R&D-OTHER SCIENCES-B RES

吉西他滨（健择））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。该提案利用新型脂质-磷酸钙（LCP）纳米颗粒平台来设计多功能靶向纳米颗粒（NP），以将吉西他滨三磷酸（GTP）和111铟递送至癌细胞。在这些新颗粒中，GTP是治疗剂，111铟是放射成像剂。将评估这些所得LCP-GTP-铟治疗诊断纳米颗粒在肺肿瘤模型中的功效和成像能力。还将评估新NP在正常小鼠中的初步毒性。预期靶向LCP-GTP-铟治疗诊断纳米颗粒增加吉西他滨的半衰期并降低其毒性，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展使用的潜力。此外，111铟将允许NP的体内跟踪和成像，而不影响NP特性或生物分布。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药物产品。

Gemcitabine (Gemzar¿) 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.