Lapatinib-Loaded Nanocapsules Enhances Antitumoral Effect in Human Bladder Cancer Cell

Overview

Journal Front Oncol

Specialty Oncology

Date 2019 Apr 27

PMID 31024833

Citations 8

Authors

Julieti Huch Buss

Karine Rech Begnini

Franciele Aline Bruinsmann

Taise Ceolin

Mariana Souza Sonego

Adriana Raffin Pohlmann

Silvia Staniscuaski Guterres

Tiago Collares

Fabiana Kommling Seixas

Affiliations

Soon will be listed here.

Abstract

Transitional cell carcinoma (TCC) represents the most frequent type of bladder cancer. Recently, studies have focused on molecular tumor classifications in order to diagnose tumor subtypes and predict future clinical behavior. Increased expression of HER1 and HER2 receptors in TTC is related to advanced stage tumors. Lapatinib is an important alternative to treat tumors that presents this phenotype due to its ability to inhibit tyrosine kinase residues associated with HER1 and HER2 receptors. This study evaluated the cytotoxicity induced by LAP-loaded nanocapsules (NC-LAP) compared to LAP in HER-positive bladder cancer cell. The cytotoxicity induced by NC-LAP was evaluated through flow cytometry, clonogenic assay and RT-PCR. NC-LAP at 5 μM reduced the cell viability and was able to induce G0/G1 cell cycle arrest with up-regulation of p21. Moreover, NC-LAP treatment presented significantly higher apoptotic rates than untreated cells and cells incubated with drug-unloaded nanocapsules (NC) and an increase in Bax/Bcl-2 ratio was observed in T24 cell line. Furthermore, clonogenic assay demonstrated that NC-LAP treatment eliminated almost all cells with clonogenic capacity. In conclusion, NC-LAP demonstrate antitumoral effect in HER-positive bladder cells by inducing cell cycle arrest and apoptosis exhibiting better effects compared to the non-encapsulated lapatinib. Our work suggests that the LAP loaded in nanoformulations could be a promising approach to treat tumors that presents EGFR overexpression phenotype.

Citing Articles

Precision Nanomedicine: Lapatinib-Loaded Chitosan-Gold Nanoparticles Targeting LINC01615 for Lung Cancer Therapy.

Rezaei Aghdam H, Peymani M, Salehzadeh A, Rouhi L, Zarepour A, Zarrabi A AAPS J. 2024; 27(1):4.

PMID: 39562465 DOI: 10.1208/s12248-024-00990-y.

Nanotechnology in the development of small and large molecule tyrosine kinase inhibitors and immunotherapy for the treatment of HER2-positive breast cancer.

Ejigah V, Mandala B, Akala E J Cancer Metastasis Res. 2024; 4(2):6-22.

PMID: 38966076 PMC: 11223443.

Formulation of Lipid-Based Nanoparticles for Simultaneous Delivery of Lapatinib and Anti-Survivin siRNA for HER2+ Breast Cancer Treatment.

Eljack S, David S, Chourpa I, Faggad A, Allard-Vannier E Pharmaceuticals (Basel). 2022; 15(12).

PMID: 36558904 PMC: 9784347. DOI: 10.3390/ph15121452.

Polymeric nanoparticles targeting Sialyl-Tn in gastric cancer: A live tracking under flow conditions.

Diniz F, Azevedo M, Sousa F, Osorio H, Campos D, Sampaio P Mater Today Bio. 2022; 16:100417.

PMID: 36105678 PMC: 9465339. DOI: 10.1016/j.mtbio.2022.100417.

Targeted elastin-like polypeptide fusion protein for near-infrared imaging of human and canine urothelial carcinoma.

Aayush A, Darji S, Dhawan D, Enstrom A, Broman M, Idrees M Oncotarget. 2022; 13:1004-1016.

PMID: 36082359 PMC: 9447490. DOI: 10.18632/oncotarget.28271.

