-fluorouracil and 5′-deoxy-5-fluorouridine in rats. J Pharmacol Exp Ther 1983; 227(1): 174-80.
[77]
Wang G-H, Wang J, Qi W, Chen Y, Sun L-X. Tissue distribution and excretion of 5-fluorouracil from indomethacin 5-fluorouracil-1-ylmethylester in rats. Yao Xue Xue Bao 2008; 43: 81-5.
[78]
Rezvantalab S, Drude NI, Moraveji MK, et al. PLGA-based nanoparticles in cancer treatment. Front Pharmacol 2018; 9: 1260-0.
[http://dx.doi.org/10.3389/fphar.2018.01260]
[79]
Yamashita-Kashima Y, Iijima S, Yorozu K, et al. Pertuzumab in combination with trastuzumab shows significantly enhanced antitumor activity in HER2-positive human gastric cancer xenograft models. Clin Cancer Res 2011; 17(15): 5060-70.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2927]
[80]
Miyata K, Takemoto A, Okumura S, Nishio M, Fujita N. Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation. Sci Rep 2017; 7(1): 4059.
[http://dx.doi.org/10.1038/s41598-017-04324-1]
[81]
Master AM, Sen Gupta A. EGF receptor-targeted nanocarriers for enhanced cancer treatment. Nanomedicine (Lond) 2012; 7(12): 1895-906.
[http://dx.doi.org/10.2217/nnm.12.160]
[82]
Rafiei P, Haddadi A. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: Pharmacokinetics and biodistribution profile. Int J Nanomedicine 2017; 12: 935-47.
[http://dx.doi.org/10.2147/IJN.S121881]
[83]
Allen DC. Oesophageal carcinoma. Histopathology Reporting Springer. 2013; pp. pp. 3-13.

Rights & Permissions Print Cite
Article Metrics
92
7
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy