Developing targeted therapy with prostate cancer specific nanomedicine

开发前列腺癌特异性纳米药物的靶向治疗

• 批准号: 8615933
• 负责人: Jer-Tsong Hsieh
• 金额: $ 32.79万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8615933
• 关键词: Ablation; Address; Adverse effects; Affinity; Age; Aging; American; Androgens; Animal Model; Antineoplastic Agents; Area; Biocompatible; Biocompatible Materials; Cancer Patient; Castration; Cell Death; Cell model; Cells; Clinical; DNA Damage; Detection; Development; Disease; Drug Delivery Systems; Drug resistance; Engineering; FDA approved; Goals; Heterogeneity; Image; Investigational Therapies; Kidney; Knowledge; Left; Legal patent; Liver; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of prostate; Medicine; Metastatic Lesion; Metastatic Prostate Cancer; Modeling; Monitor; Mus; Mutagens; Nanotechnology; Neoplasm Metastasis; Outcome; Outcome Study; Patients; Peptides; Phenotype; Polymers; Prevention; Property; Prostatic Neoplasms; Quality of life; R peptide; Radiation; Recurrence; Regimen; Reporting; Research; Resistance; Solid Neoplasm; Specificity; Spleen; Structure of base of prostate; System; Technology; Therapeutic; Therapeutic Agents; Time; Treatment Efficacy; base; biodegradable polymer; cancer cell; cancer initiation; cancer recurrence; cancer stem cell; cancer therapy; castration resistant prostate cancer; cell type; chemotherapeutic agent; chemotherapy; combat; cytolethal distending toxin; deprivation; design; early onset; effective therapy; fluorescence imaging; improved; in vivo; innovation; intravenous injection; killings; men; molecular imaging; mortality; nanomedicine; nanoparticle; neoplastic cell; novel therapeutics; physical conditioning; poly(lactide); pre-clinical; prevent; prostate cancer cell; public health relevance; response; self-renewal; stem cell population; stem cells; theories; therapy development; tumor; tumor progression; uptake

Project Summary Prostate cancer (PCa) has surpassed lung cancer as the leading cancer among American men. The majority of patients have already developed metastatic lesions at initial clinical presentation and androgen ablation has become a standard therapy because PCa is an androgen-dependent (AD) disease. Inevitably, the recurrence of castration resistant PCa (CRPC) will result in mortality of patients since CRPC cells are resistant to conventional chemotherapy. Moreover, because of high age, PCa patients often do not have favorable physical conditions to tolerate undesirable side effects of chemotherapy. Thus, developing a new, safe and effective therapy becomes a high priority. Although PCa patient survival with newly developed therapeutic regimens has been significantly improved, PCa remains incurable. One of the possible theories to explain the recurrence and ineffectiveness of cancer treatment is the cancer stem cell (CSC) model in which a subset of tumor cells is responsible for cancer initiation and progression as well as cancer recurrence. These CSCs share with normal stem cells the properties of self-renewal, immortal and differentiation into a variety of cell types including heterogeneous lineages of cancer cells. Also, CSC can re-grow from a few cells left behind after therapy, it will be important to develop therapies that are more specifically directed against CSCs. Thus, targeting cancer stem cell is now becomes an active research area of cancer therapy to achieve the ultimate cure. In order to target PCa specifically, we are developing a new biodegradable and biocompatible nanoparticle that can target PCa specifically with imaging capabilities. Using this unique delivery system, we propose to engineer a unique genotoxin that can preferentially kill PCa cells expressing stem cell properties then evaluate the therapeutic efficacy of PCa monitored by molecular imaging in pre-clinical animal models. We expect be able to monitor the drug delivery and/or response of cancer cells in a real-time manner. This experimental therapy could become a better regimen for treating CRPC because this agent has a PCa specificity, which is expected to be less toxic than chemotherapeutic agents. Most importantly, this proposal is to explore a new avenue of tailored therapy in contrast to conventional therapeutic strategy; we expect that the outcome of this study should have an immediate clinical impact on CRPC therapy.

项目摘要 前列腺癌（PCa）已超过肺癌成为美国男性的主要癌症。 大多数患者在初始临床表现时已经发生转移性病变， 雄激素消融已成为标准疗法，因为PCa是雄激素依赖性（AD） 疾病去势抵抗性前列腺癌（CRPC）的复发不可避免地会导致患者的死亡 因为CRPC细胞对常规化疗有抗性。此外，由于年龄大，PCa 患者通常不具有良好的身体状况以耐受药物的不良副作用。 化疗因此，开发一种新的、安全有效的治疗方法成为当务之急。 尽管新开发的治疗方案对PCa患者的生存率有显著影响， 虽然有所改善，但PCa仍然无法治愈。一个可能的理论来解释复发和 癌症治疗无效的另一个例子是癌症干细胞（CSC）模型，其中肿瘤干细胞亚群（A1）和肿瘤干细胞亚群（A2）在肿瘤干细胞（CSC）模型中表达。 细胞负责癌症的起始和进展以及癌症复发。这些CSC 与正常干细胞一样，具有自我更新、永生和分化成各种细胞的特性。 细胞类型，包括癌细胞的异质谱系。此外，CSC可以从少数细胞重新生长 治疗后留下的，重要的是要开发更具体的治疗方法， 针对CSC。因此，靶向治疗肿瘤干细胞已成为肿瘤研究的一个热点 治疗以达到最终治愈。为了专门针对PCa，我们正在开发新的 生物可降解和生物相容的纳米颗粒，可以特异性靶向PCa与成像能力。 使用这种独特的传递系统，我们建议设计一种独特的基因毒素， 杀死表达干细胞特性的PCa细胞，然后评估监测的PCa的治疗效果 在临床前动物模型中进行分子成像。我们希望能够监控药物的输送 和/或癌细胞的反应。这种实验性疗法可能成为 治疗CRPC的更好方案，因为该药物具有PCa特异性，预计 毒性低于化疗药物。最重要的是，这一建议是为了探索一条新的途径， 与常规治疗策略相比，定制治疗;我们预计， 研究应该对CRPC治疗产生直接的临床影响。