Synthesis of Water-soluble, Polyester-based Dendrimer Prodrugs for Exploiting Therapeutic Properties of Two Triterpenoid Acids

Silvana Alfei; Gaby Brice Taptue; Silvia Catena; Angela Bisio

doi:10.1007/s10118-018-2124-9

Your Location：

Home >

Browse articles >

Synthesis of Water-soluble, Polyester-based Dendrimer Prodrugs for Exploiting Therapeutic Properties of Two Triterpenoid Acids

ARTICLE | Updated：2021-02-18

- Synthesis of Water-soluble, Polyester-based Dendrimer Prodrugs for Exploiting Therapeutic Properties of Two Triterpenoid Acids
- Synthesis of Water-soluble, Polyester-based Dendrimer Prodrugs for Exploiting Therapeutic Properties of Two Triterpenoid Acids
- Chinese Journal of Polymer Science 2018年36卷第9期页码：999-1010
- Affiliations：
  
  Dipartimento di Farmacia, Sezione di Chimica e Tecnologie Farmaceutiche e Alimentari, Università di Genova, Viale Cembrano 4, I-16148 Genova, Italy
- Author bio：
  
  alfei@difar.unige.it
- Funds：
  
  The authors are very thankful to Mr Gagliardo Osvaldo for Elemental Analysis and to University of Genova.
- DOI：10.1007/s10118-018-2124-9
  中图分类号：
- 收稿：2017-12-15，
  
  修回：2017-12-15，
  
  录用：2018-2-7，
  
  网络首发：2018-03-28，
  
  纸质出版：2018-09
- Accepted：
Scan QR Code
Silvana Alfei, Gaby Brice Taptue, Silvia Catena, 等. Synthesis of Water-soluble, Polyester-based Dendrimer Prodrugs for Exploiting Therapeutic Properties of Two Triterpenoid Acids[J]. Chinese Journal of Polymer Science, 2018,36(9):999-1010.

Silvana Alfei, Gaby Brice Taptue, Silvia Catena, et al. Synthesis of Water-soluble, Polyester-based Dendrimer Prodrugs for Exploiting Therapeutic Properties of Two Triterpenoid Acids[J]. Chinese Journal of Polymer Science, 2018, 36(9): 999-1010.
Silvana Alfei, Gaby Brice Taptue, Silvia Catena, 等. Synthesis of Water-soluble, Polyester-based Dendrimer Prodrugs for Exploiting Therapeutic Properties of Two Triterpenoid Acids[J]. Chinese Journal of Polymer Science, 2018,36(9):999-1010. DOI： 10.1007/s10118-018-2124-9.

Silvana Alfei, Gaby Brice Taptue, Silvia Catena, et al. Synthesis of Water-soluble, Polyester-based Dendrimer Prodrugs for Exploiting Therapeutic Properties of Two Triterpenoid Acids[J]. Chinese Journal of Polymer Science, 2018, 36(9): 999-1010. DOI： 10.1007/s10118-018-2124-9.

摘要

Abstract

Dendrimers are macromolecules characterized by high controlled size

shape and architecture

presence of inner cavities able to accommodate small molecules and many peripheral functional groups to bind target entities. They are of eminent interest for biomedical applications

including gene transfection

tissue engineering

imaging

and drug delivery. The well-known pharmacological activities of ursolic and oleanolic acids are limited by their small water solubility

non-specific cell distribution

low bioavailability

poor pharmacokinetics

and their direct administration could result in the release of thrombi. To overcome such problems

in this paper we described their physical incorporation inside amino acids-modified polyester-based dendrimers which made them highly water-soluble. IR

NMR

zeta potential

mean size of particles

buffer capacity and drug release profiles of prepared materials were reported. The achieved water-soluble complexes harmonize a polycationic character and a buffer capacity which presuppose efficient cell penetration and increased residence time with a biodegradable cell respectful scaffold

thus appearing as a promising team of not toxic prodrugs for safe administration of ursolic and oleanolic acids.

关键词

Keywords

references

Hourani, R.; Kakkar, A . Advances in the elegance of chemistry in designing dendrimers . Macromol. Rapid Commun. , 2010 . 31 947 - 974 . DOI: 10.1002/marc.200900712 http://doi.org/10.1002/marc.200900712 .

Sowinska, M.; Urbanczyk-Lipkowska, Z . Advances in the chemistry of dendrimers . New J. Chem. , 2014 . 38 2168 - 2203 . DOI: 10.1039/c3nj01239e http://doi.org/10.1039/c3nj01239e .

Madaan, K.; Kumar, S.; Poonia, N.; Lather, V.; Pandita, D . Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues . J. Pharm. Bioall. Sci. , 2014 . 6 139 - 150 . DOI: 10.4103/0975-7406.130965 http://doi.org/10.4103/0975-7406.130965 .

Hu, X. L.; Liu, G. H.; Li, Y.; Wang, X. R.; Liu, S. Y . Cell-penetrating hyperbranched polyprodrug amphiphiles for synergistic reductive milieu-triggered drug release and enhanced magnetic resonance signals . J. Am. Chem. Soc. , 2015 . 137 362 - 368 . DOI: 10.1021/ja5105848 http://doi.org/10.1021/ja5105848 .

