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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Antitumor Activity of Cyclodextrin-based Supramolecular Platinum Prodrug In vitro and In vivo

Author(s): Yu-Hui Zhang, Jie Wang, Siqintana Xin, Li-Juan Wang and Xianliang Sheng*

Volume 16, Issue 11, 2019

Page: [1296 - 1301] Pages: 6

DOI: 10.2174/1570180816666190618114505

Abstract

Background: Considering the limitations of cisplatin in clinical application, there is ongoing research to fabricate new platinum-containing prodrug which are highly effective to tumor cells and have low toxicity to normal cells.

Methods: In this study, a cyclodextrin-based supramolecular platinum prodrug that is 6,6’-ophenylenediseleno- bridged bis (β-cyclodextrin)s (CD) and its potassium tetrachloroplatinate(II) complex was reported. The cytotoxicity experiments were performed to evaluate the anticancer activities of supramolecular prodrug in vitro by means of MTT assay. The practical application of supramolecular prodrug in tumor treatment in vivo were evaluated using BALB/c nude mice model bearing Hela cancer cells.

Results: Compared with commercial anticancer drug cisplatin, the resultant cyclodextrin-based platinum prodrug exhibited comparative anticancer effect but with much lower toxicity side effects in vitro and in vivo.

Conclusion: The cyclodextrin-based supramolecular platinum prodrug displayed antitumor activity comparable to the commercial antitumor drug cisplatin but with lower side effects both in vitro and in vivo, implying that the two adjacent cyclodextrin cavities not merely act as desired solubilizer, but also endowed the prodrug with cell permeability through the interaction of cyclodextrin with phospholipids and cholesterol on cell membrane.

Keywords: β-cyclodextrin, prodrug, water solubility, chemotherapy, cisplatin, supramolecular chemistry.

