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Theranostic gold nanoparticles for imaged-guided radical prostatectomy and PDT ablation

用于影像引导根治性前列腺切除术和 PDT 消融的治疗诊断金纳米颗粒

基本信息

批准号：
9207085
负责人：
James Peter Basilion
金额：
$ 66.42万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-19 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9207085
关键词：
Ablation Advanced Malignant Neoplasm Adverse effects Affinity Antigen Targeting Automobile Driving Awareness Binding Biocompatible Materials Biodistribution Biological Markers Blood Cancerous Canis familiaris Cells Cellular Membrane Clinical Complex Conventional Surgery Data Decision Making Development Diagnosis Diagnostic Disease Dose Engineering Ensure Erectile dysfunction Excision Extracapsular FOLH1 gene Free Radicals Future Generations Goals Gold Hydrophobicity Image Image-Guided Surgery Implant Impotence In Vitro Incidence Incontinence Injectable Intervention Length Ligands Light Localized Disease Malignant Neoplasms Malignant neoplasm of prostate Methods Modeling Modern Medicine Morbidity - disease rate Mus Muscle Nanotechnology Nerve Normal tissue morphology Nude Mice Operative Surgical Procedures Organ PSA screening PUVA Photochemotherapy Patient observation Patients Pharmaceutical Preparations Property Prostate Prostatectomy Prostatic Neoplasms Qualifying Quality of Care Radiation therapy Radical Prostatectomy Recurrence Research Serum Staging Structure Structure of capsule of prostate Surgeon Technology Testing Therapeutic Therapeutic Agents Therapeutic Intervention Time Tissues Treatment Efficacy Tumor Tissue United States Urethral sphincter cancer cell cancer diagnosis cell killing cellular imaging clinical translation digital disease diagnosis ex vivo imaging exhaust experience image guided improved in vivo innovation killings men mitochondrial membrane nanoparticle novel prostate cancer cell prostate cancer cell line public health relevance rectal screening success theranostics tumor tumor eradication uptake

项目摘要

DESCRIPTION (provided by applicant): Prostate cancer is the most prevalent diagnosed disease among men in the United States. Currently diagnosis is achieved through assessment of multiple data including PSA blood levels and digital rectal exams. Since the introduction of PSA testing significantly more men have been diagnosed and treated for the disease. The course of therapeutic action for diagnosed prostate cancer depends on staging of the disease and breaks down to essentially 3 interventions depending on stage: 1) Radical prostatectomy for cancers that are contained within the prostate; 2) Radiation therapy which can be used for both early and more advanced cancer; and 3) Watchful waiting, or active surveillance. With current screening and public awareness approximately 91% of prostate cancers detected are estimated to be clinically localized when first detected and potentially these patients are candidates for surgery, which is only used for localized disease. However, there is no way to know with certainty if the cancer is localized within the prostate capsule during surgery, and, of the patients that undergo radical prostatectomy, approximately 20% do not achieve surgical cures because of disease spread outside of the prostate gland. Moreover, surgery is associated with significant morbidities including incontinence and erectile dysfunction. The need to perform more complete prostatectomies and reduce surgical morbidities defines an unmet clinical need. The development of a technology that would improve the ability of the surgeon to distinguish among these structures, assess extra-capsular invasion of the cancer during prostatectomy, improve surgical decisions, and ablate cancer tissue that is not resectable, would improve quality of care. We propose to use a highly selective prostate biomarker, PSMA, to drive the binding of a targeted theranostic nanoparticle agent to prostate cancer. This nanoparticle contains a photodynamic therapeutic agent, Pc4 that is both fluorescent and a potent cancer therapeutic. The goal of the proposed studies is to derivatize the nanoparticle containing Pc4 with a ligand for PSMA, thusly driving its selective uptake and delivery of Pc4 into prostate tumors. During surgery the fluorescent aspects of Pc4 would be exploited to visually differentiate the tumor from surrounding normal tissues, which do not take up the nanoparticle. This would allow the surgeon to decide in real time how aggressive the surgical intervention need be, i.e. the degree of morbidity potentially incurred to fully remove diseased tissues. Upon completion of the surgical resection, light of a specific wavelength can be used to excite the Pc4 resulting in free radical generation and robust cancer killing of the remaining cancer tissues that were not removed by the surgical procedure.