Li, X.; Qian, Y.; Liu, T.; Hu, X.; Zhang, G.; You, Y.; Liu, S . Amphiphilic multiarm star block copolymer-based multifunctional unimolecular micelles for cancer targeted drug delivery and MR imaging . Biomaterials , 2011 . 32 6595 - 605 . DOI: 10.1016/j.biomaterials.2011.05.049. http://doi.org/10.1016/j.biomaterials.2011.05.049. .

Xu, J.; Luo, S. Z.; Shi, W. F.; Liu, S. Y . Two-stage collapse of unimolecular micelles with double thermoresponsive coronas . Langmuir , 2006 . 22 989 - 997 . DOI: 10.1021/la0522707 http://doi.org/10.1021/la0522707 .

Luo, S. Z.; Xu, J.; Zhu, Z. Y.; Wu, C.; Liu, S. Y . Phase transition behavior of unimolecular micelles with thermoresponsive poly(N-isopropylacrylamide) coronas . J. Physic. Chem. , 2006 . 110 9132 - 9139 . DOI: 10.1021/jp061055b http://doi.org/10.1021/jp061055b .

Xu, H. X.; Xu, J.; Jiang, X. Z.; Zhu, Z. Y.; Rao, J. Y.; Yin, J.; Wu, T.; Liu, H. W.; Liu, S. Y . Thermosensitive unimolecular micelles surface-decorated with gold nanoparticles of tunable spatial distribution . Chem. Mater. , 2007 . 19 2489 - 2494 . DOI: 10.1021/cm070088g http://doi.org/10.1021/cm070088g .

Luo, S.; Hu, X.; Ling, C.; Liu, X.; Chen, S.; Han, M . Multiarm star-like unimolecular micelles with a dendritic core and a dual thermosensitive shell . Polym. Int. , 2011 . 60 717 - 724 . DOI: 10.1002/pi.2989 http://doi.org/10.1002/pi.2989 .

Kesharwani, P.; Jain, K.; Jain, N . Dendrimer as nanocarrier for drug delivery . Prog. Polym. Sci. , 2014 . 39 268 - 307 . DOI: 10.1016/j.progpolymsci.2013.07.005 http://doi.org/10.1016/j.progpolymsci.2013.07.005 .

Datija, J.; Sai, V. V. R.; Mukherji, S . Dendrimers in biosensors: concept and applications . J. Mater. Chem. , 2011 . 21 14367 - 14386 . DOI: 10.1039/c1jm10527b http://doi.org/10.1039/c1jm10527b .

Caminade, A M. in " Dendrimers: towards catalytic, material and biomedical uses, Chapter 15”, ed. By Caminade, A. M.; Turrin, C. O.; Laurent, R.; Ouali, A.; Delavaux-Nicot, B. John Wiley & Sons, Chichester, UK., 2011, p. 375–392.

Kim, J. H.; Park, K.; Nam, H. Y., Lee, S.; Kim, K.; Kwon, I. C. Polymers for bioimaging. Prog. Polym. Sci. 2007, 32, 1031-1053.

Wang, Z.; Niu, G.; Chen, X . Polymeric materials for theranostic applications . Pharm. Res. , 2014 . 31 1358 - 1376 . DOI: 10.1007/s11095-013-1103-7 http://doi.org/10.1007/s11095-013-1103-7 .

Dufès, C.; Uchegbu, I. F.; Schätzlein, A. G . Dendrimers in gene delivery . Adv. Drug Deliver. Rev. , 2005 . 57 2177 - 2202 . DOI: 10.1016/j.addr.2005.09.017 http://doi.org/10.1016/j.addr.2005.09.017 .

Eliyahu, H.; Barenholz, Y.; Domb, A. J . Polymers for DNA delivery . Molecules , 2005 . 10 34 - 64 . DOI: 10.3390/10010034 http://doi.org/10.3390/10010034 .

Pack, D. W.; Hoffman, A. S.; Pun, S.; Stayton, P. S . Design and development of polymers for gene delivery . Nat. Rev. Drug Discov. , 2005 . 4 581 - 593 . DOI: 10.1038/nrd1775 http://doi.org/10.1038/nrd1775 .

Schaffert, D.; Wagner, E . Gene therapy progress and prospects: synthetic polymer-based systems . Gene Ther. , 2008 . 15 1131 - 1138 . DOI: 10.1038/gt.2008.105 http://doi.org/10.1038/gt.2008.105 .

Mintzer, M. A.; Simanek, E. E . Nonviral vectors for gene delivery . Chem. Rev. , 2009 . 109 259 - 302 . DOI: 10.1021/cr800409e http://doi.org/10.1021/cr800409e .

O’Rorke, S.; Keeney, M.; Pandit, A . Non-viral polyplexes: scaffold mediated delivery for gene therapy . Prog. Polym. Sci. , 2010 . 35 441 - 458 . DOI: 10.1016/j.progpolymsci.2010.01.005 http://doi.org/10.1016/j.progpolymsci.2010.01.005 .

