| Objective:To compare the anti-tumor efficacy of recombinant Abraxane(?)/anti-HER2 antibody complex(Abra/anti-HER2)with Abraxane(?)and Taxol(?)on the proliferation and apoptosis of breast cancer cell lines SKBR-3 in vitro and in vivo and discuss the possible mechanism.Methods:Abra/anti-HER2 was synthesized using EDC/NHS by surface activation method,morphological characteristics of the Abra/anti-HER2 nanocomposites were examined using TEM,and DLS was performed to determine the hydrodynamic radius(Rh)of the Abra/anti-HER2.The proliferation inhibition effect was determined using CCK-8 assay.Apoptosis was analyzed by DAPI staining.Cell cycle distributions were detected by flow cytometry.The expression of apoptosis-related protein was detected by Western blot analysis.In vivo anti-tumor efficacy,in vivo NIRF imaging and biodistribution study of NIR-797-labeled drugs were carried in tumor-bearing mice.Results:Abra/anti-HER2 was fabricated by a "one-step" synthesis using EDC/NHS.In vitro analysis of cell viability and cell cycle revealed that Abra/anti-HER2 showed more cytotoxicity against HER2(+)SKBR-3 cells than Abraxane(?)at equivalent PTX concentration.In addition,in HER2(+)breast cancer xenograft model,Abra/anti-HER2 significantly inhibited tumor growth with less side effects.Moreover,the properties of more precise target and delayed release of PTX were proved by NIRF imaging.Thus,our results indicate that Abra/anti-HER2 could represent a next-generation sequentially dual-target therapeutic agent for HER2(+)breast cancer.Conclusion:In summary,our research successfully synthesised a sequentially dual-targeting recombinant Abra/anti-HER2 for the treatment of HER2(+)breast cancer.In vivo and in vitro experiments demonstrate that Abra/anti-HER2 outperforms Abraxane(?),the current gold standard for PTX delivery with the properties of sequentially dual-targeting and more cytotoxicity to HER2(+)breast cancer.Our study may open up a new idea in such a dilemma for the treatment of breast cancer. |
PDF Full Text Request