Dendrimer-paclitaxel complexes for efficient treatment in ovarian cancer: study on OVCAR-3 and HEK293T cells

• Authors: Hua Yao , Jinqi Ma
• Languages of publication: EN

Abstracts

EN

The present paper investigates the enhancement of the therapeutic effect of Paclitaxel (a potent anticancer drug) by increasing its cellular uptake in the cancerous cells with subsequent reduction in its cytotoxic effects. To fulfill these goals the Paclitaxel (PTX)-Biotinylated PAMAM dendrimer complexes were prepared using biotinylation method. The primary parameter of Biotinylated PAMAM with a terminal HN2 group - the degree of biotinylation - was evaluated using HABA assay. The basic integrity of the complex was studied using DSC. The Drug Loading (DL) and Drug Release (DR) parameters of Biotinylated PAMAM dendrimer-PTX complexes were also examined. Cellular uptake study was performed in OVCAR-3 and HEK293T cells using fluorescence technique. The statistical analysis was also performed to support the experimental data. The results obtained from HABA assay showed the complete biotinylation of PAMAM dendrimer. DSC study confirmed the integrity of the complex as compared with pure drug, biotinylated complex and their physical mixture. Batch 9 showed the highest DL (12.09%) and DR (70%) for 72 h as compared to different concentrations of drug and biotinylated complex. The OVCAR-3 (cancerous) cells were characterized by more intensive cellular uptake of the complexes than HEK293T (normal) cells. The obtained experimental results were supported by the statistical data. The results obtained from both experimental and statistical evaluation confirmed that the biotinylated PAMAM NH2 dendrimer-PTX complex not only displays increased cellular uptake but has also enhanced release up to 72 h with the reduction in cytotoxicity.

Keywords

EN

Paclitaxel; Biotinylated PAMAM NH2 complex; ovarian cancer; cellular uptake; cytotoxicity

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2018
• Volume: 65
• Issue: 2
• Pages: 219-225

Dates

published

2018

received

2017-09-29

revised

2017-10-20

accepted

2017-10-21

(unknown)

2018-06-18

Contributors

author

Hua Yao

• Department of Gynecology and Obstetrics, The second People's Hospital of Nantong, Nantong, Jiangsu 226002, China