Marvaniya, H. M.; Parikh, P. K.; Patel, V. R.; Modi, K. N.; Sen, D. J . Dendrimer nanocarriers as versatile vectors in gene delivery . J. Chem. Pharm. Res. , 2010 . 2 97 - 108 . .

Guo, X.; Huang, L . Recent advances in nonviral vectors for gene delivery . Acc. Chem. Res. , 2012 . 45 971 - 979 . DOI: 10.1021/ar200151m http://doi.org/10.1021/ar200151m .

Yue, Y.; Wu, C . Progress and perspectives in developing polymeric vectors for in vitro gene delivery . Biomater. Sci. , 2013 . 1 152 - 170 . DOI: 10.1039/C2BM00030J http://doi.org/10.1039/C2BM00030J .

Biswas, S.; Torchilin, V. P . Dendrimers for siRNA delivery . Pharmaceuticals , 2013 . 6 161 - 183 . DOI: 10.3390/ph6020161 http://doi.org/10.3390/ph6020161 .

Pourianazar, N. T.; Mutulu, P.; Gunduz, U . Bioapplications of poly(amidoamine) (PAMAM) dendrimers in nanomedicine . J. Nanopart. Res. , 2014 . 16 2342/1 - 2342/38 . .

Newkome, G. R.; Shreiner, C. D . Poly(amidoamine), polypropylenimine, and related dendrimers and dendrons possessing different 1→2 branching motifs: An overview of the divergent procedures . Polymer , 2008 . 49 1 - 173 . DOI: 10.1016/j.polymer.2007.10.021 http://doi.org/10.1016/j.polymer.2007.10.021 .

Eichman, J. D.; Bielinska, A. U.; Kukowska-Latallo, J. F.; Baker Jr, J. R . The use of PAMAM dendrimers in the efficient transfer of genetic material into cells . Sci. Technol. Today , 2000 . 3 232 - 245 . DOI: 10.1016/S1461-5347(00)00273-X http://doi.org/10.1016/S1461-5347(00)00273-X .

Zong, H.; Shah, D.; Selwa, K.; Tsuchida, R. E.; Rattan, R.; Mohan, J.; Stein, A. B.; Otis, J. B.; Goonewardena, S. N . Design and evaluation of tumor-specific dendrimer epigenetic therapeutics chemistryopen . Chem. Open , 2015 . 4 335 - 341 . .

Han, L.; Huang, R.; Liu, S.; Huang, S.; Jiang, C . Peptide-conjugated PAMAM for targeted doxorubicin delivery to transferrin receptor overexpressed tumors . Mol. Pharm. , 2010 . 7 2156 - 2165 . DOI: 10.1021/mp100185f http://doi.org/10.1021/mp100185f .

Gao, Y.; Li, Z.; Xie, X.; Wang, C.; You, J.; Mo, F.; Jin, B.; Chen, J.; Shao, J.; Chen, H.; Jia, L . Dendrimeric anticancer prodrugs for targeted delivery of ursolic acid to folate receptor-expressing cancer cells: synthesis and biological evaluation . Eur. J. Pharm. Sci. , 2015 . 70 55 - 63 . DOI: 10.1016/j.ejps.2015.01.007 http://doi.org/10.1016/j.ejps.2015.01.007 .

Zhang, Y.; Thomas, T. P.; Lee, K. H.; Li, M.; Zong, H.; Desai, A. M.; Kotlyar, A.; Huang, B.; Banaszak H. M. M.; Baker, J. R. Jr . Polyvalent saccharide-functionalized generation 3 poly(amidoamine) dendrimer-methotrexate conjugate as a potential anticancer agent . Bioorg. Med. Chem. , 2011 . 19 2557 - 2564 . DOI: 10.1016/j.bmc.2011.03.019 http://doi.org/10.1016/j.bmc.2011.03.019 .

Mekuria, S. L.; Debele, T. A.; Chou, H Y.; Tsai, H C . IL-6 antibody and RGD peptide conjugated poly(amidoamine) dendrimer for targeted drug delivery of HeLa cells . J. Phys. Chem. B , 2016 . 120 123 - 130 . DOI: 10.1021/acs.jpcb.5b11125 http://doi.org/10.1021/acs.jpcb.5b11125 .

Kolhatkar, R. B.; Kitchens, K. M.; Swaan, P. W.; Ghandehari, H . Surface acetylation of polyamidoamine (PAMAM) dendrimers decreases cytotoxicity while maintaining membrane permeability . Bioconj. Chem. , 2007 . 18 2054 - 2060 . DOI: 10.1021/bc0603889 http://doi.org/10.1021/bc0603889 .

Waite, C. L.; Sparks, S. M.; Uhrich, K. E.; Roth, C. M . Acetylation of PAMAM dendrimers for cellular delivery of siRNA . BMC Biotechnol. , 2009 . 9 9 - 38 . DOI: 10.1186/1472-6750-9-9 http://doi.org/10.1186/1472-6750-9-9 .

