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Lectin Mediated Biorecognition as a Novel Strategy for Targeted Delivery to Bladder Cancer

2011; Lippincott Williams & Wilkins; Volume: 186; Issue: 4 Linguagem: Inglês

10.1016/j.juro.2011.05.040

1527-3792

Lukas Neutsch, Verena E. Plattner, Sonja Polster-Wildhofen, Agnes Zidar, Andreas Chott, Gerrit Borchard, O. Zechner, Franz Gabor, Michael Wirth,

Urological Disorders and Treatments

No AccessJournal of UrologyInvestigative Urology1 Oct 2011Lectin Mediated Biorecognition as a Novel Strategy for Targeted Delivery to Bladder Cancer Lukas Neutsch, Verena E. Plattner, Sonja Polster-Wildhofen, Agnes Zidar, Andreas Chott, Gerrit Borchard, Othmar Zechner, Franz Gabor, and Michael Wirth Lukas NeutschLukas Neutsch Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Austria , Verena E. PlattnerVerena E. Plattner Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Austria , Sonja Polster-WildhofenSonja Polster-Wildhofen Department of Urology, Wilhelminenspital, Vienna, Austria , Agnes ZidarAgnes Zidar Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Austria , Andreas ChottAndreas Chott Department of Pathology and Microbiology, Wilhelminenspital, Vienna, Austria , Gerrit BorchardGerrit Borchard Laboratory of Pharmaceutics and Biopharmaceutics, University of Geneva, Switzerland , Othmar ZechnerOthmar Zechner Department of Urology, Wilhelminenspital, Vienna, Austria , Franz GaborFranz Gabor Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Austria , and Michael WirthMichael Wirth Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Austria View All Author Informationhttps://doi.org/10.1016/j.juro.2011.05.040AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Inadequate urothelial delivery of drugs is considered a primary cause of current shortcomings in adjuvant intravesical chemotherapy for bladder cancer. We report what is to our knowledge a novel biorecognitive approach to achieve more regionally selective targeting of malignant tissue and improve urothelial uptake based on specific interaction between lectins and bladder cell glycocalyces. Materials and Methods: We assessed the cytoadhesive and cytoinvasive potential of selected plant lectins in 3 human urothelial cell lines, corresponding to healthy tissue, and low and high grade carcinoma, respectively. Flow cytometry and fluorimetry were used to determine binding capacity and specificity in single cells and confluent monolayers. Monensin quenching experiments, microscopic analysis and enzyme treatment allowed further characterization of internalization, the uptake pathway and the potential cause of tumor selectivity. Results: Wheat germ agglutinin had the highest bioadhesive potential while peanut agglutinin was the most potent discriminator between healthy and cancerous tissue (p <0.01). In each case cell interaction was highly specific (greater than 80%) and proved decisive for efficient uptake. Within 60 minutes after exposure greater than 50% of membrane bound lectins were internalized in acidic compartments. Cancer associated aberrant glycosylation likely represents the determining cause of peanut agglutinin selectivity. Conclusions: Given careful choice of the targeting ligand, the development of carbohydrate based delivery strategies for bladder cancer therapy seems feasible. Lectin bioadhesion may not only mediate preferential accumulation in malignant tissue but also promote cellular internalization via increased recruitment of membrane bound material to physiological uptake routes. References 1 : Guideline for the management of nonmuscle invasive bladder cancer (stages Ta, T1, and Tis): 2007 update. J Urol2007; 178: 2314. 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Google Scholar © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 186Issue 4October 2011Page: 1481-1488 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Keywordscarcinomaurinary bladderintravesicaladministrationlectinsdrug delivery systemsMetricsAuthor Information Lukas Neutsch Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Austria More articles by this author Verena E. Plattner Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Austria More articles by this author Sonja Polster-Wildhofen Department of Urology, Wilhelminenspital, Vienna, Austria More articles by this author Agnes Zidar Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Austria More articles by this author Andreas Chott Department of Pathology and Microbiology, Wilhelminenspital, Vienna, Austria More articles by this author Gerrit Borchard Laboratory of Pharmaceutics and Biopharmaceutics, University of Geneva, Switzerland More articles by this author Othmar Zechner Department of Urology, Wilhelminenspital, Vienna, Austria More articles by this author Franz Gabor Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Austria More articles by this author Michael Wirth Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Austria More articles by this author Expand All Advertisement PDF downloadLoading ...