Abstract 4405: Tumor-targeted nanotherapeutics

Abstract

Directing anticancer agents specifically to tumors and/or cancer cells by targeting specific extracellular receptors fulfills the following three most important tasks: (1) preventing or at least substantially limiting adverse side effects on healthy tissues, (2) enhancing drug internalization by cancer cells, and (3) overcoming (at least in part) resistance mechanisms that are based on the active efflux of exogenous drugs from cancer cells. We developed several tumor-targeted nanoscale-based formulations: various nanocarriers (liposomes, lipid nanoparticles, dendrimers, polymers, quantum dots, mesoporous silica and supermagnetic iron oxide nanoparticles); different anticancer drugs (doxorubicin, paclitaxel, camptothecin, and cisplatin); suppressors of cellular drug resistance and tumor grows (antisense oligonucleotides or siRNA targeted to BCL2, MDR1, MRP1, HIF1A, CD44 mRNA); and tumor-targeting agent - luteinizing hormone-releasing hormone (LHRH). The proposed nanotherapeutics were tested in vitro and in vivo using established lung and ovarian cancer cell lines and highly metastatic cancer cells isolated from malignant intraperitoneal ascites from patients with advanced ovarian carcinoma. These cells were used to initiate orthotopic models of lung and ovarian cancers in nude mice that were often accompanied by the development of metastases. Tumor-targeted nanoscale-based drug formulations were delivered intravenously and intraperitoneally (for ovarian cancer) or intravenously and by inhalation (for lung cancer). Treatment with the developed therapeutics led to the suppression of targeted proteins, efficient induction of cell death, effective tumor shrinkage, prevention the development of metastases and limitation of adverse side effects. Acknowledgements: The work was supported by R01CA100098, R01CA111766, and R01CA138533 grants from NIH. Note: This abstract was not presented at the meeting. Citation Format: Olga B. Garbuzenko, Andriy Kuzmov, Justin E. Sapiezynski, Oleh Taratula, Vatsal Shah, Min Zhang, Ronak Savla, Shali John, Lorna Rodriguez-Rodriguez, Tamara Minko. Tumor-targeted nanotherapeutics. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4405. doi:10.1158/1538-7445.AM2015-4405