Liu, J. F.; Liu, J. J.; Chu, L. P.; Tong, L. L.; Gao, H. J.; Yang, C. H.; Wang, D. Z.; Shi, L. Q.; Kung, D. L.; Li, Z. J . Synthesis, biodistribution, and imaging of PEGylated-acetylated polyamidoamine dendrimers . J. Nanosci. Nanotechnol. , 2014 . 14 3305 - 3312 . DOI: 10.1166/jnn.2014.7995 http://doi.org/10.1166/jnn.2014.7995 .

Ciolkowski, M.; Petersen, J. F.; Ficker, M.; Janaszewska, A.; Christensen, J. B.; Klajnert, B.; Bryszewska, M . Surface modifi-cation of PAMAM dendrimer improves its biocompatibility . Nanomed. Nanotechnol. , 2012 . 8 815 - 817 . DOI: 10.1016/j.nano.2012.03.009 http://doi.org/10.1016/j.nano.2012.03.009 .

Ghilardi, A.; Pezzoli, D.; Bellucci, M. C.; Malloggi, C.; Negri, A.; Sgnappa, A.; Tedeschi, G.; Candiani, G.; Volonterio, A . Synthesis of multifunctional PAMAM-aminoglycoside conjugates with enhanced transfection efficiency . Bioconj. Chem. , 2013 . 24 1928 - 1963 . DOI: 10.1021/bc4003635 http://doi.org/10.1021/bc4003635 .

Arima, H.; Motoyama, K.; Higashi, T . Sugar-appended polyamidoamine dendrimer conjugates with cyclodextrins as cell-specific non-viral vectors . Adv. Drug Deliver. Rev. , 2013 . 65 1204 - 1214 . DOI: 10.1016/j.addr.2013.04.001 http://doi.org/10.1016/j.addr.2013.04.001 .

Navath, R. S. Menjoge, A. R.; Wang, B.; Romero, R.; Kannan, S.; Kannan, R. M . Amino acid-functionalized dendrimers with heterobifunctional chemoselective peripheral groups for drug delivery applications . Biomacromolecules , 2010 . 11 1544 - 1536 . DOI: 10.1021/bm100186b http://doi.org/10.1021/bm100186b .

Park, J. H.; Park, J. S.; Choi, J. S . Basic amino acid-conjugated polyamidoamine dendrimers with enhanced gene transfection efficiency . Macromol. Res. , 2014 . 22 500 - 508 . DOI: 10.1007/s13233-014-2073-2 http://doi.org/10.1007/s13233-014-2073-2 .

Wang, F.; Wang, Y.; Wang, H.; Shao, N.; Chen, Y.; Cheng, Y . Synergistic effect of amino acids modified on dendrimer surface in gene delivery . Biomaterials , 2014 . 35 9187 - 9198 . DOI: 10.1016/j.biomaterials.2014.07.027 http://doi.org/10.1016/j.biomaterials.2014.07.027 .

Lam, S. J.; Sulistio, A.; Ladewig, K.; Wong, E. H. H.; Blencowe, A.; Qiao, G. G . Peptide-based star polymers as potential siRNA carriers . Austr. J. Chem. , 2014 . 67 592 - 597 . DOI: 10.1071/CH13525 http://doi.org/10.1071/CH13525 .

Nam, H. Y.; Nam, K.; Hahn, H. J.; Kim, B. H.; Lim, H. J.; Kim, H. J.; Choi, J. S.; Park, J. S . Biodegradable PAMAM ester for enhanced transfection efficiency with low cytotoxicity . Biomaterials , 2009 . 30 665 - 673 . DOI: 10.1016/j.biomaterials.2008.10.013 http://doi.org/10.1016/j.biomaterials.2008.10.013 .

Liu, M.; Chen, J.; Xue, Y. N.; Liu, W. M.; Zhuo, R. X.; Huang, S. W . Poly(beta-aminoester)s with pendant primary amines for efficient gene delivery . Bioconj. Chem , 2009 . 20 2317 - 2323 . DOI: 10.1021/bc900317m http://doi.org/10.1021/bc900317m .

Eltoukhy, Q . Effect of molecular weight of amine end-modified poly(β-amino ester)s on gene delivery efficiency and toxicity . Biomaterials , 2012 . 33 3594 - 3603 . DOI: 10.1016/j.biomaterials.2012.01.046 http://doi.org/10.1016/j.biomaterials.2012.01.046 .

Bishop, C. J.; Ketola, T M.; Tzeng, S. Y.; Sunshine, J. C.; Urttio, A.; Lemmetyinen, H., Vuorimaa-Laukkanen, E., Yliperttula, M.; Green, J. J . The effect and role of carbon atoms in poly(beta-amino ester)s for DNA Binding and Gene Delivery . J. Am. Chem. Soc. , 2013 . 135 6951 - 6957 . DOI: 10.1021/ja4002376 http://doi.org/10.1021/ja4002376 .

Chang, K. L.; Higuchi, Y.; Kawakami, S.; Yamashita, F.; Hashida, M . Development of lysine-histidine dendron modified chitosan for improving transfection efficiency in HEK293 cells . J. Control. Release , 2011 . 156 195 - 202 . DOI: 10.1016/j.jconrel.2011.07.021 http://doi.org/10.1016/j.jconrel.2011.07.021 .

