Efficacy of bio-targeted drug-loaded nanoparticles on diagnosis and treatment for breast cancer based on hypoxic environment

• Main Authors: WANG Lu, JIANG Fujie, YANG Haiyan, WANG Disen, WANG Yaotai, TANG Yu, WANG Qi, ZOU Jianzhong
• Format: Article
• Language: zho
• Published: Editorial Office of Journal of Third Military Medical University 2021-05-01
• Series: Di-san junyi daxue xuebao
• Subjects: hypoxia; bifidobacterium; hypoxia-activated prodrugs; high-intensity focused ultrasound; tumor
• Online Access: http://aammt.tmmu.edu.cn/Upload/rhtml/202012046.htm

Objective To investigate the efficacy of bio-targeted drug loaded nanoparticles for the diagnosis and treatment of breast cancer based on tumor hypoxia microenvironment. Methods Lipid nanoparticles loaded with perfluorohexane (PFH) and tirazamine (TPZ) were prepared by film hydration. Bifidobacteria were cultured and detected for basic characterizations. Then, the bacteria and nanoparticles were connected by electrostatic adsorption to prepare bio-targeted drug-loaded nanoparticles, and laser confocal microscopy and flow cytometry were used to detect the binding between them. Ultrasonic diagnostic imaging, MTT assay and flow cytometry were adopted to observe the in vitro imaging performance and killing effect on breast cancer cells after high-intensity focused ultrasound (HIFU) irradiation. Tissue homogenate was used to observe the targeting ability of bifidobacteria. In vivo fluorescence imaging was performed to monitor the targeting of nanoparticles. The 4T1 breast tumor-bearing mice were established and randomly divided into targeted group (n=3) and non-targeted group (n=3) to observe the ultrasound imaging performance of nanoparticles. The tumor-bearing mice were randomly divided into blank control group, PBS+HIFU group, nonoparticles+HIFU group, and nonoparticles+ bifidobacterium+HIFU group (n=3 for each group). The body weight and tumor volume were recorded during treatment process, HE staining was performed 14 d later to observe the morphological changes of the tumor mass. Results Bio-targeted drug loaded nanoparticles were successfully prepared. The nanoparticles had an average size of 218.93±6.56 nm and a zeta potential of 55.00±4.97 mV, and the bifidobacterium had a potential of -28.10±7.52 mV. The connection rate of the nanoparticles and bacterium was (99.04±0.40)%. The nanoparticles showed better ultrasound imaging after HIFU irradiation. The results of MTT assay and flow cytometry showed that the nanoparticles exerted better killing effect on breast cancer cells under hypoxic condition than under normoxia condition (P < 0.05). The results of tissue homogenate demonstrated that bifidobacteria showed good target ability. In vivo fluorescence imaging displayed that the nanoparticles were enriched around the tumor. In vivo ultrasound imaging was achieved in the targeted group after HIFU irradiation. Both the records of tumor volume and results of HE staining indicated that the nonoparticles+bifidobacterium+HIFU group got the best tumor inhibitory effect (P < 0.05). Conclusion The bio-targeted drug loaded nanoparticles can effectively diagnose and treat breast cancer based on hypoxia microenvironment. Our study provides a new thought for the integration of tumor diagnosis and treatment.