Improved Therapeutic Efficacy of Topotecan Against A549 Lung Cancer Cells with Folate-targeted Topotecan Liposomes

Author(s): Jingxin Zhang, Weiyue Shi, Gangqiang Xue, Qiang Ma, Haixin Cui, Liang Zhang*

Journal Name: Current Drug Metabolism

Volume 21 , Issue 11 , 2020


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Graphical Abstract:


Abstract:

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells.

Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models.

Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats.

Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time.

Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.

Keywords: Lung cancer, folate-targeted topotecan liposomes, sustained drug release, pharmacokinetics, antitumor efficiency, folate-specific targeting.

[1]
Detterbeck, F.C. Clinical presentation and evaluation of neuroendocrine tumors of the lung. Thorac. Surg. Clin., 2014, 24(3), 267-276.
[http://dx.doi.org/10.1016/j.thorsurg.2014.04.002] [PMID: 25065927]
[2]
Li, G.; He, L.; Zhang, E.; Shi, J.; Zhang, Q.; Le, A.D.; Zhou, K.; Tang, X. Overexpression of human papillomavirus (HPV) type 16 oncoproteins promotes angiogenesis via enhancing HIF-1α and VEGF expression in non-small cell lung cancer cells. Cancer Lett., 2011, 311(2), 160-170.
[http://dx.doi.org/10.1016/j.canlet.2011.07.012] [PMID: 21868151]
[3]
Li, X.; Feng, Y.; Liu, J.; Feng, X.; Zhou, K.; Tang, X. Epigallocatechin-3-gallate inhibits IGF-I-stimulated lung cancer angiogenesis through downregulation of HIF-1α and VEGF expression. J. Nutrigenet. Nutrigenomics, 2013, 6(3), 169-178.
[http://dx.doi.org/10.1159/000354402] [PMID: 24008975]
[4]
Hörmann, V.; Kumi-Diaka, J.; Durity, M.; Rathinavelu, A. Anticancer activities of genistein-topotecan combination in prostate cancer cells. J. Cell. Mol. Med., 2012, 16(11), 2631-2636.
[http://dx.doi.org/10.1111/j.1582-4934.2012.01576.x] [PMID: 22452992]
[5]
Gantar, M.; Dhandayuthapani, S.; Rathinavelu, A. Phycocyanin induces apoptosis and enhances the effect of topotecan on prostate cell line LNCaP. J. Med. Food, 2012, 15(12), 1091-1095.
[http://dx.doi.org/10.1089/jmf.2012.0123] [PMID: 23134462]
[6]
Suzuki, H.; Hirashima, T.; Kobayashi, M.; Sasada, S.; Okamoto, N.; Uehara, N.; Matsuura, Y.; Tamiya, M.; Morishita, N.; Higashiguchi, M.; Tsumori, T.; Kawase, I. Effect of topotecan as second-line chemotherapy for small cell lung cancer patients with interstitial lung disease. J. Chemother., 2011, 23(6), 367-370.
[http://dx.doi.org/10.1179/joc.2011.23.6.367] [PMID: 22233823]
[7]
Ma, Y.; Yang, Q.; Wang, L.; Zhou, X.; Zhao, Y.; Deng, Y. Repeated injections of PEGylated liposomal topotecan induces accelerated blood clearance phenomenon in rats. Eur. J. Pharm. Sci., 2012, 45(5), 539-545.
[http://dx.doi.org/10.1016/j.ejps.2011.11.014] [PMID: 22155543]
[8]
Hosomi, Y.; Shibuya, M.; Niho, S.; Ichinose, Y.; Kiura, K.; Sakai, H.; Takeda, K.; Kudo, S.; Eguchi, K.; Matsui, K.; Masuda, N.; Ando, M.; Watanabe, K. Phase II study of topotecan with cisplatin in Japanese patients with small cell lung cancer. Anticancer Res., 2011, 31(10), 3449-3456.
[PMID: 21965760]
[9]
Kumar, S.; Mokhtari, R.B.; Sheikh, R.; Wu, B.; Zhang, L.; Xu, P.; Man, S.; Oliveira, I.D.; Yeger, H.; Kerbel, R.S.; Baruchel, S. Metronomic oral topotecan with pazopanib is an active antiangiogenic regimen in mouse models of aggressive pediatric solid tumor. Clin. Cancer Res., 2011, 17(17), 5656-5667.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-0078] [PMID: 21788355]