Wen, Y.; Guo, Z.; Du, Z.; Fang, R.; Wu, H.; Zeng, X.; Wang, C.; Feng, M.; Pan, S . Serum tolerance and endosomal escape capacity of histidine-modified pDNA-loaded complexes based on polyamidoamine dendrimer derivatives . Biomaterials , 2012 . 33 8111 - 8121 . DOI: 10.1016/j.biomaterials.2012.07.032 http://doi.org/10.1016/j.biomaterials.2012.07.032 .

Liu, X.; Liu, C.; Zhou, J.; Chen, C.; Qu, F.; Rossi, J. J.; Rocchi, P.; Peng, L . Promoting siRNA delivery via enhanced cellular uptake using an arginine-decorated amphiphilic dendrimer . Nanoscale , 2015 . 7 3867 - 3875 . DOI: 10.1039/C4NR04759A http://doi.org/10.1039/C4NR04759A .

Kim, J. B.; Choi, J. S.; Nam, K.; Lee, M.; Park, J. S.; Lee, J. K . Enhanced transfection of primary cortical cultures using arginine-grafted PAMAM dendrimer, PAMAM-Arg . J. Control. Release , 2006 . 114 110 - 117 . DOI: 10.1016/j.jconrel.2006.05.011 http://doi.org/10.1016/j.jconrel.2006.05.011 .

Kim, T.; Bai, C. Z.; Nam, K.; Park, J . Comparison between arginine conjugated PAMAM dendrimers with structural diversity for gene delivery systems . J. Control. Release , 2009 . 136 132 - 139 . DOI: 10.1016/j.jconrel.2009.01.028 http://doi.org/10.1016/j.jconrel.2009.01.028 .

Liu, J . Pharmacology of oleanolic acid and ursolic acid . J. Ethnopharmacol , 1995 . 49 57 - 68 . DOI: 10.1016/0378-8741(95)90032-2 http://doi.org/10.1016/0378-8741(95)90032-2 .

Andersson, D.; Cheng, Y.; Duan, R. D . Ursolic acid inhibits the formation of aberrant crypt foci and affects colonic sphingomyelin hydrolyzing enzymes in azoxymethane-treated rats . J. Cancer Res. Clin. Oncol , 2008 . 134 101 - 107 . .

Furtado, R. A.; Rodrigues, É. P.; Araujo, F. R. R.; Oliveira, W. L.; Furtado, M. A.; Castro, M. B.; Cunha, W. R.; Tavares, D. C . Ursolic acid and oleanolic acid suppress preneoplastic lesions induced by 1,2-dimethylhydrazine in rat colon . Toxicol. Pathol. , 2008 . 36 576 - 580 . DOI: 10.1177/0192623308317423 http://doi.org/10.1177/0192623308317423 .

Gao, J . Hepatoprotective activity of terminalia catappa l. leaves and its two triterpenoids . J. Pharm. Pharmacol. , 2004 . 56 1449 - 1455 . DOI: 10.1211/0022357044733 http://doi.org/10.1211/0022357044733 .

Liu, J . The Effects of 10 triterpenoid compounds on experimental liver injury in mice . Fundam. Appl. Toxicol. , 1994 . 22 34 - 40 . DOI: 10.1006/faat.1994.1005 http://doi.org/10.1006/faat.1994.1005 .

Martin-Aragón, S.; de Las Heras, B.; Sanchez-Reus, M. I.; Benedi, J . Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damage in rats and primary cultures of rat hepatocytes . Exp. Toxicol. Pathol. , 2001 . 53 199 - 206 . DOI: 10.1078/0940-2993-00185 http://doi.org/10.1078/0940-2993-00185 .

Saravanan, R.; Viswanathan, P.; Pugalendi, K. V . Protective effect of ursolic acid on ethanol-mediated experimental liver damage in rats . Life Sci. , 2006 . 78 713 - 718 . DOI: 10.1016/j.lfs.2005.05.060 http://doi.org/10.1016/j.lfs.2005.05.060 .

Somova, L. O.; Nadar, A.; Rammanan, P.; Shode, F. O . Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental hypertension . Phytomedicine , 2003 . 10 115 - 121 . DOI: 10.1078/094471103321659807 http://doi.org/10.1078/094471103321659807 .

Ovesná, Z.; Kozics, K.; Slamenovˇ, D . Protective effects of ursolic acid and oleanolic acid in leukemic cells . Mutation Res , 2006 . 600 131 - 137 . DOI: 10.1016/j.mrfmmm.2006.03.008 http://doi.org/10.1016/j.mrfmmm.2006.03.008 .

Shishodia, S.; Majumdar, S.; Banerjee, S.; Aggarwal, B. B . Ursolic acid inhibits nuclear factor-kappaB activation induced by carcinogenic agents through suppression of IkappaBalpha kinase and p65 phosphorylation: correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1 . Cancer Res. , 2003 . 63 4375 - 83 . .

Moon H. K.; Yang, E. S.; Park, J. W . Protection of per-oxynitrite-induced DNA damage by dietary antioxidant . Arch. Pharm. Res. , 2006 . 29 213 - 217 . DOI: 10.1007/BF02969396 http://doi.org/10.1007/BF02969396 .

