Cancer cell selective killing nanoparticle for advanced ovarian cancer treatment

癌细胞选择性杀伤纳米颗粒用于晚期卵巢癌治疗

• 批准号: 10680585
• 负责人: Peisheng Xu
• 金额: $ 33.17万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-09 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680585
• 关键词: Affect; Antineoplastic Agents; Apoptosis; Area Under Curve; Autophagocytosis; BCL2 gene; Biodistribution; CASP9 gene; Cancer Etiology; Cancer Patient; Cells; Cessation of life; Chemistry; Chemoresistance; Chemotherapy-Oncologic Procedure; Cisplatin; Clinical; Clinical Trials; Complex; Control Groups; Copper; Data; Death Rate; Degradation Pathway; Deterioration; Development; Diagnosis; Disease; Dose; Drug Kinetics; Drug resistance; Endocytosis; Flow Cytometry; Formulation; Galactose; Half-Life; Head and Neck Cancer; Health; Histologic; Immune; Immune response; Ions; Ligands; Lysosomes; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of ovary; Malignant neoplasm of prostate; Maximum Tolerated Dose; Mediating; Membrane Potentials; Metabolic; Metals; Methods; Modeling; Multi-Drug Resistance; Neoplasm Metastasis; Normal Cell; Operative Surgical Procedures; Oxidation-Reduction; Pathway interactions; Patients; Permeability; Pharmaceutical Preparations; Polymers; Process; Property; Protein Family; Quality of life; Relapse; Research; Resistance; Risk; Serum; Survival Rate; Tumor Debulking; United States; Woman; anti-cancer; cancer cell; cancer drug resistance; cancer therapy; cancer type; cell killing; cytochrome c; density; ethylene glycol; female reproductive system; galactose receptor; human tissue; improved; in vivo; intraperitoneal; malignant breast neoplasm; mitochondrial membrane; mortality; mouse model; multicatalytic endopeptidase complex; nanocomplexes; nanoparticle; novel; novel therapeutic intervention; ovarian neoplasm; public health relevance; response; siRNA delivery; success; systemic toxicity; tool; tumor; tumor growth

PROJECT SUMMARY Ovarian cancer is the fifth most common cause of cancer-related deaths in women and results in more deaths than any other cancer of the female reproductive system. The primary reason for the high death rate of ovarian cancer is multidrug-resistance. Since conventional anticancer drugs cannot kill drug-resistant cells while causing systemic toxicity to deteriorate patient health condition, a novel effective and safe treatment for ovarian cancer is urgently needed. Our preliminary study has discovered a novel polymer-metal combination which uniquely induces a lysosomal copper elevation initiated intrinsic apoptosis pathway. Consequently, this combination is highly selectively in killing cancer cells, including drug-resistant ovarian cancer cells, while not damaging healthy cells. The objective of this research is to develop a polymer-metal nano-complex (PMC) for safe and effective ovarian cancer therapy through a cancer cell selective apoptosis mechanism. Our project has three specific aims. In Aim 1, we will identify the mechanism of cancer cell killing effect of PMC. Aim 2 will identify the cancer selective killing mechanism of PMC and optimize its formulation to achieve the highest selectivity for cancer cells. Aim 3 will investigate the pharmacokinetic properties, examine the biodistribution of PMC, and evaluate its tumor growth inhibitory effect, immune response, and systemic toxicity. In summary, the unique anticancer mechanism of PMC and its simple formulation will provide clinicians a safe and effective tool to control advanced ovarian cancer and benefit ovarian cancer patients.

项目总结