CD44-Specific A6 Short Peptide Boosts Targetability and Anticancer Efficacy of Polymersomal Epirubicin to Orthotopic Human Multiple Myeloma
Wenxing Gu1, 2, Jingnan An3, Hao Meng1, Na Yu1, Yinan Zhong1, Fenghua Meng*,1(孟凤华), Yang Xu*,3(徐扬), Jeroen J. L. M. Cornelissen2, and Zhiyuan Zhong*,1(钟志远)
1Biomedical Polymers Laboratory College of Chemistry Chemical Engineering and Materials Science State Key Laboratory of Radiation Medicine and Protection Soochow University Suzhou 215123, P. R. China
2Department of Biomolecular Nanotechnology MESA+ Institute for Nanotechnology University of Twente 7500 AE Enschede, The Netherlands
3Jiangsu Institute of Hematology The First Affiliated Hospital of Soochow University Institute of Blood and Marrow Transplantation of Soochow University Collaborative Innovation Center of Hematology Soochow University Suzhou 215123, P. R. China
ADVANCED MATERIALS
Chemotherapy is widely used in the clinic though its benefits are controversial owing to low cancer specificity. Nanovehicles capable of selectively transporting drugs to cancer cells have been energetically pursued to remodel cancer treatment. However, no active targeting nanomedicines have succeeded in clinical translation to date, partly due to either modest targetability or complex fabrication. CD44-specific A6 short peptide (KPSSPPEE) functionalized polymersomal epirubicin (A6-PS-EPI), which boosts targetability and anticancer efficacy toward human multiple myeloma (MM) in vivo, is described. A6-PS-EPI encapsulating 11 wt% EPI is small (≈55 nm), robust, reduction-responsive, and easy to fabricate. Of note, A6 decoration markedly augments the uptake and anticancer activity of PS-EPI in CD44- overexpressing LP-1 MM cells. A6-PS-EPI displays remarkable targeting ability to orthotopic LP-1 MM, causing depleted bone damage and striking survival benefits compared to nontargeted PS-EPI. Overall, A6-PS-EPI, as a simple and intelligent nanotherapeutic, demonstrates high potential for clinical translation.
链接:https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.201904742