PSMA-Targeted Theranostic Nanocarrier for Prostate Cancer.-猫眼课题宝

DOI：

10.7150/thno.18879

发表时间：

2017

期刊：

Theranostics

影响因子：

12.4

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

Flores O;Santra S;Kaittanis C;Bassiouni R;Khaled AS;Khaled AR;Grimm J;Perez JM

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525751/

在此，我们报告了使用治疗诊断纳米载体（叶酸-HBPE（CT 20 p））将治疗肽递送至表达PSMA（叶酸水解酶1）的前列腺癌肿瘤。治疗肽（CT 20 p）靶向并抑制含有伴侣蛋白的TCP-1（CCT）蛋白折叠复合物，对癌细胞具有选择性细胞毒性，并且对正常组织无毒。通过PSMA将CT 20 p递送至前列腺癌细胞，实现了双重水平的癌症特异性：（1）选择性靶向表达PSMA的前列腺肿瘤，和（2）对癌细胞的特异性细胞毒性，对正常细胞的毒性最小。当使用近红外染料作为货物时，PSMA靶向治疗诊断纳米载体可以对PSMA表达细胞和肿瘤进行成像。同时，当治疗剂如CT 20 p肽被封装在纳米载体内时，它可用于治疗表达PSMA的肿瘤。即使当这些靶向PSMA的纳米载体被巨噬细胞吸收时，在这些细胞中也观察到最小的细胞死亡，这与导致显著巨噬细胞死亡的基于阿霉素的治疗剂形成对比。将表达PSMA的前列腺癌细胞与叶酸-HBPE（CT 20 p）纳米载体一起孵育，诱导细胞形态发生显著变化，整合素β1水平降低，细胞粘附力降低，最终导致细胞死亡。这些结果是相关的，因为整合素β1在前列腺癌侵袭和转移潜力中起关键作用。此外，使用开发的PSMA靶向纳米载体有助于将CT 20 p选择性地体内递送至PSMA阳性肿瘤，从而诱导肿瘤大小的显著减小。

Herein, we report the use of a theranostic nanocarrier (Folate-HBPE(CT20p)) to deliver a therapeutic peptide to prostate cancer tumors that express PSMA (folate hydrolase 1). The therapeutic peptide (CT20p) targets and inhibits the chaperonin-containing TCP-1 (CCT) protein-folding complex, is selectively cytotoxic to cancer cells, and is non-toxic to normal tissue. With the delivery of CT20p to prostate cancer cells via PSMA, a dual level of cancer specificity is achieved: (1) selective targeting to PSMA-expressing prostate tumors, and (2) specific cytotoxicity to cancer cells with minimal toxicity to normal cells. The PSMA-targeting theranostic nanocarrier can image PSMA-expressing cells and tumors when a near infrared dye is used as cargo. Meanwhile, it can be used to treat PSMA-expressing tumors when a therapeutic, such as the CT20p peptide, is encapsulated within the nanocarrier. Even when these PSMA-targeting nanocarriers are taken up by macrophages, minimal cell death is observed in these cells, in contrast with doxorubicin-based therapeutics that result in significant macrophage death. Incubation of PSMA-expressing prostate cancer cells with the Folate-HBPE(CT20p) nanocarriers induces considerable changes in cell morphology, reduction in the levels of integrin β1, and lower cell adhesion, eventually resulting in cell death. These results are relevant as integrin β1 plays a key role in prostate cancer invasion and metastatic potential. In addition, the use of the developed PSMA-targeting nanocarrier facilitates the selective in vivo delivery of CT20p to PSMA-positive tumor, inducing significant reduction in tumor size.