Department of Biomedical Engineering, National University of Singapore, Kent Ridge 117583, Singapore.
Department of Surgery, National University of Singapore, Kent Ridge 119228, Singapore.
Nanomedicine. 2022 Nov;46:102600. doi: 10.1016/j.nano.2022.102600. Epub 2022 Sep 5.
Current intravesical chemotherapy for non-muscle invasive bladder cancer (NMIBC) has limited efficacy due to loss of the instilled agent from urine voiding and the agent's lack of specificity for the tumors. We developed a nanocarrier (txCD47-HNP, ∼100 nm) based on human serum albumin conjugated with a peptide that targets the cluster of differentiation 47 receptor overexpressed on bladder cancer (BC) cells. The IC of gemcitabine elaidate (GEM) loaded in the txCD47-HNP was almost an order of magnitude lower than that of free GEM. In a mouse orthotopic BC model, GEM loaded in txCD47-HNP effectively reduced the tumor burden. Tumor cells in BC patients' urine can also be targeted by fluorescence-labeled txCD47-HNP resulting in >83 % of the cells exhibiting fluorescence. Thus, txCD47-HNP can potentially be a theranostic agent in NMIBC management by serving as a targeted drug delivery vehicle as well as an alternative to urine cytology.
由于尿液排空导致灌注药物损失以及药物缺乏对肿瘤的特异性,目前用于非肌肉浸润性膀胱癌(NMIBC)的膀胱内化疗疗效有限。我们开发了一种基于人血清白蛋白的纳米载体(txCD47-HNP,约 100nm),该载体与一种肽连接,该肽靶向在膀胱癌(BC)细胞上过表达的分化群 47 受体。负载在 txCD47-HNP 中的吉西他滨油酸酯(GEM)的 IC 比游离 GEM 低一个数量级。在小鼠原位 BC 模型中,负载在 txCD47-HNP 中的 GEM 可有效降低肿瘤负担。BC 患者尿液中的肿瘤细胞也可以被荧光标记的 txCD47-HNP 靶向,导致超过 83%的细胞显示荧光。因此,txCD47-HNP 可以作为一种治疗药物,通过作为靶向药物递送载体以及替代尿液细胞学,在 NMIBC 管理中具有潜在的应用。