Selective Cell Penetrating Peptide‐Functionalized Polymersomes Mediate Efficient and Targeted Delivery of Methotrexate Disodium to Human Lung Cancer In Vivo
Weijing Yang , Yifeng Xia ,Yuan Fang ,Fenghua Meng*（孟凤华）,Jian Zhang ,Ru Cheng ,Chao Deng ,Zhiyuan Zhong*（钟志远）
Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, P. R. China
Advanced healthcare materials,2018,7(7),1701135
It is a long challenge to develop nanomedicines that simultaneously possess tumor cell selectivity and penetration functions. Here, it is reported that selective cell penetrating peptide (RLWMRWYSPRTRAYGC)‐functionalized polymersomes (SCPP‐PS) mediate efficient and targeted delivery of methotrexate disodium (MTX) to human lung cancer in vivo. SCPP‐PS with an SCPP density of 18.7% is self‐crosslinked, has a small size (63–65 nm), and high MTX loading (up to 19.4 wt%), shows selective uptake and fast penetration into A549 lung cancer cells, and efficiently releases MTX intracellularly. Interestingly, MTX‐loaded SCPP‐PS (MTX‐SCPP‐PS) displays much lower IC50than those of MTX‐PS and free MTX. Installing SCPP to polymersomes has no detrimental effect to their long blood circulation time but significantly increases drug accumulation in A549 tumor (5.3% injected dose per gram at 8 h post injection). Remarkably, SCPP‐PS exhibits deep penetration in to A549 tumors. MTX‐SCPP‐PS completely inhibits tumor progression and significantly improves survival rates in mice bearing A549 lung tumor xenografts as compared to MTX‐PS and free MTX groups (median survival time: 75 vs 45 and 38 d, respectively), without causing noticeable adverse effects. These results highlight that functionalization of nanomedicines with SCPP is a feasible strategy to achieve efficient and targeted tumor therapy.
链接：https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.201701135