Lee, I.; Lee, J.; Lee, Y. H.; Leonard, J . Ursolic acid-induced changes in tumor growth, O2 consumption, and tumor interstitial fluid pressure . Anticancer Res. , 2001 . 21 2827 - 2833 . .

Yim, E. K.; Lee, M. J.; Lee, K. H., Um, S. J.; Park, J. S . Antiproliferative and antiviral mechanisms of ursolic acid and dexamethasone in cervical carcinoma cell lines . Int. J. Gynecol. Cancer. , 2006 . 16 2023 - 2031 . DOI: 10.1111/ijg.2006.16.issue-6 http://doi.org/10.1111/ijg.2006.16.issue-6 .

Huang, M. T.; Ho, C. T.; Wang, Z. Y.; Ferraro, T.; Lou, Y. R.; Stauber, K.; Ma, W.; Georgiadis, C.; Laskin, J. D.; Conney, A. K . Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid . Cancer. Res. , 1994 . 54 701 - 708 . .

Tokuda, H.; Ohigashi, H.; Koshimizu, K.; Ito, Y . Inhibitory effects of ursolic and oleanolic acid on skin tumor promotion by 12- O -tetradecanoylphorbol-13-acetate . Cancer Lett. , 1986 . 33 279 - 285 . DOI: 10.1016/0304-3835(86)90067-4 http://doi.org/10.1016/0304-3835(86)90067-4 .

Kim, K. A.; Lee, J. S.; Park, H. J.; Kim, J. W.; Kim, C. J.; Shim, I. S.; Kim, N. J.; Han, S. M.; Lim, S . Inhibition of cytochrome P450 activities by oleano-lic acid and ursolic acid in human liver microsomes . Life Sci. , 2004 . 74 2769 - 2779 . DOI: 10.1016/j.lfs.2003.10.020 http://doi.org/10.1016/j.lfs.2003.10.020 .

Ramos, A. A.; Lima, C. F.; Pereira, M. L.; Fernandes-Ferreira, M.; Pereira-Wilson, C . Antigenotoxic effects of quercetin, rutin and ursolic acid on HepG2 cells: evaluation by the comet assay . Toxicol. Lett. , 2008 . 177 66 - 73 . DOI: 10.1016/j.toxlet.2008.01.001 http://doi.org/10.1016/j.toxlet.2008.01.001 .

Chiang, L. C.; Chiang, W.; Chang, M. Y.; Ng, L. T.; Lin, C. C. . Antileukemic activity of selected natural products in Taiwan. . Am. J. Chin. Med. , 2003 . 31 37 - 46 . DOI: 10.1142/S0192415X03000825 http://doi.org/10.1142/S0192415X03000825 .

Fan, Y. M.; Xu, L. Z.; Gao, J.; Wang, Y.; Tang, X. H. Zhao, X. N.; Zhang, Z. X . Phytochemical and antiinflammatory studies on Terminalia catappa . Fitoterapia , 2004 . 75 253 - 260 . DOI: 10.1016/j.fitote.2003.11.007 http://doi.org/10.1016/j.fitote.2003.11.007 .

Peng, Q.; Zhu, J.; Yu, Y.; Hoffman, L.; Yang, X . Hyperbranched lysine-arginine copolymer for gene delivery . J. Biomater. Sci. Polym. Ed. , 2015 . 26 1163 - 1177 . DOI: 10.1080/09205063.2015.1080482 http://doi.org/10.1080/09205063.2015.1080482 .

Resende, F. A.; Mattos de Andrade Barcala, C. A.; da Silva Faria, M. C.; Kato, F. H.; Cunha, W. R.; Tavares, D. C . Antimutagenicity of ursolic acid and oleanolic acid against doxorubicin-induced clastogenesis in Balb/c mice . Life Sci. , 2006 . 79 1268 - 1273 . DOI: 10.1016/j.lfs.2006.03.038 http://doi.org/10.1016/j.lfs.2006.03.038 .

Lu, J.; Zheng, Y. L.; Wu, D. M.; Luo, L.; Sun, D. X.; Shan, Q . Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose . Biochem. Pharmacol. , 2007 . 74 1078 - 1090 . DOI: 10.1016/j.bcp.2007.07.007 http://doi.org/10.1016/j.bcp.2007.07.007 .

Saravanan, R. Pugalendi, V . Impact of ursolic acid on chronic ethanol-induced oxidative stress in the rat heart . Pharmacol. Rep. , 2006 . 58 41 - 47 . .

Wang, Y.; He, Z.; Deng, S . Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury . Drug Des., Devel. Ther. , 2016 . 10 1663 - 1674 . .

Senthil, S.; Chandramohan, G.; Pugalendi, K. V . Isomers (oleanolic and ursolic acids) differ in their protective effect against isoproterenol-induced myocardial ischemia in rats . Int. J. Cardiol. , 2007 . 119 131 - 133 . DOI: 10.1016/j.ijcard.2006.07.108 http://doi.org/10.1016/j.ijcard.2006.07.108 .

