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.

抽象的 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， 可以以微创的方式注入转移引起的骨变性位点 癌症，再生骨骼并阻止疼痛。转移是癌症死亡的主要原因。骨头是 最常见的癌症转移性部位。每年大约有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有效地破坏骨骼。容易脆弱的骨头 通过简单运动骨折，导致腹部疼痛和对骨转移患者的动静。作为 结果，骨转移患者的寿命质量极为差。 骨转移目前无法治愈。在诊所中，聚合物甲基丙烯酸甲酯（PMMA）水泥为 主要用于立即稳定垂死的癌症患者的转移引起的骨骼碎片以减少 根据其出色的机械强度，它们的毁灭性疼痛。但是，PMMA是没有的有机玻璃 再生骨骼，并具有严重不良事件的高风险。随着癌症疗法正在迅速发展， 骨转移患者的寿命比以前更长。因此，有紧急且未满足的医疗需求 对于可以支持癌症患者健康恢复的高级水泥。克服 PMMA水泥，磷酸钙水泥已根据其相似的 天然骨骼的组成。但是，现有的磷酸钙水泥产物破裂释放药物，无 他们中的用于药物输送目的获得了FDA批准。 为了解决这个重要的医疗问题，我们旨在开发一种范式转移的“治愈水泥” 可以通过使用创新的Whitloctite材料提供抗癌药物并再生骨骼。 Whitlockite是 人体中第二大最丰富的骨矿物质，年轻人的比例更高 以及矿化的早期阶段。我们的团队已经开发了一种大规模的，轻松的惠特洛基的合成方法 并显示出与现有钙相比的优势骨再生能力和机械强度 诊所中的磷酸盐替代产物。最近，令人兴奋的是，我们提出了合成过程 Whitlockite并开发了可注射的基于惠特洛锁的水泥。令人惊讶的是，这个高级基于惠特洛基石 水泥可以加载大量的药物，并以持续的方式释放它们。基于此 创新意图，通过这个NIH STTR计划，我们旨在生产第一个反癌药物 骨水泥产物并将其转化为诊所以使骨转移患者受益。我们设想我们的 创新的抗癌药物递送基于惠特洛锁的骨水泥产品将为 克服骨转移。我们还希望这种基于whitlockite的骨水泥将大大减少侧面 抗癌药对其他器官的影响，通过对骨骼进行靶向疗法。