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

基本信息

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
项目类别：
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&apos 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

项目摘要

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，可以以微创方式注射到转移引起的骨退变部位，以消退癌症、再生骨骼和停止疼痛是癌症死亡的主要原因之一。最常见的癌症转移部位，每年约有 350,000 名美国人死于骨转移。转移的癌细胞主要通过过度激活破骨细胞来破坏骨骼，从而容易使骨骼脆弱。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无法活动。导致骨转移患者的生活质量极差。骨转移目前在临床上是无法治愈的。用于立即稳定垂死癌症患者因转移引起的骨折，以减少它们具有毁灭性的疼痛，这是基于其优异的机械强度。然而，PMMA 是有机玻璃，却不会。随着癌症治疗的迅速发展，骨骼再生并具有很高的严重不良事件风险。骨转移患者的寿命比以前更长，因此存在迫切且未得到满足的医疗需求。寻找一种可以支持癌症患者健康恢复的先进水泥。 PMMA骨水泥、磷酸钙骨水泥基于其类似的优点已被用于骨再生然而，现有的磷酸钙骨水泥产品没有突释药物。其中其中一些已获得 FDA 批准用于药物输送。为了解决这一重要的医学问题，我们的目标是开发一种范式转变的“愈合水泥”，可以通过使用创新的白铁矿材料来输送抗癌药物并再生骨骼。人体内第二丰富的骨矿物质，在年轻人中比例较高我们的团队开发了一种大规模、简便的白磷矿合成方法。与现有的钙相比，显示出其优越的骨再生能力和机械强度最近，令人兴奋的是，我们推进了磷酸盐骨替代产品的合成工艺。并开发了一种可注射的白磷矿基水泥，引人注目的是，这种先进的白磷矿基水泥。水泥可以装载大量药物并持续释放。创新发明，通过这个 NIH STTR 计划，我们的目标是制造第一个抗癌药物输送骨水泥产品并将其转化为临床以造福骨转移患者。创新抗癌药物提供基于白铁矿的骨水泥产品将为以下领域提供突破：我们还预计这种基于白磷矿的骨水泥将显着减少骨转移。通过对骨骼进行靶向治疗来消除抗癌药物对其他器官的影响。