Affiliation:
1. National Glycoengineering Research Center Shandong University Qingdao Shandong 266237 China
2. NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate‐Based Medicine Shandong University Qingdao 266237 China
3. Shandong Provincial Technology Innovation Center of Carbohydrate Shandong University Qingdao 266237 China
4. School of Pharmaceutical sciences Shandong University Jinan 250012 China
Abstract
AbstractThe progression and metastasis of solid tumors rely strongly on neovascularization. However, angiogenesis inhibitors alone cannot meet the needs of tumor therapy. This study prepared a new drug conjugate (PTX‐GSHP‐CYS‐ES2, PGCE) by combining polysaccharides (heparin without anticoagulant activity, GSHP), chemotherapeutic drugs (paclitaxel, PTX), and antiangiogenic drugs (ES2). Furthermore, a tumor‐targeted prodrug nanoparticle delivery system is established. The nanoparticles appear to accumulate in the mitochondrial of tumor cells and achieve ES2 and PTX release under high glutathione and acidic environment. It has been confirmed that PGCE inhibited the expression of multiple metastasis‐related proteins by targeting the tumor cell mitochondrial apparatus and disrupting their structure. Furthermore, PGCE nanoparticles inhibit migration, invasion, and angiogenesis in B16F10 tumor‐bearing mice and suppress tumor growth and metastasis in vitro. Further in vitro and in vivo experiments show that PGCE has strong antitumor growth and metastatic effects and exhibits efficient anti‐angiogenesis properties. This multi‐targeted nanoparticle system potentially enhances the antitumor and anti‐metastatic effects of combination chemotherapy and antiangiogenic drugs.
Funder
Natural Science Foundation of Shandong Province
Key Technology Research and Development Program of Shandong
Subject
Biomaterials,Biotechnology,General Materials Science,General Chemistry
Cited by
6 articles.
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