(cRGD)2 peptides modified nanoparticles increase tumor-targeting therapeutic effects by co-delivery of albendazole and iodine-131

xlomafota13 shared this article with you from Inoreader (cRGD)2 peptides modified nanoparticles increase tumor-targeting therapeutic effects by co-delivery of albendazole and iodine-131 Via radioactive iodine Anticancer Drugs. 2021 Jul 12. doi: 10.1097/CAD.0000000000001135. Online ahead of print. ABSTRACT BACKGROUND: Albendazole (ABZ), a clinical antiparasitic drug, has shown potential antitumor effects in various tumors. Herein, we prepared dimeric cRGD [(cRGD)2] modified human serum albumin (HSA) nanosystem to co-delivery of albendazole (ABZ) and iodine-131 (131I) for chemoradiotherapy of triple-negative breast cancer (TNBC). MATERIALS METHODS: HSA@ABZ NPs were synthesized by th e self-assembly method. 131I-(cRGD)2/HSA@ABZ NPs were fabricated through covalently binding HSA@ABZ NPs with (cRGD)2 peptides, followed by chloramine T direct labeling with 131I. In vitro therapeutic effects on TNBC (MDA-MB-231 and 4T1 cells) were determined using MTT assay, crystal violet assay, wound-healing assay and western blotting analysis. In vivo treatment was performed using 4T1-bearing mice, and the tumor-targeting efficacy was assessed by gamma imaging. The distribution of NPs was quantitatively analyzed by detecting the gamma counts in tumor and main organs. RESULTS: The nanoparticles possessed negative charge, moderate size and good polydispersity index. Dual responding to pH and redox, the in vitro release rate of ABZ was more than 80% in 72 h. In vitro, NPs inhibited the proliferation of TNBC cells in a concentration-dependent manner and decreased cell migration. Western blotting analysis showed that the NPs, as well as free ABZ, cell-dependently induced autopha gy and apoptosis by restraining or promoting the expression of p-p38 and p-JNK MAPK. In vivo, gamma imaging exhibited an earlier and denser radioactivity accumulation in tumor of 131I-(cRGD)2/HSA@ABZ NPs compared to NPs free of (cRGD)2 conjugating. Furthermore, 131I-(cRGD)2/HSA@ABZ NPs significantly suppressed tumor growth by restraining proliferation and promoting apoptosis in vivo. CONCLUSIONS: Our study suggested that the nanoparticles we developed enhanced tumor-targeting of ABZ and increased antitumor effects by combination of chemotherapy and radiotherapy. PMID:34261920 | DOI:10.1097/CAD.000000000000113 5 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.