Chondroitin Sulfate Targeting Nanodrug Achieves Near-Infrared Fluorescence-Guided Chemotherapy Against Triple-Negative Breast Primary and Lung Metastatic Cancer

Abstract

Chen Huang,1,* Chunbin Li,2,3,* Jiaxuan Cai,1,4,* Jie Chen,1 Baobei Wang,1 Mengxia Li,1 Wei Zhou,5 Jianguo Wang,3 Pengfei Zhang,2 Jian V Zhang1 1Center for Energy Metabolism and Reproduction, Shenzhen Key Laboratory of Metabolic Health, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 2Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Bioactive Materials Engineering Laboratory for Medicine, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 3College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, People’s Republic of China; 4Shenzhen College of Advanced Technology, University of Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 5Gynecology Department, Huazhong University of Science and Technology Union, Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian V Zhang; Pengfei Zhang, Shenzhen Institute of Advance Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]; [email protected]: Lack of highly expressed tumor target and ligands limits application of nano-medicine against triple-negative breast cancer (TNBC). Previous study reported that placenta-derived oncofetal chondroitin sulfate glycosaminoglycan chain (CSA) expressed on 90% of stage I–III invasive ductal breast carcinomas. Our study found the CSA anchor protein VAR2CSA derived small peptide plCSA had strong binding activity with TNBC cell lines and tumor tissue. Here, we combined the AIEgens TBZ-DPNA and therapy drug paclitaxel (PTX) to fabricate near-infrared fluorescence-guided nanodrug (plCSA-NP) to investigate its targeting and anti-tumor effect on TNBC.Methods: We synthesized and purified TBZ-DPNA with one step, measured optical properties and photoluminescence (PL) spectra. We prepared nanodrug plCSA-NP by encapsulating TBZ-DPNA and PTX and conjugating them with peptide plCSA. We evaluated plCSA-NP targeting activity by examining AIEdots fluorescence signal on TNBC cell lines and subcutaneous and lung metastatic mouse model. We assessed PTX delivery effect by cytotoxicity assay on TNBC line and tumor growth of subcutaneous and lung metastatic mouse models.Results: PL spectra and TEM imaging results showed plCSA-NP had maximum emission feature at 718 nm and nearly monodispersed nanosphere with an average diameter of 70 nm. In vitro studies showed plCSA-NPs had high affinity and cytotoxicity with TNBC cell lines. In vivo subcutaneous and lung metastasis mouse studies showed plCSA-NPs accumulated on TNBC tumor tissue, and significantly prevented TNBC subcutaneous and lung metastasis tumor growth.Conclusion: In conclusion, we provide solid evidence for chondroitin sulfate targeting peptide plCSA guided nanodrug, exhibit good targeting efficiency and therapeutic effect against TNBC primary and lung metastatic tumor growth.Keywords: triple-negative breast cancer, lung metastasis, chemotherapy, aggregation-induced emission, drug delivery system, plCSA

Keywords

• triple negative breast cancer
• lung metastasis
• chemotherapy
• aggregation-induced emission
• drug delivery system
• plcsa