[10]
Hashimoto, Y.; Uehara, Y.; Abu Lila, A.S.; Ishida, T.; Kiwada, H. Activation of TLR9 by incorporated pDNA within PEG-coated lipoplex enhances anti-PEG IgM production. Gene Ther., 2014, 21(6), 593-598.
[http://dx.doi.org/10.1038/gt.2014.32] [PMID: 24694537]
[11]
Lu, S.W.; Zhang, X.M.; Luo, H.M.; Fu, Y.C.; Xu, M.Y.; Tang, S.J. Clodronate liposomes reduce excessive scar formation in a mouse model of burn injury by reducing collagen deposition and TGF-β1 expression. Mol. Biol. Rep., 2014, 41(4), 2143-2149.
[http://dx.doi.org/10.1007/s11033-014-3063-3] [PMID: 24442318]
[12]
Paoli, E.E.; Ingham, E.S.; Zhang, H.; Mahakian, L.M.; Fite, B.Z.; Gagnon, M.K.; Tam, S.; Kheirolomoom, A.; Cardiff, R.D.; Ferrara, K.W. Accumulation, internalization and therapeutic efficacy of neuropilin-1-targeted liposomes. J. Control. Release, 2014, 178, 108-117.
[http://dx.doi.org/10.1016/j.jconrel.2014.01.005] [PMID: 24434424]
[13]
Yuba, E.; Tajima, N.; Yoshizaki, Y.; Harada, A.; Hayashi, H.; Kono, K. Dextran derivative-based pH-sensitive liposomes for cancer immunotherapy. Biomaterials, 2014, 35(9), 3091-3101.
[http://dx.doi.org/10.1016/j.biomaterials.2013.12.024] [PMID: 24406217]
[14]
Smith, D.E.; Hornstra, J.M.; Kok, R.M.; Blom, H.J.; Smulders, Y.M. Folic acid supplementation does not reduce intracellular homocysteine, and may disturb intracellular one-carbon metabolism. Clin. Chem. Lab. Med., 2013, 51(8), 1643-1650.
[http://dx.doi.org/10.1515/cclm-2012-0694] [PMID: 23740686]
[15]
Meisser-Redeuil, K.; Bénet, S.; Gimenez, C.; Campos-Giménez, E.; Maria, N. Determination of folate in infant formula and adult/pediatric nutritional formula by ultra-high performance liquid chromatography-tandem mass spectrometry: first Action 2013.13. J. AOAC Int., 2014, 97(4), 1121-1126.
[http://dx.doi.org/10.5740/jaoacint.14-055] [PMID: 25145147]
[16]
Ajuria-Morentin, I.; Mar-Medina, C.; Bereciartua-Urbieta, E.; Aguirre-Larracoechea, U.; Quintana-López, J.M.; Ruiz-Larrea, M.B. Determination of reference values for serum folate and vitamin B12 using three different immunoassays: is it worth making an effort to produce them in our laboratory? Clin. Lab., 2014, 60(7), 1135-1143.
[http://dx.doi.org/10.7754/Clin.Lab.2013.130729] [PMID: 25134382]
[17]
Zhang, L.; Zhang, Z.; Mason, R.P.; Sarkaria, J.N.; Zhao, D. Convertible MRI contrast: Sensing the delivery and release of anti-glioma nano-drugs. Sci. Rep., 2015, 5, 9874.
[http://dx.doi.org/10.1038/srep09874] [PMID: 25962872]
[18]
Zhang, L.; Yao, H.J.; Yu, Y.; Zhang, Y.; Li, R.J.; Ju, R.J.; Wang, X.X.; Sun, M.G.; Shi, J.F.; Lu, W.L. Mitochondrial targeting liposomes incorporating daunorubicin and quinacrine for treatment of relapsed breast cancer arising from cancer stem cells. Biomaterials, 2012, 33(2), 565-582.
[http://dx.doi.org/10.1016/j.biomaterials.2011.09.055] [PMID: 21983136]
[19]
Wang, X.X.; Li, Y.B.; Yao, H.J.; Ju, R.J.; Zhang, Y.; Li, R.J.; Yu, Y.; Zhang, L.; Lu, W.L. The use of mitochondrial targeting resveratrol liposomes modified with a dequalinium polyethylene glycol-distearoylphosphatidyl ethanolamine conjugate to induce apoptosis in resistant lung cancer cells. Biomaterials, 2011, 32(24), 5673-5687.
[http://dx.doi.org/10.1016/j.biomaterials.2011.04.029] [PMID: 21550109]
[20]
