Department of Pharmaceutics, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.
Institute of Materia Medica, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.
Nano Lett. 2017 Feb 8;17(2):1056-1064. doi: 10.1021/acs.nanolett.6b04523. Epub 2017 Jan 17.
Targeting of nanoparticles to distant diseased sites after oral delivery remains highly challenging due to the existence of many biological barriers in the gastrointestinal tract. Here we report targeted oral delivery of diverse nanoparticles in multiple disease models, via a "Trojan horse" strategy based on a bioinspired yeast capsule (YC). Diverse charged nanoprobes including quantum dots (QDs), iron oxide nanoparticles (IONPs), and assembled organic fluorescent nanoparticles can be effectively loaded into YC through electrostatic force-driven spontaneous deposition, resulting in different diagnostic YC assemblies. Also, different positive nanotherapies containing an anti-inflammatory drug indomethacin (IND) or an antitumor drug paclitaxel (PTX) are efficiently packaged into YC. YCs containing either nanoprobes or nanotherapies may be rapidly endocytosed by macrophages and maintained in cells for a relatively long period of time. Post oral administration, nanoparticles packaged in YC are first transcytosed by M cells and sequentially endocytosed by macrophages, then transported to neighboring lymphoid tissues, and finally delivered to remote diseased sites of inflammation or tumor in mice or rats, all through the natural route of macrophage activation, recruitment, and deployment. For the examined acute inflammation model, the targeting efficiency of YC-delivered QDs or IONPs is even higher than that of control nanoprobes administered at the same dose via intravenous injection. Assembled IND or PTX nanotherapies orally delivered via YCs exhibit remarkably potentiated efficacies as compared to nanotherapies alone in animal models of inflammation and tumor, which is consistent with the targeting effect and enhanced accumulation of drug molecules at diseased sites. Consequently, through the intricate transportation route, nanoprobes or nanotherapies enveloped in YC can be preferentially delivered to desired targets, affording remarkably improved efficacies for the treatment of multiple diseases associated with inflammation.
由于胃肠道中存在许多生物屏障，因此，经口服给药将纳米颗粒靶向递送至远处病变部位仍然极具挑战性。在此，我们报告了通过基于生物启发的酵母胶囊（YC）的“特洛伊木马”策略，在多种疾病模型中靶向口服递送多种纳米颗粒。多种带电纳米探针，包括量子点（QD）、氧化铁纳米颗粒（IONP）和组装的有机荧光纳米颗粒，可以通过静电力驱动的自发沉积有效地装入 YC 中，从而形成不同的诊断 YC 组装体。此外，不同的正纳米疗法，包含抗炎药吲哚美辛（IND）或抗肿瘤药紫杉醇（PTX），也可以有效地被包装到 YC 中。含有纳米探针或纳米疗法的 YC 可以被巨噬细胞迅速内吞，并在细胞中维持较长时间。口服给药后，包装在 YC 中的纳米颗粒首先被 M 细胞转胞吞，然后被巨噬细胞内吞，然后运送到邻近的淋巴组织，并最终递送至小鼠或大鼠的炎症或肿瘤等远处病变部位，所有这些都是通过巨噬细胞激活、募集和部署的自然途径。对于所检查的急性炎症模型，与通过静脉注射给予相同剂量的对照纳米探针相比，YC 递送的 QD 或 IONP 的靶向效率甚至更高。通过 YC 口服递送的组装 IND 或 PTX 纳米疗法与炎症和肿瘤动物模型中的单独纳米疗法相比，表现出显著增强的疗效，这与药物分子在病变部位的靶向作用和增强积累一致。因此，通过复杂的运输途径，封装在 YC 中的纳米探针或纳米疗法可以优先递送至所需的靶标，从而显著提高与炎症相关的多种疾病的治疗效果。
