Paclitaxel-tyroserleutide Conjugates Self-assembly into Nanocarrier for Drug Delivery

Author(s): Yongjia Liu, Leilei Shi, Bangshang Zhu*, Yue Su, Hui Li*, Xinyuan Zhu

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 8 , 2019

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Graphical Abstract:


Background: The drug-drug self-assembly was considered as a simple and efficient approach to prepare high drug loading nano-drug carriers and present new opportunities for cancer therapeutics. The strategy of PTX amphiphiles preparation would be a possible way to solve the poor water solubility of PTX.

Methods: The PTX-YSL conjugate were synthesized and characterized. The PTX-YSL nanocarriers was prepared by a simple self-assembly method. In vitro cell studies and pharmacokinetic studies were evaluated for their in vitro anti-tumor activities and blood retention time.

Results: The structures of PTX-YSL conjugate were confirmed by LC-MS, 1H NMR and FTIR. The size and morphology of the PTX-YSL self-assembled nanocarriers were observed with TEM and DLS. PTX-YSL nanocarriers could facilitate cellular uptake and had low cytotoxicity. PTX-YSL nanocarriers have longer blood retention for enhancing accumulation in the tumor tissues via EPR effect.

Conclusion: This drug delivery system formed by PTX-YSL conjugates constitutes a promising and effective drug carrier in cancer therapy.

Keywords: Paclitaxel, tyroserleutide, self-assembly, nanocarriers, drug delivery, circular dichroism.

