iRGD-Guided Silica/Gold Nanoparticles for Efficient Tumor-Targeting and Enhancing Antitumor Efficacy Against Breast Cancer

Xuefeng Hou,1– 4,* Qi Chen,1,* Ying Fang,5 Li Zhang,1 Shuoheng Huang,1 Minjie Xu,1 Yaning Ren,1 Zhansen Shi,1 Yan Wei,1 Lihua Li1– 4 1School of Pharmacy, Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 2Anhui Provincial Engineering Laboratory for Screening and Re-Evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 3Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 4Drug Research and Development Center, Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 5School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Wei; Lihua Li, School of Pharmacy, Wannan Medical College, No. 22, West Wenchang Road, Wuhu, 241002, People’s Republic of China, Email yanwei@wnmc.edu.cn; llh05530226@126.comBackground: Breast cancer presents significant challenges due to the limited effectiveness of available treatments and the high likelihood of recurrence. iRGD possesses both RGD sequence and C-terminal sequence and has dual functions of targeting and membrane penetration. iRGD-modified nanocarriers can enhance drug targeting of tumor vascular endothelial cells and penetration of new microvessels, increasing drug concentration in tumor tissues.Methods: The amidation reaction was carried out between SiO2/AuNCs and iRGD/PTX, yielding a conjugated drug delivery system (SiO2/AuNCs-iRGD/PTX, SAIP@NPs). The assessment encompassed the characterization of the morphology, particle size distribution, physicochemical properties, in vitro release profile, cytotoxicity, and cellular uptake of SAIP@NPs. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed using a small animal in vivo imaging system and a tumor-bearing nude mice model, respectively. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed utilizing a small animal in vivo imaging system and an in situ nude mice breast cancer xenograft model, respectively.Results: The prepared SAIP@NPs exhibited decent stability and a certain slow-release effect in phosphate buffer (PBS, pH 7.4). In vitro studies had shown that, due to the dual functions of transmembrane and targeting of iRGD peptide, SAIP@NPs exhibited strong binding to integrin αvβ 3, which was highly expressed on the membrane of MDA-MB-231 cells, improving the uptake capacity of tumor cells, inhibiting the rapid growth of tumor cells, and promoting tumor cell apoptosis. The results of animal experiments further proved that SAIP@NPs had longer residence time in tumor sites, stronger anti-tumor effect, and no obvious toxicity to major organs of experimental animals.Conclusion: The engineered SAIP@NPs exhibited superior functionalities including efficient membrane permeability, precise tumor targeting, and imaging, thereby significantly augmenting the therapeutic efficacy against breast cancer with a favorable safety profile. Keywords: silicon dioxide nanoparticles, gold nanoclusters, iRGD penetrating peptide, integrin αvβ 3, tumor targeting, breast cancer