Radhiga, T.; Rajamanickam, C.; Senthil, S.; Pugalendi, K. V . Effect of ursolic acid on cardiac marker enzymes, lipid profile and macroscopic enzyme mapping assay in isoproterenol-induced myocardial ischemic rats . Food Chem. Toxicol. , 2012 . 50 3971 - 3977 . DOI: 10.1016/j.fct.2012.07.067 http://doi.org/10.1016/j.fct.2012.07.067 .

Aguirre-Crespo, F.; Vergara-Galicia, J.; Villalobos-Molina, R.; López-Guerrero, J. J.; Navarrete-Vázquez, G.; Estrada-Soto, S . Ursolic acid mediates the vasorelaxant activity of Lepechinia caulescens via NO release in isolated rat thoracic aorta . Life Sci. , 2006 . 79 1062 - 1068 . DOI: 10.1016/j.lfs.2006.03.006 http://doi.org/10.1016/j.lfs.2006.03.006 .

Martınez-Gonzalez, J.; Rodrıguez-Rodrıguez, R.; Gonzalez-Dıez, M.; Rodrıguez, C.; Herrera, M. D.; Ruiz-Gutierrez, V.; Badimon, L . Oleanolic acid induces prostacyclin release in human vascular smooth muscle cells through a cyclooxygenase-2-dependent mechanism . J. Nutr. , 2008 . 138 443 - 448 . DOI: 10.1093/jn/138.3.443 http://doi.org/10.1093/jn/138.3.443 .

Somova, L. I.; Shode, F. O.; Mipando, M . Cardiotonic and antidysrhythmic effects of oleanolic and ursolic acids, methyl maslinate and uvaol . Phytomedicine , 2004 . 11 121 - 129 . DOI: 10.1078/0944-7113-00329 http://doi.org/10.1078/0944-7113-00329 .

Ikeda, Y.; Murakami, A.; Ohigashi, H . Ursolic acid: an anti- and pro-inflammatory triterpenoid . Mol. Nutr. Food Res. , 2008 . 52 26 - 42 . DOI: 10.1002/(ISSN)1613-4133 http://doi.org/10.1002/(ISSN)1613-4133 .

Messner, B . Ursolic acid causes DNA damage, p53-mediated, mitochondria-and caspase-dependent human endothelial cell apoptosis, and accelerates atherosclerotic plaque formation in vivo . Atherosclerosis , 2011 . 219 402 - 408 . DOI: 10.1016/j.atherosclerosis.2011.05.025 http://doi.org/10.1016/j.atherosclerosis.2011.05.025 .

Liu, Y.; Oh, S. J.; Chang, K. H.; Kim, Y. G.; Lee, M. Y . Antiplatelet effect of AMP-activated protein kinase activator and its potentiation by the phosphodiesterase inhibitor dipyridamole . Biochem. Pharmacol. , 2013 . 86 914 - 925 . DOI: 10.1016/j.bcp.2013.07.009 http://doi.org/10.1016/j.bcp.2013.07.009 .

Kim, M.; Han, C. H.; Lee, M. Y . Enhancement of platelet aggregation by ursolic acid and oleanolic acid . Biomol. Ther , 2014 . 22 254 - 259 . DOI: 10.4062/biomolther.2014.008 http://doi.org/10.4062/biomolther.2014.008 .

Liu, J . Oleanolic acid and ursolic acid: research perspectives . J. Ethnopharmacol. , 2005 . 100 92 - 94 . DOI: 10.1016/j.jep.2005.05.024 http://doi.org/10.1016/j.jep.2005.05.024 .

Nahak, P.; Karmakar, G.; Chettri, P.; Roy, B.; Guha, P.; Besra, S. E.; Soren, A.; Bykov, A. G.; Akentiev, A. V.; Noskov, B. A.; Panda, A. K . Influence of lipid core material on physicochemical characteristics of an ursolic acid-loaded nanostructured lipid carrier: an attempt to enhance anticancer activity . Langmuir , 2016 . 32 9816 - 9825 . DOI: 10.1021/acs.langmuir.6b02402 http://doi.org/10.1021/acs.langmuir.6b02402 .

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. , 2017 . 25 ( 12 ): 1172 - 1186 . DOI: 10.1007/s13233-017-5160-3 http://doi.org/10.1007/s13233-017-5160-3 .

Bisio, A.; Romussi, G.; Russo, E.; Cafaggi, S.; Schito, A. M.; Repetto, B.; De Tommasi, N . Antimicrobial activity of the ornamental species salvia corrugata, a potential new crop for extractive purposes . J. Agric. Food Chem. , 2008 . 56 10468 - 10472 . DOI: 10.1021/jf802200x http://doi.org/10.1021/jf802200x .

Von Seel, F. in " Grundlagen der analytischen Chemie, Vol. 82”, ed. By Geier, G., Verlag Chemie, Weinheim, 1970, p. 962.

Aravindan, L.; Bicknell, K. A.; Brooks, G.; Khutoryanskiya, V. V.; Williams, A. C . Effect of acyl chain length on transfection efficiency and toxicity of polyethylenimine . Int. J. Pharm. , 2009 . 378 201 - 210 . DOI: 10.1016/j.ijpharm.2009.05.052 http://doi.org/10.1016/j.ijpharm.2009.05.052 .