Gupte, M.; Tuck, A.N.; Sharma, V.P.; Williams, K.J. Major differences between tumor and normal human cell fates after exposure to chemotherapeutic monofunctional alkylator. PLoS One, 2013, 8(9), e74071.
Hucke, A.; Ciarimboli, G. The role of transporters in the toxicity of chemotherapeutic drugs: Focus on transporters for organic cations. J. Clin. Pharmacol., 2016, 56(S7), S157-S172.
Markman, J.L.; Rekechenetskiy, A.; Holler, E.; Ljubimova, J.Y. Nanomedicine therapeutic approaches to overcome cancer drug resistance. Adv. Drug Deliv. Rev., 2013, 65(13), 1866-1879.
Joralemon, M.J.; McRae, S.; Emrick, T. PEGylated polymers for medicine: From conjugation to self-assembled systems. Chem. Commun. , 2010, 46(9), 1377-1393.
Yan, L.; Chen, W.; Zhu, X.; Huang, L.; Wang, Z.; Zhu, G.; Roy, V.A.L.; Yu, K.N.; Chen, X. Folic acid conjugated self-assembled layered double hydroxide nanoparticles for high-efficacy-targeted drug delivery. Chem. Commun. , 2013, 49(93), 10938-10940.
Kobayashi, H.; Turkbey, B.; Watanabe, R.; Choyke, P.L. Cancer drug delivery: Considerations in the rational design of nanosized bioconjugates. Bioconjug. Chem., 2014, 25, 2093-2100.
Farokhzad, O.C.; Langer, R. Impact of nanotechnology on drug delivery. ACS Nano, 2009, 3(1), 16-20.
Greish, K.; Nehoff, H.; Parayath, N.; Domanovitch, L.; Taurin, S. Nanomedicine for drug targeting: Strategies beyond the enhanced permeability and retention effect. Int. J. Nanomedicine, 2014, 9, 2539-2555.
Tammam, S.N.; Azzazy, H.M.E.; Lamprecht, A. How successful is nuclear targeting by nanocarriers? J. Control. Release, 2016, 229, 140-153.
Salatin, S.; Maleki-Dizaj, S.; Yari, K. An effect of the surface modification size and shape on cellular uptake of nanoparticles. Cell Biol. Int., 2015, 39, 881-890.
Gao, W.; Fang, R.; Thamphiwatana, S.; Luk, B.; Li, J.; Angsantikul, P.; Zhang, Q.; Hu, Z. Zhang. L. Modulating antibacterial immunity via bacterial membrane-coated nanoparticles. Nano Lett., 2015, 15(2), 1403-1409.
Hu, T.; Yang, J.; Cui, K.; Rao, Q.; Yin, T.; Tan, L.; Zhang, Y.; Li, Z.; Wang, G. Controlled slow-release drug-eluting stents for the prevention of coronary restenosis: Recent progress and future prospects. ACS Appl. Mater. Interfaces, 2015, 7(22), 11695-11712.
Jeong, K.; Kang, C.S.; Kim, Y.; Lee, Y.; Kwon, I.C.; Kim, S. Development of highly efficient nanocarrier-mediated delivery approaches for cancer therapy. Cancer Lett., 2016, 374(1), 31-43.
Hakeem, A.; Duan, R.; Zahid, F.; Dong, C.; Wang, B.; Hong, F.; Ou, X.W.; Jia, Y.M.; Lou, X.D.; Xia, F. Dual stimuli-responsive nano-vehicles for controlled drug delivery: mesoporous silica nanoparticles end-capped with natural chitosan. Chem. Commun. , 2014, 50(87), 13258-13271.
Ariga, K.; Hill, J.P.; Lee, M.V.; Vinu, A.; Charvet, R.; Acharya, S. Challenges and breakthroughs in recent research on self-assembly. Sci. Technol. Adv. Mater., 2008, 9(1), 014109.
Yan, N.; Sheng, Y.; Liu, H.; Zhu, Y.; Jiang, W. Templated self-assembly of block copolymers and morphology transformation driven by the rayleigh instability. Langmuir, 2015, 31(15), 1660-1669.
Lv, K.; Zhang, L.; Liu, M. Self-assembly of triangular amphiphiles into diverse nano/microstructures and release behavior of the hollow sphere. Langmuir, 2014, 30(31), 9295-9302.
Lepeltier, E.; Bourgaux, C.; Maksimenko, A.; Meneau, F.; Rosilio, V.; Sliwinski, E.; Zouhiri, F.; Desmaële, D.; Couvreur, P. Self-assembly of polyisoprenoyl gemcitabine conjugates: Influence of supramolecular organization on their biological activity. Langmuir, 2014, 30(22), 6348-6357.
Fumagalli, G.; Marucci, C.; Christodoulou, M.S.; Stella, B.; Dosio, F.; Passarella, D. Self-assembly drug conjugates for anticancer treatment. Drug Discov. Today, 2016, 21(8), 1321-1329.
Huang, P.; Wang, D.; Su, Y.; Huang, W.; Zhou, Y.; Cui, D.; Zhu, X.; Yan, D. Combination of small molecule prodrug and nanodrug delivery: Amphiphilic drug-drug conjugate for cancer therapy. J. Am. Chem. Soc., 2014, 136(33), 11748-11756.
Cheetham, A.G.; Zhang, P.; Lin, Y.; Lock, L.L.; Cui, H. Supramolecular nanostructures formed by anticancer drug assembly. J. Am. Chem. Soc., 2013, 135(8), 2907-291.
Hamley, I.W.; Castelletto, V. Self-assembly of peptide bioconjugates: Selected recent research highlights. Bioconjug. Chem., 2016, 28(3), 731-739.
De Santis, E.; Ryadnov, M.G. Peptide self-assembly for nanomaterials: The old new kid on the block. Chem. Soc. Rev., 2015, 44(22), 8288-8300.
Sinha, R.; Kim, G.J.; Nie, S.; Shin, D.M. Nanotechnology in cancer therapeutics: Bioconjugated nanoparticles for drug delivery. Mol. Cancer Ther., 2006, 5(8), 1909-1917.
Yao, Z.; Lu, R.; Jia, J.; Zhao, P.; Yang, J.; Zheng, M.; Lu, J.; Jin, M.; Yang, H.; Gao, W. The effect of tripeptide tyroserleutide (YSL) on animal models of hepatocarcinoma. Peptides, 2006, 27(6), 1167-1172.
Lu, R.; Jia, J.; Bao, L.; Fu, Z.; Li, G.; Wang, S.; Wang, Z.; Jin, M.; Gao, W.; Yao, Z. Experimental study of the inhibition of human hepatocarcinoma Bel7402 cells by the tripeptide tyroserleutide(YSL). Cancer Chemother. Pharmacol., 2006, 57(2), 248-256.
Kaspar, A.A.; Reichert, J.M. Future directions for peptide therapeutics development. Drug Discov. Today, 2013, 18(17), 807-817.
Gagandeep, S.; Novikoff, P.M.; Ott, M.; Gupta, S. Paclitaxel shows cytotoxic activity in human hepatocellular carcinoma cell lines. Cancer Lett., 1999, 136(1), 109-118.
Fang, S.; Niu, Y.; Zhang, W.; Zhang, Y.; Yu, L.; Zhang, Y.; Li, X. Liposome-like nanocapsules of dual drug-tailed betaine for cancer therapy. Int. J. Pharm., 2015, 493(1), 460-465.
Cheetham, A.G.; Lin, Y.; Lin, R.; Cui, H.G. Molecular design and synthesis of self-assembling camptothecin drug amphiphiles. Acta Pharmacol. Sin., 2017, 38(6), 874-884.
Zentner, G.M.; Rathi, R.; Shih, C.; McRea, J.C.; Seo, M.H.; Oh, H.; Rhee, B.G.; Mestecky, J.; Moldoveanu, Z.; Morgan, M.; Weitman, S. Biodegradable block copolymers for delivery of proteins and water-insoluble drugs. J. Control. Release, 2001, 72(1-3), 203-215.
Zhang, J.A.; Anyarambhatla, G.; Ma, L.; Ugwu, S.; Xuan, T.; Sardone, T.; Ahmad, I. Development and characterization of a novel Cremophor® EL free liposome-based paclitaxel (LEP-ETU) formulation. Eur. J. Pharm. Biopharm., 2005, 59(1), 177-187.
Ganta, S.; Devalapally, H.; Shahiwala, A.; Amiji, M. A review of stimuli-responsive nanocarriers for drug and gene delivery. J. Control. Release, 2008, 126(3), 187-204.
Liu, G.F.; Zhang, D.; Feng, C.L. Control of three-dimensional cell adhesion by the chirality of nanofibers in hydrogels. Angew. Chem. Int. Ed., 2014, 53(30), 7789-7793.
Dou, X.Q.; Li, P.; Zhang, D.; Feng, C.L. RGD anchored C2-benzene based PEG-like hydrogels as scaffolds for two and three dimensional cell cultures. J. Mater. Chem. , 2013, 1(29), 3562-3568.

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Article Details

Year: 2019
Page: [882 - 891]
Pages: 10
DOI: 10.2174/1570180815666180803124625
Price: $65

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