研究亮点

研究亮点
当前位置:首页 > 研究亮点 > 研究亮点
Adv. Mater. 2016, 28, 8234-8239.

Here, we report on a novel anisamide-functionalized reversibly cross-linked chimeric polymersome (Anis-RCCP) that shows effi cient loading and in vivo lung tumor-targeting delivery of a water soluble clinical anticancer drug, methotrexate sodium (MTX⋅2Na), resulting in complete tumor growth inhibition, 100% survival rate, and depleted adverse effects. MTX⋅2Na (Trexall) is prescribed and usedfor the treatment of rheumatoid arthritis, severe psoriasis, and various types of cancers including breast, leukemia, lymphoma, lung, and osteosarcoma. MTX⋅2Na takes effects by prohibiting the metabolism of folic acid via competitively inhibiting dihydrofolate reductase, an enzyme participating in the tetrahydrofolate synthesis. MTX⋅2Na suffers, nevertheless, a poor pharmacokinetics and narrow therapeutic window, which significantly limits its therapeutic outcomes. In the past years, different delivery approaches such as MTX-polymer conjugates and MTX-encapsulated liposomes, micelles, and nanoparticles have been explored to reduce its dose-limiting side effects and increase therapeutic effi cacy. However, none of these systems have advanced to the clinical settings due to problems of complex fabrication, low drug loading, fast drug leakage, or poor tumor selectivity. Here, Anis-RCCP was formed from poly(ethylene glycol)- b -poly(N-2-hydroxypropyl methacrylamideg-lipoic acid)- b -poly(2-(dimethylamino)ethyl methacrylate) (PEG-P(HPMA-LA)-PDMA) and Anis-PEG-P(HPMA-LA)-PDMA asymmetric triblock copolymers, in which PEG was longer than PDMA. The presence of positively charged PDMA in the watery core would allow effi cient loading of MTX⋅2Na. The vesicular membrane is made of P(HPMA-LA), which can be readily cross-linked in the presence of catalytic dithiothreitol (DTT) to stabilize polymersomes and prevent drug leakage. Under cytoplasmic reductive conditions, nevertheless, the polymersomes would be automatically decrosslinked, leading to fast intracellular drug release. PHPMA is a biocompatible and water soluble polymer widely investigated for drug delivery. LA is a natural antioxidant produced by the human body and used to treat diabetic neuropathy. The decoration of polymersome surface with anisamide would impart high affi nity and targetability to sigma receptors that are overexpressed on many human malignancies including lung cancers. Lung cancer has become a leading cause of death worldwide.

Efficient and targeted suppression of human lung tumor xenografts in mice with methotrexate sodium encapsulated in all-function-in-one chimaeric polymersomes. (Adv. Mater. 2016, 28, 8234-8239)

返回