author

Jinqi Ma

• Department of Obstetrics, Wuxi People's Hospital, Wuxi, Jiangsu 214023, China

References

• Bankhead CR, Kehoe ST, Austoker J (2005) Symptoms associated with diagnosis of ovarian cancer: a systematic review. BJOG 112: 857-865. 10.1111/j.1471-0528.2005.00572.x.
• Choi JS, Nam K, Park JY, Kim JB, Lee JK, Park JS (2004) Enhanced transfection efficiency of PAMAM dendrimer by surface modification with l-arginine. J Control Release 99: 445-456. 0.1016/j.jconrel.2004.07.027.
• Cragun JM (2011) Screening for ovarian cancer. Cancer Control 18: 16-21.
• Ferris JS, Daly MB, Buys SS, Genkinger JM, Liao Y, Terry MB (2014) Oral contraceptive and reproductive risk factors for ovarian cancer within sisters in the breast cancer family registry. Brit J Cancer 110: 1074-1080. 10.1038/bjc.2013.803.
• Geggel L, Writer S (2014) Ovarian Cancer: Symptoms and Treatment. Live Science 08: 26
• Harley I, Rosen B, Risch HA, et al (2008) Ovarian cancer risk is associated with a common variant in the promoter sequence of the mismatch repair gene MLH1. Gynecol Oncol 109: 384-387. 10.1016/j.ygyno.2007.11.046.
• Kesharwani P, Iyer AK (2015) Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery. Drug Discovery Today 20: 536-547.doi: 10.1016/j.drudis.2014.12.012.
• Kirkpatrick GJ, Plumb JA, Sutcliffe OB, Flint DJ, Wheate NJ (2011) Evaluation of anionic half generation 3.5-6.5 poly(amidoamine) dendrimers as delivery vehicles for the active component of the anticancer drug cisplatin. J Inorg Biochem 105: 1115-1122. 10.1016/j.jinorgbio.2011.05.017.
• Kojima C, Kono K, Maruyama K, Takagishi T (2000) Synthesis of polyamidoamine dendrimers having poly(ethylene glycol) grafts and their ability to encapsulate anticancer drugs. Bioconjug Chem 11: 910-917. 10.1021/bc0000583.
• Lifford KJ, Fraser L, Rosenthal AN, Rogers MT, Lancastle D, Phelps C, Watson EK, Clements A, Iredale R, Jacobs I, Menon U, Brain KE (2012) Withdrawal from familial ovarian cancer screening for surgery: Findings from a psychological evaluation study (PsyFOCS). Gynecol Oncol 124: 158-163. 10.1016/j.ygyno.2011.09.015.
• Ma P, Mumper RJ (2013) Paclitaxel Nano-Delivery Systems: A Comprehensive Review. J Nanomed Nanotechnol 4: 1000164. 10.4172/2157-7439.1000164.
• Majoros IJ, Myc A, Thomas T, Mehta CB, Baker JR Jr. (2006) PAMAM dendrimer-based multifunctional conjugate for cancer therapy: synthesis, characterization, and functionality. Biomacromolecules 7: 572-579. 10.1021/bm0506142.
• Mamede M, Saga T, Kobayashi H, Ishimori T, Higashi T, Sato N, Brechbiel MW, Konishi J (2003) Radiolabeling of avidin with very high specific activity for internal radiation therapy of intraperitoneally disseminated tumors. Clin Cancer Res 9: 3756-3762.
• Marek M, Kaiser K, Gruber HJ (1997) Biotin-pyrene conjugates with poly(ethylene glycol) spacers are convenient fluorescent probes foe avidin and steptavidin. Bioconjug Chem 8: 560-566. 10.1021/bc970088e.
• Markman M, Mekhail TM (2002) Paclitaxel in cancer therapy. Expert Opin Pharmacother 3: 755-766.doi: 10.1517/14656566.3.6.755.
• McDermott M, Eustace AJ, Busschots S, et al (2014) In vitro Development of chemotherapy and targeted therapy drug-resistant cancer cell lines: a practical guide with case studies. Front Oncol 4: 40. 10.3389/fonc.2014.00040.
• Moley KH, Colditz GA (2016) Effects of obesity on hormonally driven cancer in women. Sci Transl Med 8: 323ps3. 10.1126/scitranslmed.aad8842.
• Nagel CI, Backes FJ, Hade EM, Cohn DE, Eisenhauer EL, O'Malley DM, Fowler JM, Copeland LJ, Salani R (2012) Effect of chemotherapy delays and dose reductions on progression free and overall survival in the treatment of epithelial ovarian cancer. Gynecol Oncol 124: 221-224. 10.1016/j.ygyno.2011.10.003.
• Narvekar M, Xue HY, Eoh JY, Wong HL (2014) Nanocarrier for poorly water-soluble anticancer drugs - barriers of translation and solutions. AAPS PharmSciTech 15: 822–833. 10.1208/s12249-014-0107-x.
