Dendrimer-paclitaxel complexes for efficient treatment in ovarian cancer: study on OVCAR-3 and HEK293T cells
The present investigation deal with enhancement the therapeutic effect of Paclitaxel (a potent anticancer drug) by increasing its cellular uptake in cancerous cell with subsequent reduction in its cytotoxic effects.To fulfill the aforesaid purpose the Paclitaxel (PTX)-Biotinylated PAMAM dendrimer complex were prepared using biotinylation method. The primary parameter of Biotinylated PAMAM with terminal HN2 group was evaluated such as degree of biotinylation using HABA assay. The basic integrity of complex was studied using DSC. The Drug loading (DL) and drug release (DR) study of Biotinylated PAMAM dendrimer-PTX complex was 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 complex when compared with pure drug, biotinylated complex and Physical mixture of both. The batch 9 showed the highest DL (12.09 %) and DR (70 %) up to 72 h when compared by changing concentrations of drug and biotinylated complex. The OVCAR-3(cancerous) cells showed more cellular uptake than HEK293T (normal) cells. The statistical data also supports the experimental results obtained.The results obtained from both experimental and statistical evaluation confirms that the biotinylated PAMAM NH2 dendrimer-PTX complex helps not only in increasing cellular uptake but also increases the release up to 72h with reduction in cytotoxicity.
American cancer Society Ovarian cancer detailed guide-ovarian cancer key statistics. www.cancer.org 2011.
Disaia PJ, Creasman WT (1997) Epithelial ovarian cancer : In clinical gycecological oncology. St.Louis,Mosby-year book Inc 282-350.
In longo DL, Kasper DL,Jameson JL et al. (2012) .Eiden,Michael V. “Gynecological Malignancies”, Harrisons principles of internal medicine, 18 th edition, Mc Graw-Hill.
Huang YH, Zugates GT, Peng W et al (2009) Nanoparticles delivered suicide gene therapy effectively reduces ovarian tumor burden in mice. Caner Res 69: 6184-6191. 10.1158/0008-5472.
Agrawal A, Saraf S, Asthana A et al (2008) Ligand based dendritic syatsems for tumor targeting. Int J Pharm 350 (1-2): 3-13. 10.1016/j.ijpharm.2007.09.024
Cannizzaro SM (1998) A novel biotinylated degradable polymer for cell interactive applications. Biotechnol Bioeng 58: 529-535. 10.1002/(SICI)1097-0290(19980605)58
Russel Jones G, Mc Tavish K, Mc Ewan J (2004) Vitamin targeting as a potential mechanism to increase drug uptake by tumors. J Inorg Biochem 98: 1625-1633. 10.1016/j.jinorgbio.2004.07.009
Rao SV, Anderson KW, Bachas LG (1997) Determination of extent of protein biotinylation by fluorescence binding assay. Bioconjug Chem 8: 94-98. 10.1021/bc960080p.
Yang W, Cheng Y, Xu T, Wang X, Wen LP (2009) Targeting cancer cells with biotin dendrimer conjugates. Eur J Med Chem 44(2): 862-868. 10.1016/j.ejmech.2008.04.021.
Kesharwani P, Iyer AK (2015) Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery. Drug discovery today 20(5):536-547. doi:10.1016/j.drudis.2014.12.012.
Marek M, Kaiser K, Gruber HJ (1997) Biotinepyrene conjugates with poly(ethylene glycol) spacers are convenient fluorescent probes foe avidin and steptavidin. Bioconjug Chem. 8: 560-566. 10.1021/bc970088e.
Non (1993) Paclitaxel (taxol) for ovarian cancer. Med let drugs. Ther 35(896):39-40. 8097551.
Mamede M, Saga T, Kobayashi H, Ishimori T et al (2003) Radiolabelling of avidin with very high specific activity for internal radiation therapy of intraperitoneally disseminated tumors. Clin cancer research 9: 3756-3762.
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 (8):1874. 10.1007/s11051-013-1874-0.
Yellepeddi VK, Kumar A, Palakurthi S (2009) Surface modified poly(amino)amine dendrimers as diverse nanomolecules for biomedical applications. Expert opinion drug delivery 6: 835-850. 10.1517/17425240903061251.
Majoros IJ, Myc A, Thomas T, Mehta CB and Baker JR Jr (2006) PAMAM dendrimer-based multifunctional conjugate for cancer therapy: synthesis, characterization, and functionality. Biomacromolecules 7: 572-579. 10.1021/bm0506142.
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 (6): 910-917. 10.1021/bc0000583.
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(6): 813-825. 10.1021/bc980055e.
Kirkpatrick GJ, Plumb JA, Sutcliffe OB, Flint DJ, Wheate NJ (2011) Evaluation of anionic haf generation poly(amidiamine) dendrimers as delivery vehicle for active component of anticancer drug cisplatin. J Inorg Biochem 105 (9): 1115-1122. 10.1016/j.jinorgbio.2011.05.017.
Reedijk J, Lohman PH (1985) Cisplatin: synthesis, antitumor activity and mechanism of action. Pharn Weekbl Sci 7(5): 173-180. https://doi.org/10.1007/BF02307573.
Nishiyama N, Kataoka K (2001) Preparation and characterization of size-controlled polymeric micelle containing cis-dichlorodiammineplatinum(II) in the core. J Control Release 74(1-3): 83-94. https://doi.org/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 (7): 1035-104. https://doi.org/10.1023/A:101090891.
Acta Biochimica Polonica is an open access quarterly and publishes four issues a year. All contents are distributed under the Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) license. Everybody may use the content following terms: Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made, ShareAlike — If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original. There are no additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Copyright for all published papers © stays with the authors.
Copyright for the journal: © Polish Biochemical Society.