Lin, C.; Wong, B.C.K.; Chen, H.; Bian, Z.; Zhang, G.; Zhang, X.; Kashif Riaz, M.; Tyagi, D.; Lin, G.; Zhang, Y.; Wang, J.; Lu, A.; Yang, Z. Pulmonary delivery of triptolide-loaded liposomes decorated with anti-carbonic anhydrase IX antibody for lung cancer therapy. Sci. Rep., 2017, 7(1), 1097.
[http://dx.doi.org/10.1038/s41598-017-00957-4] [PMID: 28428618]
[21]
Xue, Y.; He, W. HongJuan, Y.; Yan, Z.; Wei, T.; Liang, Z.; RuiJun, J.; XiaoXing, W.; Yang, Y.; WanLiang, L. Pharmacokinetics and tissue distribution of dual-targeting daunorubicin liposomes in mice. Pharmacology, 2011, 87, 105-114.
[http://dx.doi.org/10.1159/000323222]
[22]
Yu, Y.; Wang, Z.H.; Zhang, L.; Yao, H.J.; Zhang, Y.; Li, R.J.; Ju, R.J.; Wang, X.X.; Zhou, J.; Li, N.; Lu, W.L. Mitochondrial targeting topotecan-loaded liposomes for treating drug-resistant breast cancer and inhibiting invasive metastases of melanoma. Biomaterials, 2012, 33(6), 1808-1820.
[http://dx.doi.org/10.1016/j.biomaterials.2011.10.085] [PMID: 22136714]
[23]
Marianecci, C.; Rinaldi, F.; Di Marzio, L.; Pozzi, D.; Caracciolo, G.; Manno, D.; Dini, L.; Paolino, D.; Celia, C.; Carafa, M. Interaction of pH-sensitive non-phospholipid liposomes with cellular mimetic membranes. Biomed. Microdevices, 2013, 15(2), 299-309.
[http://dx.doi.org/10.1007/s10544-012-9731-y] [PMID: 23239124]
[24]
Nie, Y.; Ji, L.; Ding, H.; Xie, L.; Li, L.; He, B.; Wu, Y.; Gu, Z. Cholesterol derivatives based charged liposomes for doxorubicin delivery: preparation, in vitro and in vivo characterization. Theranostics, 2012, 2(11), 1092-1103.
[http://dx.doi.org/10.7150/thno.4949] [PMID: 23227125]
[25]
Ho, E.A.; Osooly, M.; Strutt, D.; Masin, D.; Yang, Y.; Yan, H.; Bally, M. Characterization of long-circulating cationic nanoparticle formulations consisting of a two-stage PEGylation step for the delivery of siRNA in a breast cancer tumor model. J. Pharm. Sci., 2013, 102(1), 227-236.
[http://dx.doi.org/10.1002/jps.23351] [PMID: 23132529]
[26]
Leite, E.A.; Souza, C.M.; Carvalho-Júnior, A.D.; Coelho, L.G.; Lana, A.M.; Cassali, G.D.; Oliveira, M.C. Encapsulation of cisplatin in long-circulating and pH-sensitive liposomes improves its antitumor effect and reduces acute toxicity. Int. J. Nanomedicine, 2012, 7, 5259-5269.
[PMID: 23091378]
[27]
Zhang, Y.; Phung, T.; Dunlop, J.; Dalziel, J. hERG ion channel pharmacology: cell membrane liposomes in porous-supported lipid bilayers compared with whole-cell patch-clamping. Eur. Biophys. J., 2012, 41(11), 949-958.
[http://dx.doi.org/10.1007/s00249-012-0852-2] [PMID: 22936309]
[28]
Yoshino, K.; Nakamura, K.; Terajima, Y.; Kurita, A.; Matsuzaki, T.; Yamashita, K.; Isozaki, M.; Kasukawa, H. Comparative studies of irinotecan-loaded polyethylene glycol-modified liposomes prepared using different PEG-modification methods. Biochim. Biophys. Acta, 2012, 1818(11), 2901-2907.
[http://dx.doi.org/10.1016/j.bbamem.2012.07.011] [PMID: 22828450]
[29]
Liu, X.M.; Zhang, Y.; Chen, F.; Khutsishvili, I.; Fehringer, E.V.; Marky, L.A.; Bayles, K.W.; Wang, D. Prevention of orthopedic device-associated osteomyelitis using oxacillin-containing biomineral-binding liposomes. Pharm. Res., 2012, 29(11), 3169-3179.
[http://dx.doi.org/10.1007/s11095-012-0812-7] [PMID: 22733150]


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Article Details

VOLUME: 21
ISSUE: 11
Year: 2020
Published on: 20 August, 2020
Page: [902 - 909]
Pages: 8
DOI: 10.2174/1389200221999200820163337
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