Next generation anti-cancer drugdelivering cement for bone metastasis patients

用于骨转移患者的下一代抗癌药物输送水泥

• 批准号: 10483954
• 负责人: Hae Lin Jang
• 金额: $ 40万
• 依托单位: CURER INC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483954
• 关键词: Address; Alpha Particles; American; Antineoplastic Agents; Antitumor Drug Screening Assays; Area; Binding; Bone Growth; Bone Pain; Bone Regeneration; Bone Substitutes; Bone Tissue; Cancer Etiology; Cancer Patient; Cell Survival; Cessation of life; Clinic; Clinical; Data; Disseminated Malignant Neoplasm; Dose; Drug Delivery Systems; Drug toxicity; Engineering; FDA approved; Food and Drug Administration Drug Approval; Formulation; Fracture; Health; Hospitals; Human; Human body; Hydroxyapatites; In Vitro; Injectable; Licensing; Life; Malignant Neoplasms; Mechanics; Medical; Medical Device; Metastatic Neoplasm to the Bone; Methods; Minerals; Mission; Movement; Neoplasm Metastasis; Notification; Organ; Osteoclasts; Osteolysis; Osteolytic; Osteoporosis; Paget' s Disease; Pain; Particle Size; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Plexiglass; Polymethyl Methacrylate; Positioning Attribute; Preclinical Testing; Preparation; Process; Production; Quality of life; Recovery Support; Regenerative capacity; Research; Risk Assessment; Serious Adverse Event; Site; Small Business Technology Transfer Research; Standardization; Sterilization; Surface; System; Technology; Therapeutic; Time; Toxic effect; Translating; Translations; United States National Institutes of Health; Validation; Woman; aged; anti-cancer; base; biomaterial compatibility; bone; bone fragility; bone health; calcium phosphate; cancer cell; commercialization; developmental toxicity; effective therapy; efficacy testing; experience; healing; high risk; implant material; in vivo; in vivo Model; innovation; invention; medical schools; meetings; mid-career faculty; mimetics; mineralization; minimally invasive; monomer; nanomedicine; nanoparticle; neoplastic cell; next generation; novel; pain reduction; particle; polymerization; pre-clinical; prevent; professor; programs; prototype; reproductive; scale up; side effect; systemic toxicity; targeted treatment; tumor progression

Abstract Our mission is to develop an innovative anti-cancer drug delivering bone cement for bone metastasis patients, which can be injected into metastasis-caused bone degeneration sites in a minimally invasive manner, to regress cancer, regenerate bone, and stop the pain. Metastasis is the main cause of cancer death. Bone is one of the most frequent cancer metastatic sites. About 350,000 Americans die due to bone metastasis each year. Metastasized cancer cells can extensively destroy the bone by over-activating osteoclasts. Fragilized bone easily gets fractured by simple movement, causing intolerable pain and immobility to bone metastasis patients. As a result, the life quality of bone metastasis patients is extremely poor. Bone metastasis is currently incurable. In the clinic, polymethyl methacrylate (PMMA) cement is dominantly used to instantly stabilize the metastasis-caused bone fractures of dying cancer patients to reduce their devastating pain, based on its excellent mechanical strength. However, PMMA is plexiglass that does not regenerate bone and has a high risk of serious adverse events. As cancer therapeutics are rapidly advancing, bone metastasis patients are living longer than before. Therefore, there is an urgent and unmet medical need for an advanced cement that can support the recovery of cancer patient health. To overcome the drawbacks of PMMA cement, calcium phosphate cement has been used for bone regeneration based on its similar composition to native bone. However, existing calcium phosphate cement products burst release drugs and none of them received FDA approval for drug delivery purposes. To solve this important medical problem, we aim to develop a paradigm-shifting “healing cement” that can deliver anti-cancer drugs and regenerate bone by using innovative whitlockite material. Whitlockite is the second most abundant bone mineral in the human body, which exists with a higher ratio in younger aged people and earlier stage of mineralization. Our team has developed a large scale, facile synthetic method of whitlockite and showed its superior bone regeneration capacity and mechanical strength compared to existing calcium phosphate bone substitute products in the clinic. Recently, excitingly, we advanced the synthetic process of whitlockite and developed an injectable whitlockite-based cement. Strikingly, this advanced whitlockite-based cement could load a significantly large quantity of drugs and release them in a sustained manner. Based on this innovative invention, through this NIH STTR program, we aim to manufacture the first anti-cancer drug delivering bone cement product and translate it into the clinic to benefit bone metastasis patients. We envision that our innovative anti-cancer drug delivering whitlockite-based bone cement product will provide a breakthrough to overcome bone metastasis. We also expect this whitlockite-based bone cement will significantly reduce the side effects of anti-cancer drugs on other organs by enabling targeted therapy to the bone.

摘要 我们的使命是开发一种创新的抗癌药物，为骨转移患者提供骨水泥， 它可以以微创的方式注射到转移引起的骨变性部位，以消退 癌症，再生骨骼，止痛。转移是癌症死亡的主要原因。骨头是其中之一 最常见的癌症转移部位。每年约有35万美国人死于骨转移。 转移的癌细胞可以通过过度激活破骨细胞来广泛地破坏骨骼。容易脆化的骨头 通过简单的运动就会骨折，给骨转移患者带来难以忍受的疼痛和不能动弹。作为一名 结果，骨转移患者的生活质量极差。 骨转移目前是不治之症。在临床上，聚甲基丙烯酸甲酯(PMMA)水泥是 主要用于即时稳定因转移引起的骨折，使临终癌症患者的骨折复位 他们毁灭性的痛苦，基于其出色的机械强度。然而，PMMA是有机玻璃，不会 会再生骨骼，并且有很高的严重不良事件风险。随着癌症治疗技术的迅速发展， 骨转移患者的寿命比以前更长了。因此，有一个紧急的和未得到满足的医疗需求。 对于一种先进的水泥，可以支持癌症患者的健康恢复。克服……的缺点 聚甲基丙烯酸甲酯骨水泥、磷酸钙骨水泥基于其相似的特性已被用于骨再生 天然骨骼的成分。然而，现有的磷酸钙骨水泥产品爆裂释放药物，而且没有 其中一些药物获得了FDA的批准，可用于药物输送。 为了解决这一重要的医学问题，我们的目标是开发一种改变范式的“治愈水泥”，它 可以提供抗癌药物，并通过使用创新的白锁石材料再生骨骼。惠特洛克是 人体内第二丰富的骨矿物质，在年轻人中的比例较高 成矿早期。我们团队已经开发出一种大规模、简便的白锁石合成方法。 与现有的钙相比，它具有更好的骨再生能力和机械强度。 临床上应用的磷酸盐骨替代产品。最近，令人兴奋的是，我们改进了合成工艺 并开发了一种可注射的白锁石基水泥。引人注目的是，这种先进的基于白色锁石的 水泥可以装载大量药物并以持续的方式释放它们。在此基础上 创新发明，通过这项NIH STTR计划，我们的目标是制造第一种抗癌药物递送 骨水泥产品并将其转化为临床，造福骨转移患者。我们设想我们的 创新抗癌药物推出白锁石基骨水泥产品将为 克服骨转移。我们还预计，这种以白色锁石为基础的骨水泥将显著减少侧面 通过对骨骼进行靶向治疗，抗癌药物对其他器官的影响。