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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.

描述（由申请人提供）：前列腺癌是美国男性中最常见的诊断疾病。目前诊断是通过评估多种数据来实现的，包括 PSA 血液水平和直肠指检。自从引入 PSA 检测以来，越来越多的男性被诊断出患有这种疾病并接受治疗。诊断出的前列腺癌的治疗过程取决于疾病的分期，并根据分期分为 3 种干预措施： 1) 针对前列腺内癌症的根治性前列腺切除术； 2）放射治疗，可用于早期和晚期癌症； 3) 观察等待，或主动监视。根据目前的筛查和公众意识，大约 91% 的前列腺癌在首次检测时估计是临床局限性的，这些患者可能是手术的候选者，手术仅用于局部疾病。然而，在手术过程中无法确定癌症是否局限于前列腺包膜内，并且在接受根治性前列腺切除术的患者中，大约 20% 由于疾病扩散到前列腺外而未能实现手术治愈。此外，手术与严重的发病率相关，包括失禁和勃起功能障碍。进行更完整的前列腺切除术和减少手术发病率的需要定义了未满足的临床需求。开发一种技术可以提高外科医生区分这些结构的能力，评估前列腺切除术期间癌症的囊外侵犯，改善手术决策，并消融不可切除的癌症组织，这将提高护理质量。我们建议使用高度选择性的前列腺生物标志物 PSMA 来驱动靶向治疗诊断纳米颗粒剂与前列腺癌的结合。这种纳米颗粒含有光动力治疗剂 Pc4，它既具有荧光性，又是一种有效的癌症治疗剂。拟议研究的目标是用 PSMA 配体衍生化含有 Pc4 的纳米颗粒，从而驱动其选择性摄取并将 Pc4 递送到前列腺肿瘤中。在手术过程中，将利用 Pc4 的荧光特性在视觉上将肿瘤与周围正常组织区分开来，而周围正常组织不会吸收纳米颗粒。这将使外科医生能够实时决定手术干预需要多大程度，即完全切除病变组织可能导致的发病程度。手术切除完成后，可以使用特定波长的光来激发 Pc4，从而产生自由基并强力杀死剩余的癌症组织，从而消除癌症。没有通过外科手术去除。