Polyamidoamine-Drug Conjugates Containing Metal-Based Anticancer Compounds
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Polyamidoamine drug conjugates containing ferrocene and platinum analogues were prepared in this study. Fourier transform infrared spectra confirmed the successful isolation of the conjugates with signals at 3300 cm−1 for amide N–H stretch and for C=O stretch at 1655–1635 cm−1 resulting from the conjugation of 4-ferrocenylketobutanoic acid. The polyamidoamine drug conjugate particle size was 247.1 nm and 258.3 nm suggesting their ability to exhibit in vitro phagocytosis. The average particle charges were 29 and 30.2, which was indicative of good stability and the capability to resist aggregation. In vitro cytotoxicity studies further revealed that the conjugates 1–5 did not exhibit cytotoxicity towards the normal cell lines (EA.hy926) whereas high cytotoxic activity was noted against the cancer cell lines (MCF-7 and MDA-MB-231) indicating selectivity towards cancer cell lines. Fc-PDA acted as a potentiating agent when incorporated together with DACH PtCl2 in the polymers, resulting in a good inhibitory effect in vitro. However, when combining Fc-PDA with K2PtCl4 in the polymer, an antagonistic effect was noted. The current findings implicate that the prepared conjugates hold the potential as therapeutics for the treatment of breast cancer. Further research is required to confirm this.
KeywordsAnticancer Cytotoxicity Drug delivery Ferrocene Platinum Polyamidoamine Polymer-conjugate
Financial support received from the Medical Research Council (Self-Initiated Research) and National Research Foundation, South Africa to carry out this research is gratefully acknowledged.
Compliance with Ethical Standards
Conflict of interest
The authors declare no conflicts of interest.
- 1.World Health Organisation (2017) Cancer, Media Centre. http://www.who.int/mediacentre/factsheets/fs297/en/. Accessed 14 May 2017
- 13.P. Wu, H. Chen, R. Jin, T. Weng, J.K. Ho, C. You, L. Zhang, X. Wang, C. Han, Non-viral gene delivery systems for tissue repair and regeneration. J. Transl. Med. 16, 1–20 (2018)Google Scholar
- 32.Hydrotrope Promoted Aza-Michael Addition Reaction. Chapter 6, pages 206–228. https://shodhganga.inflibnet.ac.in/bitstream/10603/25448/12/12_chapter_06.pdf. Accessed 22 Aug 2019
- 40.A.K. Biswas, M.R. Islam, Z.S. Choudhury, A. Mostafa, M.F. Kadir, Nanotechnology based approaches in cancer therapeutics. Adv. Nat. Sci. 5, 043001 (2014)Google Scholar
- 41.A. Rodzinski, R. Guduru, E. Stimphil, T. Stewart, P. Liang, C. Runowicz, S. Khizroev. Targeted, controlled anticancer drug delivery and release with magnetoelectric nanoparticles, Proceedings of the 107th Annual Meeting of the American Association for Cancer Research Apr 16–20, New Orleans, LA. Philadelphia (PA): AACR Cancer Res 76 (14 Suppl), Abstract no 2204 (2016)Google Scholar
- 44.R. Patil, J. Portilla-Arias, H. Ding, B. Konda, A. Rekechenetskiy, S. Inoue, K.L. Black, E. Holler, J.Y. Ljubimova, Cellular delivery of doxorubicin via pH-controlled hydrazone linkage using multifunctional nano vehicle based on poly (β-L-malic acid). Int. J. Mol. Sci. 13, 11681–11693 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
- 47.S. Honary, F. Zahir, Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 2). Trop. J. Pharm. Res. 12, 265–273 (2013)Google Scholar
- 49.R.S. Shula, Z. Chen, K. Cheng, Strategies of drug delivery, in Advanced Drug Delivery, ed. by A.K. Mitra, C.H. Lee, K. Cheng (Wiley, New Jersey, 2015)Google Scholar
- 51.M.J. Johnston, S.C. Semple, S.K. Klimuk, K. Edwards, M.L. Eisenhardt, E.C. Leng, G. Karlsson, D. Correctyanko, P.R. Cullis, Therapeutically optimized rates of drug release can be achieved by varying the drug-to-lipid ratio in liposomal vincristine formulations. Biochim. Biophys. Acta. 1758, 55–64 (2006)CrossRefPubMedGoogle Scholar
- 54.H.S. Oberoi, N.V. Nukolova, Y. Zhao, S.M. Cohen, A.V. Kabanov, T.K. Bronich, Preparation and in vivo evaluation of dichloro (1,2-diaminocyclohexane) platinum (II)-loaded core cross-linked polymer micelles. Chemother. Res. Pract. (2012). https://doi.org/10.1155/2012/905796 CrossRefPubMedPubMedCentralGoogle Scholar
- 56.E.W. Neuse, G. Caldwell, A.G. Perlwitz, Cis-diaminedichloroplatinum(II) complexes reversibly bound to water-soluble polyaspartamide carriers for chemotherapeutic applications. 2. Platinum coordination to ethylenediamine ligands attached to poly(ethylene oxide)-grafted carrier polymers. J. Inorg. Organomet. Polym. 5, 195–207 (1995)CrossRefGoogle Scholar