Abstract
Macromolecular systems with well-defined sizes, shapes and high controlled architecture like dendrimers are of eminent interest in nanomedical applications such as drug delivery, gene transfection, and imaging. In this paper versatile protocols for the synthesis of polyester-based, hydrolysable, polycationic dendrimers have been setup. Fourth and fifth generation dendrimers equipped with several peripheral hydroxyl groups were prepared from 2, 2-bis(hydroxymethyl)propanoic acid. They were successfully esterified with arginine alone or mixed with lysine or O-methyltyrosine and with dipeptide arginine-glycine and seven polycationic dendrimers were finally obtained as hydrochlorides. Their structures and composition were confirmed by NMR analysis and by experimental molecular weight computed by volumetric titration and their buffer capacity was higher than fourth generation polyamidoamine (G4- PAMAM) derivatives taken as reference. The synthesized dendrimers harmonize a polycationic character and a buffer capacity which presuppose a good transfection efficiency with a degradable scaffold thus appearing as a promising team of new non-toxic vectors for biomedical applications.
Article PDF
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
References
R. Hourani and A. Kakkar, Macromol. Rapid Commun., 31, 947 (2010).
M. Sowinska and Z. Urbanczyk-Lipkowska, New J. Chem., 38, 2168 (2014).
P. Kesharwani, K. Jain, and N. Jain, Progr. Polym. Sci., 39, 268 (2014).
J. Datija, V. V. R. Sai, and S. Mukherji, S. J. Mater. Chem., 21, 14367 (2011).
A.-M. Caminade, in Dendrimers: Towards Catalytic, Material and Biomedical Uses, A-M. Caminade, C-O. Turrin, R. Laurent, A. Ouali, and B. Delavaux-Nicot, Eds., John Wiley & Sons Ltd, Chichester, UK., 2011, Ch. 15, pp 375–392.
J.-H. Kim, K. Park, H. Y. Nam, S. Lee, K. Kim, and I. C. Kwon, Progr. Polym. Sci., 32, 1031 (2007).
Z. Wang, G. Niu, and X. Chen, Pharm. Res., 31, 1358 (2014).
C. Dufès, I. F. Uchegbu, and A. G. Schätzlein, Adv. Drug Deliv. Rev., 57, 2177 (2005).
H. Eliyahu, Y. Barenholz, and A. Domb, Molecules, 10, 34 (2005).
D. W. Pack, A. S. Hoffman, S. Pun, and P. S. Stayton, Nat. Rev. Drug Disc., 4, 581 (2005).
D. Schaffert and E. Wagner, Gene Ther., 15, 1131 (2008).
M. A. Mintzer and E. E. Simanek, Chem. Rev., 109, 259 (2009).
S. O’Rorke, M. Keeney, and A. Pandit, Progr. Polym. Sci., 35, 441 (2010).
H._M. Marvaniya, P. K: Parikh, V. R. Patel, K. N. Modi, and D. J. Sen, J. Chem. Pharm. Res., 2, 97 (2010).
X. Guo and L. Huang, Acc. Chem. Res., 45, 971 (2012).
Y. Yue and C. Wu, Biomater. Sci., 1, 152 (2013).
S. Biswas and V. P. Torchilin, Pharmaceuticals, 6, 161 (2013).
N. Taghavi Pourianazar, P. Mutulu, and U. Gunduz, J. Nanopart. Res., 16, 2342/1 (2014).
G. R. Newkome, and C. D. Shreiner, Polymer, 49, 1 (2008).
J. D. Eichman, A. S. U. Bielinska, J. F. Kukowska-Latallo, and J. R. Baker Jr., Sci. Technol. Today, 3, 232 (2000).
H. Zong, D. Shah, K. Selwa, R. E. Tsuchida, R. Rattan, J. Mohan, A. B. Stein, J. B. Otis, and S. N. Goonewardena, Chem. Open, 4, 335 (2015).