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[1]
Wang, D.; Lippard, S.J. Cellular processing of platinum anticancer drugs. Nat. Rev. Drug Discov., 2005, 4(4), 307-320.
[http://dx.doi.org/10.1038/nrd1691] [PMID: 15789122]
[2]
Xue, X.; You, S.; Zhang, Q.; Wu, Y.; Zou, G.Z.; Wang, P.C.; Zhao, Y-L.; Xu, Y.; Jia, L.; Zhang, X.; Liang, X-J. Mitaplatin increases sensitivity of tumor cells to cisplatin by inducing mitochondrial dysfunction. Mol. Pharm., 2012, 9(3), 634-644.
[http://dx.doi.org/10.1021/mp200571k] [PMID: 22289032]
[3]
Wang, X.; Wang, X.; Guo, Z. Functionalization of platinum complexes for biomedical applications. Acc. Chem. Res., 2015, 48(9), 2622-2631.
[http://dx.doi.org/10.1021/acs.accounts.5b00203] [PMID: 26247558]
[4]
Kelland, L. The resurgence of platinum-based cancer chemotherapy. Nat. Rev. Cancer, 2007, 7(8), 573-584.
[http://dx.doi.org/10.1038/nrc2167] [PMID: 17625587]
[5]
Yang, H.; Kong, W.; He, L.; Zhao, J-J.; O’Donnell, J.D.; Wang, J.; Wenham, R.M.; Coppola, D.; Kruk, P.A.; Nicosia, S.V.; Cheng, J.Q. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res., 2008, 68(2), 425-433.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2488] [PMID: 18199536]
[6]
Dasari, S.; Tchounwou, P.B. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur. J. Pharmacol., 2014, 740, 364-378.
[http://dx.doi.org/10.1016/j.ejphar.2014.07.025] [PMID: 25058905]
[7]
Kishimoto, S.; Yasuda, M.; Suzuki, R.; Fukushima, S. Intracellular uptake of an antitumor-active azole-bridged dinuclear platinum(II) complex in cisplatin-resistant tumor cells. Biometals, 2016, 29(6), 1075-1083.
[http://dx.doi.org/10.1007/s10534-016-9978-5] [PMID: 27787693]
[8]
Khiati, S.; Luvino, D.; Oumzil, K.; Chauffert, B.; Camplo, M.; Barthélémy, P. Nucleoside-lipid-based nanoparticles for cisplatin delivery. ACS Nano, 2011, 5(11), 8649-8655.
[http://dx.doi.org/10.1021/nn202291k] [PMID: 21961944]
[9]
Min, Y.; Mao, C-Q.; Chen, S.; Ma, G.; Wang, J.; Liu, Y. Combating the drug resistance of cisplatin using a platinum prodrug based delivery system. Angew. Chem. Int. Ed. Engl., 2012, 51(27), 6742-6747.
[http://dx.doi.org/10.1002/anie.201201562] [PMID: 22639083]
[10]
Xue, X.; Hall, M.D.; Zhang, Q.; Wang, P.C.; Gottesman, M.M.; Liang, X-J. Nanoscale drug delivery platforms overcome platinum-based resistance in cancer cells due to abnormal membrane protein trafficking. ACS Nano, 2013, 7(12), 10452-10464.
[http://dx.doi.org/10.1021/nn405004f] [PMID: 24219825]
[11]
Yang, Y.; Zhang, Y-M.; Chen, Y.; Chen, J-T.; Liu, Y. Targeted polysaccharide nanoparticle for adamplatin prodrug delivery. J. Med. Chem., 2013, 56(23), 9725-9736.
[http://dx.doi.org/10.1021/jm4014168] [PMID: 24252070]
[12]
Chin, C.F.; Tian, Q.; Setyawati, M.I.; Fang, W.; Tan, E.S.Q.; Leong, D.T.; Ang, W.H. Tuning the activity of platinum(IV) anticancer complexes through asymmetric acylation. J. Med. Chem., 2012, 55(17), 7571-7582.
[http://dx.doi.org/10.1021/jm300580y] [PMID: 22876932]
[13]
Fang, T.; Ye, Z.; Wu, J.; Wang, H. Reprogramming axial ligands facilitates the self-assembly of a platinum(iv) prodrug: Overcoming drug resistance and safer in vivo delivery of cisplatin. Chem. Commun. (Camb.), 2018, 54(66), 9167-9170.
[http://dx.doi.org/10.1039/C8CC03763A] [PMID: 30062328]
[14]
Yu, G.; Zhang, M.; Saha, M.L.; Mao, Z.; Chen, J.; Yao, Y.; Zhou, Z.; Liu, Y.; Gao, C.; Huang, F.; Chen, X.; Stang, P.J. Antitumor activity of a unique polymer that incorporates a fluorescent self-assembled metallacycle. J. Am. Chem. Soc., 2017, 139(44), 15940-15949.
[http://dx.doi.org/10.1021/jacs.7b09224] [PMID: 29019660]
[15]
Skander, M.; Retailleau, P.; Bourrié, B.; Schio, L.; Mailliet, P.; Marinetti, A. N-heterocyclic carbene-amine Pt(II) complexes, a new chemical space for the development of platinum-based anticancer drugs. J. Med. Chem., 2010, 53(5), 2146-2154.
[http://dx.doi.org/10.1021/jm901693m] [PMID: 20148592]
[16]
Zhang, W.; Shen, J.; Su, H.; Mu, G.; Sun, J-H.; Tan, C-P.; Liang, X-J.; Ji, L-N.; Mao, Z-W. Co-delivery of cisplatin prodrug and chlorin e6 by mesoporous silica nanoparticles for chemo-photodynamic combination therapy to combat drug resistance. ACS Appl. Mater. Interfaces, 2016, 8(21), 13332-13340.
[http://dx.doi.org/10.1021/acsami.6b03881] [PMID: 27164222]
[17]
Chen, Y.; Huang, Z.; Zhao, H.; Xu, J-F.; Sun, Z.; Zhang, X. Supramolecular chemotherapy: Cooperative enhancement of antitumor activity by combining controlled release of oxaliplatin and consuming of spermine by Cucurbit[7]uril. ACS Appl. Mater. Interfaces, 2017, 9(10), 8602-8608.
[http://dx.doi.org/10.1021/acsami.7b01157] [PMID: 28194936]
[18]
