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奥曲肽纳米粒对体内诱导的 MIA Paca-2 胰腺导管腺癌具有亲和力,这种肿瘤类似于胰腺远侧的胰腺多肽分泌肿瘤 (PPoma)。

Octreotide Nanoparticles Showed Affinity for In Vivo MIA Paca-2 Inducted Pancreas Ductal Adenocarcinoma Mimicking Pancreatic Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma).

机构信息

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro, Brazil.

Centro de Radiofarmácia, Instituto de Pesquisas Energéticas e Nucleares, São Paulo, Brazil.

出版信息

Pharm Res. 2019 Aug 5;36(10):143. doi: 10.1007/s11095-019-2678-4.

Abstract

PURPOSE

Pancreatic Polypeptide-secreting tumor of the distal pancreas (PPoma) is a rare, difficult and indolent type of cancer with a survival rate of 5-year in only 10% of all cases. The PPoma is classified as a neuroendocrine tumor (NET) not functioning that overexpresses SSTR 2 (somatostatin receptor subtype 2). Thus, in order to improve the diagnosis of this type of tumor, we developed nanoparticulate drug carriers based on poly-lactic acid (PLA) polymer loaded with octreotide and radiolabeled with Technetium-99 m (Tc).

METHODS

PLA/PVA octreotide nanoparticles were developed by double-emulsion technique. These nanoparticles were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) and radiolabeled with 99mTc by the direct via forming Tc-PLA/PVA octreotide nanoparticles. The safety of these nanosystems was evaluated by the MTT cell toxicity assay and their in vivo biodistribution was evaluated in xenografted inducted animals.

RESULTS

The results showed that a 189 nm sized nanoparticle were formed with a PDI of 0,097, corroborating the monodispersive behavior. These nanoparticles were successfully radiolabeled with 99mTc showing uptake by the inducted tumor. The MTT assay corroborated the safety of the nanosystem for the cells.

CONCLUSION

The results support the use of this nanosystem (Tc-PLA/PVA octreotide nanoparticles) as imaging agent for PPoma. Graphical Abstract Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma) Radiolabeled Nanoparticles for Imaging.

摘要

目的

胰腺远端多肽分泌肿瘤(PPoma)是一种罕见、难以治疗且进展缓慢的癌症,所有病例的 5 年生存率仅为 10%。PPoma 被归类为过度表达 SSTR2(生长抑素受体亚型 2)的无功能神经内分泌肿瘤(NET)。因此,为了提高这种肿瘤的诊断水平,我们开发了基于聚乳酸(PLA)聚合物的载有奥曲肽的纳米药物载体,并进行了锝-99m(Tc)放射性标记。

方法

通过双重乳液技术开发 PLA/PVA 奥曲肽纳米粒。通过原子力显微镜(AFM)和动态光散射(DLS)对这些纳米粒进行了表征,并通过直接形成 Tc-PLA/PVA 奥曲肽纳米粒对其进行了 99mTc 放射性标记。通过 MTT 细胞毒性测定评估了这些纳米系统的安全性,并在异种移植诱导的动物中评估了其体内生物分布。

结果

结果表明,形成了粒径为 189nm、PDI 为 0.097 的纳米粒,表明其具有单分散性。这些纳米粒成功地被 99mTc 放射性标记,显示出对诱导肿瘤的摄取。MTT 测定证实了纳米系统对细胞的安全性。

结论

这些结果支持使用这种纳米系统(Tc-PLA/PVA 奥曲肽纳米粒)作为 PPoma 的成像剂。

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