L. Han, R. Huang, S. Liu, S. Huang, and C. Jiang, Mol. Pharm., 7, 2156 (2010).
Y. Gao, Z. Li, X. Xie, C. Wnaga, J. You, F. Moa, B. Jin, J. Chen, J. Shao, H. Chen, and L. Jia, Eur. J. Pharm. Sci., 70, 55 (2015).
Y. Zhang, T. P. Thomas, K-H. Lee, M. Li, H. Zong, A. M. Desai, A. Kotlyar, B. Huang, H. M. M. Banaszak, and J. R. Baker Jr., Bioorg. Med. Chem., 19, 2557 (2011).
S. L. Mekuria, T. A. Debele, H-Y. Chou, and H-C. Tsai, J. Phys. Chem. B, 120, 123 (2016).
R. B. Kolhatkar, K. M. Kitchens, P. W. Swaan, and H. Ghandehari, Bioconj. Chem., 18, 2054 (2007).
C. L. Waite, S. M. Sparks, K. E. Uhrich, and C. M. Roth, BMC Biotechnol., 9, 9 (2009).
L. Jianfeng, L. Jinjian, C. Liping, T. Lingling, G. Hongjun, Y. Cuihong, W. Dezhi, S. Linqi, K. Deling, and L. Zongjin, J. Nanosci. Nanotechnol., 14, 3305 (2014).
M. Ciolkowski, J. F. Petersen, M. Ficker, A. Janaszewska, J. B. Christensen, B. Klajnert, and M. Bryszewska, Nanomed-Nanotechnol., 8, 815 (2012).
A. Ghilardi, D. Pezzoli, M. C. Bellucci, C. Malloggi, A. Negri, A. Sgnappa, G. Tedeschi, G. Candiani, and A. Volonterio, Bioconjug. Chem., 24, 1928 (2013).
H. Arima, K. Motoyama, and T. Higashi, Adv. Drug Deliv. Rev., 65, 1204 (2013).
R. S. Navath, A. R. Menjoge, B. Wang, R. Romero, S. Kannan, and R. M. Kannan, Biomacromolecules, 11, 1544 (2010).
J. H. Park, J-S. Park, and J. S. Choi, Macromol. Res., 22, 500 (2014).
F. Wang, Y. Wang, H. Wang, N. Shao, Y. Chen, and Y. Cheng, Biomaterials, 35, 9187 (2014).
S. J. Lam, A. Sulistio, K. Ladewig, E. H. H. Wong, A. Blencowe, and G. G. Qiao, Austr. J. Chem., 67, 592 (2014).
H. Y. Nam, K. Nam, H. J. Hahn, B. H. Kim, H. J. Lim, H. J. Kim, J. S. Choi, and J. S. Park, Biomaterials, 30, 665 (2009).
M. Liu, J. Chen, Y-N. Xue, W-M. Liu, R-X. Zhuo, and S-W. Huang, Bioconjug. Chem., 20, 2317 (2009).
Q. A. A. Eltoukhy, D. J. Siegwart, C. A. Alabi, J. S. Rajan, R. Langer, and D. G. Anderson, Biomaterials, 33, 3594 (2012).
C. J. Bishop, T-M. Ketola, S. Y. Tzeng, J. C. Sunshine, A. Urttio, H. Lemmetyinen, E. Vuorimaa-Laukkanen, M. Yliperttula, and J. J. Green, J. Am. Chem. Soc., 135, 6951 (2013).
K. L. Chang, Y. Higuchi, S. Kawakami, F. Yamashita, and M. Hashida, J. Control. Release, 156, 195 (2011).
Y. Wen, Z. Guo, Z. Du, R. Fang, H. Wu, X. Zeng, C. Wang, M. Feng, and S. Pan, Biomaterials, 33, 8111 (2012).
F. Wang, Y. Wang, H. Wang, N. Shao, Y. Chen, and Y. Cheng, Biomaterials, 35, 9187 (2014).
J. Shi, J. G. Schellinger, R. N. Johnson, J. L. Choi, B. Chou, E. L. Anghel, and S. H. Pun, Biomacromolecules, 14, 1961 (2013).
