Next generation anti-cancer drugdelivering cement for bone metastasis patients

摘要 我们的使命是为骨转移患者开发一种新型抗癌药物骨水泥， 其可以以微创方式注射到转移引起的骨退化部位， 癌症，再生骨骼，停止疼痛。转移是癌症死亡的主要原因。骨头是其中一个 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而广泛地破坏骨。易碎骨 由于简单的运动而骨折，导致骨转移患者无法忍受的疼痛和无法移动。作为 骨转移患者的生活质量极差。 骨转移目前是无法治愈的。在临床上，聚甲基丙烯酸甲酯（PMMA）骨水泥是 主要用于立即稳定垂死癌症患者的转移引起的骨折， 他们的毁灭性的痛苦，基于其出色的机械强度。然而，PMMA是有机玻璃， 再生骨，严重不良事件的风险高。随着癌症疗法的迅速发展， 骨转移患者的寿命比以前更长。因此，有一个迫切的和未满足的医疗需求， 一种先进的水泥，可以支持癌症患者的健康恢复。为了克服…的缺点 PMMA骨水泥，磷酸钙骨水泥已用于骨再生的基础上，其类似 成分与天然骨骼结合。然而，现有的磷酸钙骨水泥产品突释药物和无 他们中的一些人获得了FDA的药物输送批准。 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“愈合水泥”， 可以通过使用创新的白洛克石材料来输送抗癌药物和再生骨。白磷钙石是 人体中第二丰富的骨矿物质，在年轻人中比例较高 早期成矿作用。本课题组开发了一种大规模、简便的白磷钾石合成方法 并显示出其上级的骨再生能力和机械强度相比，现有的钙 磷酸盐骨替代产品在临床上。最近，令人兴奋的是，我们改进了合成方法， 并开发了一种可注射的白磷钾石基水泥。引人注目的是，这种先进的基于白洛克石的 水泥可以装载大量的药物并以持续的方式释放它们。基于此 创新的发明，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。我们设想， 创新性抗癌药物递送白磷钾石基骨水泥产品将提供突破， 克服骨转移。我们还预计这种基于白磷钾石的骨水泥将显著减少 通过对骨骼进行靶向治疗，减少抗癌药物对其他器官的影响。

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.