References

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

Sridhar S, Seymour L, Shepherd F . Inhibitors of epidermal-growth-factor receptors: a review of clinical research with a focus on non-small-cell lung cancer. Lancet Oncol. 2003; 4(7):397-406. DOI: 10.1016/s1470-2045(03)01137-9. View

Allen T, Cullis P . Drug delivery systems: entering the mainstream. Science. 2004; 303(5665):1818-22. DOI: 10.1126/science.1095833. View

Bennasroune A, Gardin A, Aunis D, Cremel G, Hubert P . Tyrosine kinase receptors as attractive targets of cancer therapy. Crit Rev Oncol Hematol. 2004; 50(1):23-38. DOI: 10.1016/j.critrevonc.2003.08.004. View

Kabanov A, Batrakova E, Sriadibhatla S, Yang Z, Kelly D, Alakov V . Polymer genomics: shifting the gene and drug delivery paradigms. J Control Release. 2004; 101(1-3):259-71. DOI: 10.1016/j.jconrel.2004.07.009. View

Tibes R, Trent J, Kurzrock R . Tyrosine kinase inhibitors and the dawn of molecular cancer therapeutics. Annu Rev Pharmacol Toxicol. 2005; 45:357-84. DOI: 10.1146/annurev.pharmtox.45.120403.100124. View

Rotterud R, Nesland J, Berner A, Fossa S . Expression of the epidermal growth factor receptor family in normal and malignant urothelium. BJU Int. 2005; 95(9):1344-50. DOI: 10.1111/j.1464-410X.2005.05497.x. View

Burris 3rd H, Hurwitz H, Dees E, Dowlati A, Blackwell K, ONeil B . Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas. J Clin Oncol. 2005; 23(23):5305-13. DOI: 10.1200/JCO.2005.16.584. View

Nelson M, Dolder C . Lapatinib: a novel dual tyrosine kinase inhibitor with activity in solid tumors. Ann Pharmacother. 2006; 40(2):261-9. DOI: 10.1345/aph.1G387. View

10.

Memon A, Sorensen B, Meldgaard P, Fokdal L, Thykjaer T, Nexo E . The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4: a study in bladder cancer patients. Br J Cancer. 2006; 94(11):1703-9. PMC: 2361308. DOI: 10.1038/sj.bjc.6603154. View

11.

Kabanov A . Polymer genomics: an insight into pharmacology and toxicology of nanomedicines. Adv Drug Deliv Rev. 2006; 58(15):1597-621. PMC: 1853357. DOI: 10.1016/j.addr.2006.09.019. View

12.

Kramer C, Klasmeyer K, Bojar H, Schulz W, Ackermann R, Grimm M . Heparin-binding epidermal growth factor-like growth factor isoforms and epidermal growth factor receptor/ErbB1 expression in bladder cancer and their relation to clinical outcome. Cancer. 2007; 109(10):2016-24. DOI: 10.1002/cncr.22627. View

13.

Franken N, Rodermond H, Stap J, Haveman J, van Bree C . Clonogenic assay of cells in vitro. Nat Protoc. 2007; 1(5):2315-9. DOI: 10.1038/nprot.2006.339. View

14.

Mukherjee A, Dhadda A, Shehata M, Chan S . Lapatinib: a tyrosine kinase inhibitor with a clinical role in breast cancer. Expert Opin Pharmacother. 2007; 8(13):2189-204. DOI: 10.1517/14656566.8.13.2189. View

15.

Kassouf W, Black P, Tuziak T, Bondaruk J, Lee S, Brown G . Distinctive expression pattern of ErbB family receptors signifies an aggressive variant of bladder cancer. J Urol. 2007; 179(1):353-8. PMC: 2680144. DOI: 10.1016/j.juro.2007.08.087. View

16.

Youle R, Strasser A . The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2007; 9(1):47-59. DOI: 10.1038/nrm2308. View

17.

Warheit D . How meaningful are the results of nanotoxicity studies in the absence of adequate material characterization?. Toxicol Sci. 2008; 101(2):183-5. DOI: 10.1093/toxsci/kfm279. View

18.

Batrakova E, Kabanov A . Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. J Control Release. 2008; 130(2):98-106. PMC: 2678942. DOI: 10.1016/j.jconrel.2008.04.013. View

19.

McHugh L, Sayan A, Mejlvang J, Leyshon Griffiths T, Sun Y, Manson M . Lapatinib, a dual inhibitor of ErbB-1/-2 receptors, enhances effects of combination chemotherapy in bladder cancer cells. Int J Oncol. 2009; 34(4):1155-63. DOI: 10.3892/ijo_00000244. View

20.

Johnson L . Protein kinase inhibitors: contributions from structure to clinical compounds. Q Rev Biophys. 2009; 42(1):1-40. DOI: 10.1017/S0033583508004745. View