Targeted chemotherapy delivery and capture

靶向化疗递送和捕获

• 批准号: 9913518
• 负责人: Ali Khademhosseini
• 金额: $ 53.84万
• 依托单位: MAYO CLINIC ARIZONA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-06 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9913518
• 关键词: Address; Angiography; Animal Model; Anthracycline; Antineoplastic Agents; Area; Arteries; Binding; Biocompatible Materials; Biomedical Engineering; Blood Circulation; Bypass; Cancer Model; Cancer Patient; Catheters; Chemistry; Clinical Trials; Community Clinical Oncology Program; DNA; DNA delivery; Dangerousness; Data; Detection; Development; Devices; Dialysis procedure; Disease; Dose; Doxorubicin; Drug Utilization; Drug toxicity; Drug usage; Ensure; Evaluation; Excision; Exposure to; FDA approved; Hematologic Agents; Hemofiltration; Hepatic artery; Iliac Vein; Image; Immunosuppressive Agents; In Vitro; Inferior vena cava structure; Infusion procedures; Interleukin-2; Intravenous; Liver; Malignant Neoplasms; Malignant neoplasm of liver; Malignant neoplasm of lung; Mammary gland; Microspheres; Modeling; Monitor; Oncology; Oryctolagus cuniculus; Patient-Focused Outcomes; Patients; Pelvis; Performance; Perfusion; Pharmaceutical Preparations; Platinum; Prevention; Procedures; Property; Pulmonary veins; Quality of life; Rattus; Risk; Site; Stents; Stream; Surface; Surface Properties; System; Technology; Testing; Therapeutic; Therapeutic Embolization; Thrombolytic Therapy; Time; Topoisomerase Inhibitors; Toxic effect; Treatment Efficacy; Treatment Protocols; Validation; Vascular blood supply; Veins; Venous; antineoplastic antibiotics; base; bronchial artery; chemotherapy; cost; design; drug testing; experience; femoral artery; improved; in vivo; innovation; malignant breast neoplasm; minimally invasive; novel strategies; phase I trial; prevent; prototype; side effect; systemic toxicity; tumor

Abstract Chemotherapy is the major treatment option for cancer patients. However, systemic toxicity from these drugs can significantly impact patient's quality of life and overall survival. Prevention and effective management of side effects of chemotherapy drugs represents a significant bottleneck in oncology today. Many drugs in Phase I trials have been abandoned and many patients have been denied hope from promising treatment regimens because of the associated adverse systemic side effects (4). Furthermore, toxicity from FDA-approved drugs, like interleukin-2, have prevented their use despite having efficacy. To address these limitations of chemotherapy, we propose a transformative technology where the chemotherapy drug is intra-arterially infused from a drug- eluting stent (DES) and captured along the venous outflow of the tumor using an intravascular drug-capturing device (DCD). We believe that by using the DES/DCD pair system, the tumor site will receive highly localized chemotherapy while systemic presence of the excessive drug molecules will be minimized or eliminated (Fig. 1). This strategy can be applied to many cancers, i.e., internal iliac vein/artery for pelvic tumors, bronchial artery/pulmonary vein for lung cancers, internal mammary vein/artery for breast cancer. In this proposal, we will focus on liver cancer because of our liver angiography experience, the liver has a dual blood supply, liver vasculature is large enough to accommodate stent placements and lower cost of imaging, experimentation and maintaining rabbits. As proof of principle, we will use liver cancer as a model to demonstrate the efficacy of this novel strategy, by delivering DNA-targeting anti-cancer drug doxorubicin, which naturally fluoresces at 480 nm allowing easy detection and quantification. Our preliminary data demonstrates exciting results showing our capability in fabrication of anti-thrombotic biomaterials that can selectively release and capture drug molecules. In addition, we have rich experience in catheter-based delivery of biomaterials for a number of in vivo applications, which will ensure successful completion of the proposed project. First we will develop the DES (Aim 1), then develop the DCD (Aim 2) and finally test the drug release and capture concept in rat and rabbit animal models (Aim 3). Successful development of such a system will represent a paradigm shift in the oncology community by improving patient's quality of life, potentially prolonging survival, resurrecting failed Phase I trials from drug toxicity, increasing the use of FDA-approved previously toxic drugs, and opening up new clinical trials to test much higher doses. The proposed idea of drug release and capture represents a platform technology and may have unparalleled impact in other diseases. For example, the system can be designed to isolate exposure to thrombolytic therapy or immunosuppressants.

摘要

项目成果

Engineering hairy cellulose nanocrystals for chemotherapy drug capture.

工程毛状纤维素纳米晶体用于化疗药物捕获。

• DOI: 10.1016/j.mtchem.2021.100711
• 发表时间: 2022
• 期刊: Materials today. Chemistry
• 作者: Young,SarahAE;Muthami,Joy;Pitcher,Mica;Antovski,Petar;Wamea,Patricia;Murphy,RobertDenis;Haghniaz,Reihaneh;Schmidt,Andrew;Clark,Samuel;Khademhosseini,Ali;Sheikhi,Amir
• 通讯作者: Sheikhi,Amir