Development of targeting nanotherapeutics against bladder cancer

膀胱癌靶向纳米疗法的开发

• 批准号: 9275369
• 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/9275369
• 关键词: BCG Vaccine; Binding; Bladder; Blood Cells; Cancer Control; Cancer cell line; Canis familiaris; Cells; Chronic Cystitis; Clinical; Companions; Data; Development; Doctor of Medicine; Doctor of Philosophy; Drug Delivery Systems; Drug Kinetics; Drug Monitoring; Fibroblasts; Formulation; Funding; Goals; Homing; Human; Immunocompromised Host; K-Series Research Career Programs; Knowledge; Ligands; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of urinary bladder; Mentors; Mus; Names; Organ; Paclitaxel; Patients; Peptides; Pharmaceutical Preparations; Pharmacology and Toxicology; Pilot Projects; Site; Specimen; Structure; Surface; System; Therapeutic; Therapeutic Agents; Therapeutic Effect; Time; Toxic effect; Treatment Efficacy; Treatment outcome; Treatment-related toxicity; Urothelial Cell; Vascular Endothelial Cell; Work; Xenograft procedure; biomaterial compatibility; cancer cell; chemotherapeutic agent; density; drug distribution; drug efficacy; imaging agent; imaging detection; imaging potential; improved; in vivo; intravenous injection; nanotherapeutic; novel; outcome forecast; peptide analog; preclinical study; 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.

描述（由申请人提供）： 该项目的目的是开发一种可以专门针对膀胱癌的纳米胶药输送系统。随着VA职业发展奖2（CDA-2，PI：PAN）的资助，开发了一个名为PLZ4的膀胱癌靶向配体。 PLZ4与临床标本中的人和狗膀胱癌细胞系和癌细胞结合，这表明可以在自发性膀胱癌的狗中进行临床前研究。 PLZ4不与正常的尿路上皮细胞，发炎的膀胱细胞，血细胞，血管内皮细胞和成纤维细胞结合。最近，医学博士Kit Lam（Pan博士的VA CDA-2 Mentor）开发了生物相容性且可生物降解的纳米细胞。 化学治疗剂和成像剂可以在纳米细胞内加载。当它们在表面上用PLZ4装饰时，这些靶向纳米细胞以及药物负荷被输送到膀胱癌细胞中。靶向PLZ4-纳米细胞优先将体内的膀胱癌异种移植部位浓缩，并且与非靶向纳米细胞相比，可以显着延长生存率。在该项目中，我们将优化PLZ4-纳米细胞的结构，以实现最大的药物载荷和递送，并确定携带膀胱癌异种移植物的小鼠体内靶向和药物分布。将对携带自发膀胱癌的狗患者进行一项试点研究，以获得初步的毒性和功效数据。

项目成果

The differential expression of EphB2 and EphB4 receptor kinases in normal bladder and in transitional cell carcinoma of the bladder.

• DOI: 10.1371/journal.pone.0105326
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Li X;Choi WW;Yan R;Yu H;Krasnoperov V;Kumar SR;Schuckman A;Klumpp DJ;Pan CX;Quinn D;Gill IS;Gill PS;Liu R
• 通讯作者: Liu R