Johnstone, T.C.; Suntharalingam, K.; Lippard, S.J. The next generation of platinum drugs: Targeted Pt (II) agents, nanoparticle delivery, and Pt (IV) prodrugs. Chem. Rev., 2016, 116(5), 3436-3486.
[http://dx.doi.org/10.1021/acs.chemrev.5b00597] [PMID: 26865551]
[19]
Yao, X.; Xie, C.; Chen, W.; Yang, C.; Wu, W.; Jiang, X. Platinum-incorporating poly(N-vinylpyrrolidone)-poly(aspartic acid) pseudoblock copolymer nanoparticles for drug delivery. Biomacromolecules, 2015, 16(7), 2059-2071.
[http://dx.doi.org/10.1021/acs.biomac.5b00479] [PMID: 26023705]
[20]
Kim, J.; Pramanick, S.; Lee, D.; Park, H.; Kim, W.J. Polymeric biomaterials for the delivery of platinum-based anticancer drugs. Biomater. Sci., 2015, 3(7), 1002-1017.
[http://dx.doi.org/10.1039/C5BM00039D] [PMID: 26221935]
[21]
Chen, Y.; Liu, Y. Cyclodextrin-based bioactive supramolecular assemblies. Chem. Soc. Rev., 2010, 39(2), 495-505.
[http://dx.doi.org/10.1039/B816354P] [PMID: 20111774]
[22]
Ma, X.; Zhao, Y. Biomedical applications of supramolecular systems based on host–guest interactions. Chem. Rev., 2015, 115(15), 7794-7839.
[http://dx.doi.org/10.1021/cr500392w] [PMID: 25415447]
[23]
Qu, D-H.; Wang, Q-C.; Zhang, Q-W.; Ma, X.; Tian, H. Photoresponsive host–guest functional systems. Chem. Rev., 2015, 115(15), 7543-7588.
[http://dx.doi.org/10.1021/cr5006342] [PMID: 25697681]
[24]
Zhang, Y-H.; Chen, Y.; Zhang, Y-M.; Yang, Y.; Chen, J-T.; Liu, Y. Recycling gene carrier with high efficiency and low toxicity mediated by L-cystine-bridged bis(β-cyclodextrin)s. Sci. Rep., 2014, 4, 7471.
[http://dx.doi.org/10.1038/srep07471] [PMID: 25503268]
[25]
Irie, T.; Uekama, K. Cyclodextrins in peptide and protein delivery. Adv. Drug Deliv. Rev., 1999, 36(1), 101-123.
[http://dx.doi.org/10.1016/S0169-409X(98)00057-X] [PMID: 10837711]
[26]
Zhang, Y-H.; Zhang, Y-M.; Chen, Y.; Yang, Y.; Liu, Y. Phenanthroline bridged bis (β-cyclodextrin)s/adamantane-carboxylic acid supramolecular complex as an efficient fluorescence sensor to Zn2+. Org. Chem. Front., 2014, 1, 355-360.
[http://dx.doi.org/10.1039/c3qo00054k]
[27]
Davis, M.E.; Brewster, M.E. Cyclodextrin-based pharmaceutics: past, present and future. Nat. Rev. Drug Discov., 2004, 3(12), 1023-1035.
[http://dx.doi.org/10.1038/nrd1576] [PMID: 15573101]
[28]
Song, N.; Yang, Y-W. Molecular and supramolecular switches on mesoporous silica nanoparticles. Chem. Soc. Rev., 2015, 44(11), 3474-3504.
[http://dx.doi.org/10.1039/C5CS00243E] [PMID: 25904466]
[29]
Zhang, Y-H.; Zhang, Y-M.; Yang, Y.; Chen, L-X.; Liu, Y. Controlled DNA condensation and targeted cellular imaging by ligand exchange in a polysaccharide-quantum dot conjugate. Chem. Commun. (Camb.), 2016, 52(36), 6087-6090.
[http://dx.doi.org/10.1039/C6CC01571A] [PMID: 27064053]
[30]
Zhang, Y-H.; Zhang, Y-M.; Zhao, Q-H.; Liu, Y. Simultaneous expression and transportation of insulin by supramolecular polysaccharide nanocluster. Sci. Rep., 2016, 6, 22654.
[http://dx.doi.org/10.1038/srep22654] [PMID: 26948978]
[31]
Liu, Y.; Wang, H.; Liang, P.; Zhang, H-Y. Water-soluble supramolecular fullerene assembly mediated by metallobridged β-cyclodextrins. Angew. Chem. Int. Ed. Engl., 2004, 43(20), 2690-2694.
[http://dx.doi.org/10.1002/anie.200352973] [PMID: 18629992]
[32]
Yang, Y.; Zhang, Y-M.; Chen, Y.; Zhao, D.; Chen, J-T.; Liu, Y. Construction of a graphene oxide based noncovalent multiple nanosupramolecular assembly as a scaffold for drug delivery. Chemistry, 2012, 18(14), 4208-4215.
[http://dx.doi.org/10.1002/chem.201103445] [PMID: 22374621]
[33]
Alley, M.C.; Scudiero, D.A.; Monks, A.; Hursey, M.L.; Czerwinski, M.J.; Fine, D.L.; Abbott, B.J.; Mayo, J.G.; Shoemaker, R.H.; Boyd, M.R. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res., 1988, 48(3), 589-601.
[PMID: 3335022]
[34]
Zeng, L.; Li, Y.; Li, T.; Cao, W.; Yi, Y.; Geng, W.; Sun, Z.; Xu, H. Selenium-platinum coordination compounds as novel anticancer drugs: selectively killing cancer cells via a reactive oxygen species (ROS)-mediated apoptosis route. Chem. Asian J., 2014, 9(8), 2295-2302.
[http://dx.doi.org/10.1002/asia.201402256] [PMID: 24844800]
[35]
Li, T.; Smet, M.; Dehaen, W.; Xu, H.; Chen, Y.; Cheng, L.; Liu, Z.; Xu, H. Selenium–platinum coordination dendrimers with controlled anti-cancer activity. ACS Appl. Mater. Interfaces, 2016, 8(6), 3609-3614.
[http://dx.doi.org/10.1021/acsami.5b07877] [PMID: 26390019]
[36]
Udo, K.; Hokonohara, K.; Motoyama, K.; Arima, H.; Hirayama, F.; Uekama, K. 5-Fluorouracil acetic acid/β-cyclodextrin conjugates: drug release behavior in enzymatic and rat cecal media. Int. J. Pharm., 2010, 388(1-2), 95-100.
[http://dx.doi.org/10.1016/j.ijpharm.2009.12.039] [PMID: 20036722]

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