• Nishiyama N, Kataoka K (2001) Preparation and characterization of size-controlled polymeric micelle containing cis-dichlorodiammineplatinum(II) in the core. J Control Release 74: 83-94.doi: 10.1016/S0168-3659(01)00314-5.
• Nishiyama N, Kato Y, Sugiyama Y, Kataoka K (2001) Cisplatin-loaded polymer-metal complex micelle with time modulated decaying property as novel drug delivery system. Pharm Res 18: 1035-1104. doi: 10.1023/A:101090891.
• Non (1993) Paclitaxel (taxol) for ovarian cancer. Med Lett Drugs Ther 35: 39-40. 8097551.
• Petrucelli N, Daly MB, Pal T (2016) BRCA1- and BRCA2-Associated hereditary breast and ovarian cancer. Gene Reviews® (Internet). Seattle (WA): University of Washington, Seattle; 1993-2017. Available from:.
• Rao SV, Anderson KW, Bachas LG (1997) Determination of the extent of protein biotinylation by fluorescence binding assay. Bioconjug Chem 8: 94-98. 10.1021/bc960080p.
• Razi S, Ghoncheh M, Mohammadian-Hafshejani A, Aziznejhad H, Mohammadian M, Salehiniya H (2016) The incidence and mortality of ovarian cancer and their relationship with the Human Development Index in Asia. E Cancer Med Sci 10: 628. 10.3332/ecancer.2016.628
• Reedijk J, Lohman PH (1985) Cisplatin: synthesis, antitumour activity and mechanism of action. Pharm Weekbl Sci 7: 173-180.doi: 10.1007/BF02307573.
• Rosen B, Laframboise S, Ferguson S, Dodge J, Bernardini M, Murphy J, Segev Y, Sun P, Narod SA (2014) The impacts of neoadjuvant chemotherapy and of debulking surgery on survival from advanced ovarian cancer. Gynecol Oncol 134: 462-467. 10.1016/j.ygyno.2014.07.004.
• Russell-Jones G, McTavish K, McEwan J, Rice J, Nowotnik D (2004) Vitamin-mediated targeting as a potential mechanism to increase drug uptake by tumors. J Inorg Biochem 98: 1625-1633.doi: 10.1016/j.jinorgbio.2004.07.009.
• Takechi R, Taniguchi A, Ebara S, Fukui T, Watanabe T (2008) Biotin deficiency affects the proliferation of human embryonic palatal mesenchymal cells in culture. J Nutrit 138: 680-684. http://www.ncbi.nlm.nih.gov/pubmed/18356320.
• Tripodo G, Mandracchia D, Collina S, Rui M, Rossi D (2014) New perspectives in cancer therapy: the biotin-antitumor molecule conjugates. Med Chem S1: 004. 10.4172/2161-0444.S1-004
• Wilbur DS, Pathare PM, Hamlin Dk, Buhler KR, Vessella RL (1998) Biotin reagents for antibody pretargeting. 3. Synthesis, radioiodination, and evaluation of biotinylated starburst dendrimers. Bioconjug Chem 9: 813-825. 10.1021/bc980055e.
• Wu Q, Yang Z, Nie Y, Shi Y, Fan D (2014) Multi-drug resistance in cancer chemotherapeutics: Mechanisms and lab approaches. Cancer Lett 347: 159-166. 10.1016/j.canlet.2014.03.013.
• Yang W, Cheng Y, Xu T, Wang X, Wen LP (2009) Targeting cancer cells with biotin dendrimer conjugates. Eur J Med Chem 44: 862-868. 10.1016/j.ejmech.2008.04.021.
• Yap TA, Carden CP, Kaye SB (2009) Beyond chemotherapy: targeted therapies in ovarian cancer. Nat Rev Cancer 9: 167-181. 10.1038/nrc2583.
• Yellepeddi VK, Kumar A, Palakurthi S (2009) Surface modified poly(amido)amine dendrimers as diverse nanomolecules for biomedical applications. Expert Opin Drug Deliv 6: 835-850. 10.1517/17425240903061251.
• Yellepeddi VK, Kumar A, Palakurthi S (2009) Biotinylated poly(amido)amine (PAMAM) dendrimers as carriers for drug delivery to ovarian cancer cells in vitro. Anticancer Res 29: 2933-2943.
• Yellepeddi VK, Vangara KK, Palakurthi S (2013) Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells. J Nanopart Res 15: 1874. 10.1007/s11051-013-1874-0
• Zarchi MK, Rouhi M, Abdolahi AH, Hekmatimoghaddam S (2013) The effect of assisted reproductive technologies on gynecological cancer: report of our experiences and literature review. Int J Biomed Sci 9: 129-134.

Identifiers

DOI

10.18388/abp.2017_2331