Benns, J. M.; Choi, J. S.; Mahato, R. I.; Park, J. S.; Kim, S. W . pH-sensitive cationic polymer gene delivery vehicle: N -Ac-poly(L-histidine)-graft-poly(L-lysine) comb shaped polymer . Bioconj. Chem. , 2000 . 11 637 - 645 . DOI: 10.1021/bc0000177 http://doi.org/10.1021/bc0000177 .

Fernandez, L . Solubilization and release properties of dendrimers evaluation as prospective drug delivery systems . J. Supramol. Chem. , 2006 . 18 633 - 643 . DOI: 10.1080/10610270601012776 http://doi.org/10.1080/10610270601012776 .

Santo, M.; Fox, M. A . Hydrogen bonding interactions between Starburst dendrimers and several molecules of biological interest . Phys. Org. Chem. , 1999 . 12 293 - 307 . DOI: 10.1002/(ISSN)1099-1395 http://doi.org/10.1002/(ISSN)1099-1395 .

Cheng, Y.; Xu, Z.; Ma, M.; Xu, T . Dendrimers as drug carriers: applications in different routes of drug administration . J. Pharm. Sci. , 2008 . 97 123 - 143 . DOI: 10.1002/jps.21079 http://doi.org/10.1002/jps.21079 .

Milhem, O. M.; Myles, C.; McKeown, N. B.; Attwood, D.; D’Emanuele, A . Polyamidoamine Starburst dendrimers as solubility enhancers . Int. J. Pharm. , 2000 . 197 239 - 241 . DOI: 10.1016/S0378-5173(99)00463-9 http://doi.org/10.1016/S0378-5173(99)00463-9 .

Kolhe, P.; Misra, E.; Kannan, R. M.; Kannan, S.; Lieh-Lai, M . Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers . Int. J. Pharm. , 2003 . 259 143 - 160 . DOI: 10.1016/S0378-5173(03)00225-4 http://doi.org/10.1016/S0378-5173(03)00225-4 .

Twyman, L. J.; Beezer, A. E.; Esfand, R.; Hardy, M. J.; Mitchell, J. C . The synthesis of water soluble dendrimers, and their application as possible drug delivery systems . Tetrahedron Lett. , 1999 . 40 1743 - 1746 . DOI: 10.1016/S0040-4039(98)02680-X http://doi.org/10.1016/S0040-4039(98)02680-X .

Alfei, S.; Castellaro, S.; Taptue, G. B . Synthesis and NMR characterization of dendrimers based on 2, 2-bis-(hydroxymethyl)-propanoic acid (bis-HMPA) containing peripheral amino acid residues for gene transfection . Org. Commun. , 2017 . 10 144 - 177 . DOI: 10.25135/acg.oc. http://doi.org/10.25135/acg.oc. .

Seebacher, W.; Simic, N.; Weis, R.; Saf, R.; Kunert, O . Spectral assignments and reference data . Magn. Reson. Chem. , 2003 . 41 636 - 638 . DOI: 10.1002/(ISSN)1097-458X http://doi.org/10.1002/(ISSN)1097-458X .

Eichman, J. D.; Bielinska, A. S. U.; Kukowska-Latallo, J. F.; Baker J. R. Jr . The use of PA-MAM dendrimers in the efficient transfer of genetic material into cells . Sci. Technol. Today , 2000 . 3 232 - 245 . DOI: 10.1016/S1461-5347(00)00273-X http://doi.org/10.1016/S1461-5347(00)00273-X .

Wang, J. Q.; Mao, W. W.; Lock, L. L.; Tang, J. B.; Sui, M. H.; Sun, W. L.; Cui, H. G.; Xu, D.; Shen, Y. Q . The role of micelle size in tumor accumulation, penetration, and treatment . ACS Nano , 2015 . 9 7195 - 7206 . DOI: 10.1021/acsnano.5b02017 http://doi.org/10.1021/acsnano.5b02017 .

Yu, H.; Cui, Z.; Yu, P.; Guo, C.; Feng, B.; Jiang, T.; Wang, S.; Yin, Q.; Zhong, D.; Yang, X.; Zhang, Z.; Li, Y . pH- and NIR light-responsive micelles with hyperthermia-triggered tumor penetration and cytoplasm drug release to reverse doxorubicin resistance in breast cancer . Adv. Funct. Mater. , 2015 . 25 2489 - 2500 . DOI: 10.1002/adfm.201404484 http://doi.org/10.1002/adfm.201404484 .

浏览量

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

2026-9 Contents

Pyrimidoisoindigo-based Polymers for Ambipolar Charge Transport

One-handed Helical Poly(m-terphenyl acetylene)s with Broad Optical Activity Range from Ultraviolet-Visible to Near-infrared Regions

A Paradigm for BF3 Co-initiated Cationic Polymerization with Low Dispersity: Introducing Acetonitrile and Lowering the Reaction Temperature

Topology-regulated Co-assembly of Single Chain Polymer Nanoparticles and Block Copolymers into Hierarchical Micelle@Vesicle Composite Structures