肿瘤微环境具有很大的异质性，特别是在比较转移部位时。确定这种异质性的程度可以为如何最好地设计基于脂质的药物递送系统来治疗转移性疾病提供指导。在我们之前的研究基础上，当前的研究采用转移性癌症的小鼠模型来探索 ~ 100 nm脂质体的分布。雌性NCr裸鼠接种了荧光标记的Her2/neu阳性、曲妥珠单抗耐药的乳腺癌细胞系，JIMT-1mkate，要么在乳腺脂肪垫中创建原位肿瘤（OT），要么通过心内注射（IC）在全身建立肿瘤。给动物服用荧光和放射性标记的脂质体。使用体内和离体荧光成像来追踪 48 小时内的脂质体分布。将原位肿瘤中的脂质体分布与 IC 注射后出现的肿瘤生长部位进行比较。观察到 DiR 分布的显着血管间异质性，大多数肿瘤血管几乎不存在 DiR 标记的脂质体。此外，DiR 脂质体在 DiR 阳性血管周围的血管周围区域的血管外分布有限。虽然所有 OT 肿瘤都至少含有一些 DiR 阳性血管，但许多转移瘤几乎没有或根本没有。尽管脂质体在转移灶内的分布明显有限，但两种脂质体药物制剂 Irinophore C 和 Doxil 对 OT 和 IC JIMT-1mkate 模型显示出相似的功效。这些发现表明，脂质体制剂通过超越增强的机制实现治疗益处。渗透性和保留效果。© 2024。作者。

The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes.Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-1mkate, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection.A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-1mkate models.These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect.© 2024. The Author(s).