Biomedical 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.
Department of Biomolecular Nanotechnology, MESA+ Institute for Nanotechnology, University of Twente, 7500 AE, Enschede, The Netherlands.
Adv Mater. 2019 Nov;31(46):e1904742. doi: 10.1002/adma.201904742. Epub 2019 Sep 27.
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.
化疗在临床上被广泛应用，但其益处因癌症特异性低而存在争议。人们积极寻求能够选择性地将药物输送到癌细胞的纳米载体，以重塑癌症治疗方法。然而，到目前为止，还没有任何主动靶向的纳米药物成功转化为临床应用，部分原因是靶向性或复杂的制造工艺不够。本文描述了一种 CD44 特异性 A6 短肽（KPSSPPEE）功能化聚合物体阿霉素（A6-PS-EPI），它可以提高体内人多发性骨髓瘤（MM）的靶向性和抗癌疗效。A6-PS-EPI 包封了 11wt%的 EPI，具有尺寸小（≈55nm）、稳定性好、还原响应性强和易于制备等特点。值得注意的是，A6 修饰显著增加了 PS-EPI 在 CD44 过表达的 LP-1 MM 细胞中的摄取和抗癌活性。A6-PS-EPI 对原位 LP-1 MM 具有显著的靶向能力，与非靶向 PS-EPI 相比，它能减轻骨损伤，显著提高存活率。总的来说，A6-PS-EPI 作为一种简单而智能的纳米治疗药物，具有很高的临床转化潜力。
