RGD Peptide and PAD4 Inhibitor-Loaded Gold Nanorods for Chemo-Photothermal Combined Therapy to Inhibit Tumor Growth, Prevent Lung Metastasis and Improve Biosafety

RGD肽和PAD4抑制剂负载金纳米棒用于化学光热联合治疗以抑制肿瘤生长、预防肺转移和提高生物安全性

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作者:Yu Lu, Zidong Peng, Di Zhu, Yijiang Jia, Ayijiang Taledaohan, Yuanming Li, Jiawang Liu, Yanming Wang, Yuji Wang

Conclusion

Thus, an RGD targeting and PAD4 inhibitor-loaded system are established based on chemo-photothermal combined therapy. It could inhibit tumor growth, prevent lung metastasis and improve biosafety.

Methods

In vitro cytotoxicity test and in vivo S180 tumor-bearing mice model were used to compare antitumor activity of 356-modified gold nanospheres and nanorods. The A549 tumor-bearing mice model was also exploited in antitumor assessment. In addition, ICP-MS, blood cell analyzer and blood biochemistry analyzer are applied for assessing the biosafety of NPs.

Purpose

A targeted drug delivery system that combines protein-arginine deiminase type-4 (PAD4) inhibitors YW3-56 (356) with PTT of NPs is constructed to both decrease the accumulation of gold in metabolic organs and reduce the dose of chemotherapeutic agents. Patients and

Results

Both 356-modified gold nanospheres and nanorods showed antitumor activity. However, 356-loaded gold nanorods are found to have better tumor inhibitory activity than 356-loaded gold nanospheres in the presence of laser and without laser irradiation. Thus, 356-loaded gold nanorods are selected to be applied for chemo-photothermal combined therapy on in vivo. We find that combination therapy could inhibit tumor growth and reduce lung tumor metastasis and inflammatory infiltration compared with individual therapy. It triggers apoptosis in tumor tissue observed by TUNEL assay and TEM pictures.

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