Affiliation:
1. State Key Laboratory of Microbial Technology Shandong University Qingdao 266237 China
2. China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry College of Biotechnology Tianjin University of Science & Technology Tianjin 300457 China
3. Jinan Zhensheng School Jinan 250102 China
4. Jinan Food and Drug Inspection and Testing Center Jinan 250101 China
Abstract
AbstractBy conjugating a chemotherapeutic candidate drug 4β‐NH‐(5‐aminoindazole)‐podophyllotoxin (βIZP) and an immunosuppressive protein galectin‐1 targeted aptamer AP74, a chemo‐immunotherapy molecule (AP74‐βIZP) is developed against liver cancer. AP74‐βIZP can target galectin‐1 and enrich the tumor microenvironment to improve the tumor inhibition ratio by 6.3%, higher than that of βIZP in a HepG2 xenograft model. In safety evaluation, βIZP cannot be released from AP74‐βIZP in normal tissues with low glutathione level. Therefore, the degrees of organs injury and myelosuppression after the treatment with AP74‐βIZP are lower than those with βIZP. After 21 d treatment at a drug dose of 5 mg kg−1, AP74‐βIZP does not cause weight loss in mice, while the weight is significantly reduced by 24% and 14% from oxaliplatin and βIZP, respectively. In immune synergy, AP74‐IZP enhances CD4/CD8 cell infiltration to promote the expression of cell factor (i.e., IL‐2, TNF‐α, and IFN‐γ), which further improves the antitumor activity. The tumor inhibition ratio of AP74‐βIZP is 70.2%, which is higher than that of AP74 (35.2%) and βIZP (48.8%). Because of the dual effects of chemotherapy and immunotherapy, AP74‐βIZP exhibits superior activity and lower toxicity. The approach developed in this work could be applicable to other chemotherapy drugs.
Funder
National Natural Science Foundation of China
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials
Cited by
2 articles.
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