I. Nakase, H. Akita, K. Kogure, A. Gräslund, Ü. Langel, H. Harashima, and S. Futaki, Acc. Chem. Res., 45, 1132 (2012).
I. Nakase, G. Tanaka, and S. Futaki, Mol. Bio Syst., 9, 855 (2013).
C. Liu, X. Liu, P. Rocchi, F. Qu, J. L. Iovanna, and L. Peng, Bioconjug. Chem., 25, 521 (2014).
X. Liu, C. Liu, J. Zhou, C. Chen, F. Qu, J. J. Rossi, P. Rocchi, and L. Peng, Nanoscale, 7, 3867 (2015).
J. B. Kim, J. S. Choi, K. Nam, M. Lee, J. S. Park, and J. K. Lee, J. Control. Release, 114, 110 (2006).
T. Kim, C. Z. Bai, K. Nam, and J. Park, J. Control. Release, 136, 132 (2009).
Q. Peng, J. Zhu, Y. Yu, L. Hoffman, and X. Yang, J. Biomater. Sci. Polym. Ed., 26, 1163 (2015).
A. Carlmark, E. Malstrӧm, and M. Malkoch, Chem. Soc. Rev., 42, 5858 (2013).
N. Feliu, M. V. Walter, M. I. Montañez, A. Kunzmann, A. Hult, A. Nyström, M. Malkoch, and B. Fadeel, Biomaterials, 33, 1970 (2012).
J. S. Moore and S. I. Stupp, Macromolecules, 23, 65 (1990).
H. Ihre, A. Hult, J. M. J Fréchet, and I. Gitsov, Macromolecules, 31, 4061 (1998).
M. Zhao, J. Liu, X. Zhang, L. Peng, C. Li, and S. Peng, Bioorg. Med. Chem., 17, 3680 (2009).
A. I. Vogel, in Elementary Practical Organic Chemistry. Part III. Quantitative Organic Analysis, Longman Ed., 1st ed., London, 1958, Ch. 20, p 702.
F. Von Seel, in Grundlagen der Analytischen Chemie, G. Geier, Ed., 5th ed., Verlag Chemie, Weinheim, 1970, Vol. 82, p 962.
L. Aravindana, K. A. Bicknell, G. Brooks, V. V. Khutoryanskiya, and A. C. Williams, Int. J. Pharm., 378, 201 (2009).
J. M. Benns, J. S. Choi, R. I. Mahato, J. S. Park, and S. W. Kim, Bioconjug. Chem., 11, 637 (2000).
J. Yang, Q. Zhang, H. Chang, and Y. Cheng, Chem. Rev., 115, 5274 (2015).
H. Kessler and M. Molter, J. Am. Chem. Soc., 98, 5969 (1976).
S. Y. Gwang, M. B. Yun, C. Hye, K. Bokyung, S. C. Insung, and S. C. Joon, Bioconjug. Chem., 22, 1046 (2011).
N. Heigl, S. Bachmann, C. H. Petter, M. Marchetti-Deschmann, G. Allmaier, G. K. Bonn, and C. W. Huck, Anal. Chem., 81, 5655 (2009).
Y. Zeng, Y. Kurokawa, T. T. Win-Shwe, Q. Zeng, S. Hirano, Z. Zhang, and H. Sone, J. Toxicol. Sci., 41, 351 (2016).
Author information
Authors and Affiliations
Corresponding author
Additional information
Acknowledgments: This work has been supported by University of Genoa (Progetti di Ateneo). The authors are very thankful to Dr Gaby Brice Taptue for language help and to Mr Gagliardo Osvaldo for Elemental analysis.
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Alfei, S., Castellaro, S. Synthesis and characterization of polyester-based dendrimers containing peripheral arginine or mixed amino acids as potential vectors for gene and drug delivery. Macromol. Res. 25, 1172–1186 (2017). https://doi.org/10.1007/s13233-017-5160-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13233-017-5160-3