R&D-OTHER SCIENCES-B RES

吉西他滨（Gemzar(R)）是一种有效的化疗药物，被批准用于治疗多种癌症，包括非小细胞肺癌（NSCLC）、胰腺癌、乳腺癌和卵巢癌。然而，由于其半衰期短和显著的全身毒性，其使用受到限制。本研究利用一种新型脂质-磷酸钙（LCP）纳米粒子平台设计多功能靶向纳米粒子（NP），将吉西他滨三磷酸（GTP）和111铟递送至癌细胞。在这些新型颗粒中，GTP是治疗剂，111铟是放射显像剂。这些lcp - gtp -铟治疗纳米颗粒将被评估在肺肿瘤模型中的疗效和成像能力。新的NPs还将在正常小鼠中进行初步毒性评估。靶向lcp - gtp -铟治疗纳米颗粒有望增加吉西他滨的半衰期，降低毒性，同时允许肿瘤成像能力。GTP+铟纳米颗粒的开发将改善已知化疗药物的递送，并增强该药物在肺癌和其他癌症中扩大使用的潜力。此外，铟将允许在不影响NP特征或生物分布的情况下对NP进行体内跟踪和成像。这种诊断能力将使基于生物分布的个体化治疗成为可能，从而产生真正的个性化医疗产品。

Gemcitabine (Gemzar(R)) is an effective chemotherapeutic drug approved for treatment of several cancers, including non-small cell lung cancer (NSCLC), pancreatic, breast and ovarian cancer. However, its use has been limited due to its short half-life and significant systemic toxicity. This proposal utilizes a novel Lipid-Calcium-Phosphate (LCP) nanoparticle platform for the design of multifunctional targeted nanoparticles (NP) to deliver gemcitabine triphosphate (GTP) and 111Indium to cancer cells. In these novel particles GTP is a therapeutic agent and 111Indium is a radio-imaging agent. These resulting LCP-GTP-Indium theranostic nanoparticles will be evaluated for efficacy in lung tumor models and imaging capabilities. The novel NPs will also be evaluated for preliminary toxicity in normal mice. The targeted LCP-GTP-Indium theranostic nanoparticles are expected to increase the half-fife and lower the toxicity of gemcitabine while simultaneously allowing for tumor imaging capabilities. Development of GTP+lndium nanoparticles will improve the delivery of a known chemotherapy drug and enhance the potential for expanded use of this drug in lung and other cancers. Furthermore 111Indium will allow in vivo tracking and imaging of NP without affecting the NP characteristics or biodistribution. This diagnostic capability will enable individualized treatment based on biodistribution, leading to a true personalized medicine product.