Institute of Chemistry, Academia Sinica – Research
可黏附單核細胞之多肽微脂體應用腫瘤治療
Monocyte-adhesive peptidyl liposomes for harnessing monocyte homing to tumor tissuesJournal of Controlled Release 2025, 382, 113672
Chia-Yu Chang, Shih-Hsun Huang, Chong-Yan Chen, Cheng-Bang Jian, Ching-Chung Chang, Yu-Yao Chang, Mira Jung, Hsien-Ming Lee*, Bill Cheng*

In current drug delivery strategies, the efficiency of most carriers still largely depends on their ability to passively infiltrate target tissues. To overcome this limitation, we developed monocyte-adhesive peptidyl liposomes, termed monocyte-mediated drug carriers (MMDCs). These carriers are designed to exploit the innate chemotactic properties of monocytes, which actively home to diseased tissues. MMDCs were shown to effectively hitchhike on circulating monocytes (THP-1 cells) under physiological flow conditions. Their targeting specificity was further demonstrated in a 3D microfluidic culture system consisting of human breast cancer spheroids (MDA-MB-231) embedded in a collagen matrix, overlaid with a human endothelial cell-derived barrier. MMDCs underwent trans-endothelial migration via monocyte hitchhiking and selectively recognized collagen matrices containing MDA-MB-231 cells, but not those embedded with non-cancerous cells. In vitro assays revealed that doxorubicin encapsulated in MMDCs was released into the extracellular environment following phagocytosis of the carriers by THP-1-derived macrophages. In a xenograft mouse model, MMDCs exhibited high tumor-targeting efficiency. By harnessing the homing capability of monocytes, MMDCs significantly improved drug biodistribution at the disease site, thereby enhancing the therapeutic efficacy of the encapsulated agents.
在現行的藥物傳遞策略中,大多數載體的效率仍主要依賴其被動滲透至目標組織的能力。為了克服這一限制,我們開發了具單核白血球黏附性的多肽微脂體。這些多肽微脂體旨在利用單核白血球的先天趨向疾病組織細胞激素特性,主動靶向至病變組織。研究顯示,我們多肽微脂體在生理流動條件下能有效搭載於循環中的單核白血球(THP-1 細胞)上。其靶向特異性進一步在一個三維微流體培養系統中得到驗證。我們多肽微脂體可透過單核球搭載方式穿越內皮層,並選擇性辨識含有 MDA-MB-231 細胞的膠原基質,而選擇性不靶向嵌有非癌細胞的基質。體外試驗顯示,當載有微脂體的單核細胞並不會內吞微脂體,但發炎因子將單核細胞轉換成巨噬細胞後,微脂體被吞噬,而封裝於其中的多柔比星(doxorubicin)可釋放至細胞外環境進行化療。在異種移植小鼠模型中,我們的微脂體展現出高度腫瘤靶向效率。透過利用單核細胞的靶向能力,所承載的微脂體可顯著提升藥物在病灶部位的生物分佈,進而增強所封裝藥物的治療效力。