Development of targeting nanotherapeutics against bladder cancer

膀胱癌靶向纳米疗法的开发

• 批准号: 8442030
• 负责人: CHONG-XIAN PAN
• 金额: --
• 依托单位: VA NORTHERN CALIFORNIA HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8442030
• 关键词: Binding; Biocompatible; Bladder; Blood Cells; Calmette-Guerin Bacillus; Cancer Control; Cancer cell line; Canis familiaris; Cells; Chronic Cystitis; Clinical; Companions; Data; Detection; Development; Doctor of Medicine; Doctor of Philosophy; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Fibroblasts; Funding; Goals; Homing; Human; Image; Immunocompromised Host; K-Series Research Career Programs; Knowledge; Ligands; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of urinary bladder; Mentors; Monitor; Mus; Names; Organ; Paclitaxel; Patients; Peptides; Pharmaceutical Preparations; Pharmacology and Toxicology; Pilot Projects; Site; Specimen; Structure; Surface; System; Therapeutic; Therapeutic Effect; Time; Toxic effect; Treatment Efficacy; Treatment outcome; Urothelial Cell; Vascular Endothelial Cell; Work; Xenograft procedure; cancer cell; density; drug distribution; drug efficacy; improved; in vivo; intravenous injection; nanotherapeutic; novel; outcome forecast; peptide analog; preclinical study; public health relevance; targeted delivery; tumor xenograft

DESCRIPTION (provided by applicant): The goal of this project is to develop a nanomicelle drug delivery system that can specifically target bladder cancer. With the funding of the VA Career Development Award-2 (CDA-2, PI: Pan), a bladder cancer-targeting ligand named PLZ4 was developed. PLZ4 binds to both human and dog bladder cancer cell lines and cancer cells from clinical specimens, suggesting that the pre-clinical studies can be performed in dogs with spontaneous bladder cancer. PLZ4 does not bind to normal urothelial cells, inflamed bladder cells, blood cells, vascular endothelial cells an fibroblasts. Recently, Kit Lam, MD, PhD, (Dr. Pan's VA CDA-2 mentor) developed biocompatible and biodegradable nanomicelles. Chemotherapeutic and imaging agents can be loaded inside the nanomicelles. When they are decorated with PLZ4 on surface, these targeting nanomicelles together with the drug load are delivered into bladder cancer cells. Targeting PLZ4-nanomicelles preferentially concentrate at the bladder cancer xenograft sites in vivo and can significantly prolong survival when compared to non-targeting nanomicelles. In this project, we will optimize the structure of the PLZ4-nanomicelles to achieve the maximal drug loading and delivery, and determine the in vivo targeting and drug distribution in mice carrying bladder cancer xenografts developed from human clinical specimens. A pilot study will be conducted in dog patients carrying spontaneous bladder cancer in order to obtain the preliminary toxicity and efficacy data. PUBLIC HEALTH RELEVANCE: This project aims to develop a multi-functional nanomicelle drug delivery system that can specifically deliver the chemotherapeutic drug paclitaxel to bladder cancer. The nanomicelle system can possibly improve treatment efficacy and lower therapy-associated toxicity.

描述（由申请人提供）：