Membrane cholesterol enrichment and folic acid functionalization lead to increased accumulation of erythrocyte-derived optical nano-constructs within the ovarian intraperitoneal tumor implants in mice
Membrane cholesterol enrichment and folic acid functionalization lead to increased accumulation of erythrocyte-derived optical nano-constructs within the ovarian intraperitoneal tumor implants in mice
复制标题
DOI：
10.1016/j.nano.2023.102728
复制
发表时间：
2023-12-11
影响因子：
5.4
通讯作者：
Anvari，Bahman
中科院分区：
文献类型：
--
作者：
Lee，Chi-Hua;Mac，Jenny;Anvari，Bahman
细胞减灭术仍然是治疗卵巢癌的金标准，但疗效有限，因为并非所有肿瘤都可以在术中可视化切除。我们设计了红细胞衍生的纳米结构，封装了近红外（NIR）荧光团吲哚菁绿（ICG），作为卵巢肿瘤近红外荧光成像的光学探针。在这里，我们用胆固醇丰富了这些纳米结构的膜，并用叶酸（FA）功能化其表面以靶向叶酸受体-α。使用小鼠模型，我们表明，在注射后 24 小时，具有膜胆固醇富集和 FA 功能化的纳米结构的每个肿瘤质量的平均注射剂量比非封装 ICG 高约六倍，比仅富含胆固醇的纳米结构高约两倍，比仅具有 FA 功能化的纳米结构高 33%。这些结果表明，含有胆固醇和 FA 的红细胞衍生纳米结构为改善卵巢肿瘤荧光成像提供了一个平台。
Cytoreductive surgery remains as the gold standard to treat ovarian cancer, but with limited efficacy since not all tumors can be intraoperatively visualized for resection. We have engineered erythrocyte-derived nano-constructs that encapsulate the near infrared (NIR) fluorophore, indocyanine green (ICG), as optical probes for NIR fluorescence imaging of ovarian tumors. Herein, we have enriched the membrane of these nano-constructs with cholesterol, and functionalized their surface with folic acid (FA) to target the folate receptor-α. Using a mouse model, we show that the average fraction of the injected dose per tumor mass for nano-constructs with both membrane cholesterol enrichment and FA functionalization was ~ sixfold higher than non-encapsulated ICG, ~ twofold higher than nano-constructs enriched with cholesterol alone, and 33 % higher than nano-constructs with only FA functionalization at 24-h post-injection. These results suggest that erythrocyte-derived nano-constructs containing both cholesterol and FA present a platform for improved fluorescence imaging of ovarian tumors.