黑色素瘤微环境（MME）内癌细胞和非肿瘤基质细胞之间错综复杂的合作促进了肿瘤的进展和转移。我们之前证明，通过使用封装磷酸泼尼松龙（PLP）（LCL-PLP）的长循环脂质体（LCL）可以破坏肿瘤相关巨噬细胞（TAM）和黑色素瘤细胞之间的相互作用，从而抑制TAM协调的肿瘤血管生成。在这项研究中，我们的目标是提高 LCL 对原肿瘤巨噬细胞（M2 样（即 TAM）巨噬细胞）的特异性，并通过将 PLP 加载到 IL-13 缀合的脂质体（IL-13- LCL-PLP)，因为 IL-13 受体在此类巨噬细胞中过度表达。 IL-13-LCL-PLP 脂质体制剂是通过将硫醇化 IL-13 共价连接到马来酰亚胺功能化的 LCL-PLP 上获得的。使用携带 B16.F10 s.c 黑色素瘤肿瘤的 C57BL/6 小鼠来研究 LCL-PLP 和 IL-13-LCL-PLP 的抗肿瘤作用。我们的结果表明，IL-13-LCL-PLP 制剂在 24 小时后在生物体液中保持稳定，并且优先被 M2 极化巨噬细胞吸收。与相同剂量的非功能化 LCL-PLP 相比，IL-13-LCL-PLP 通过改变 TAM 介导的血管生成和氧化应激、限制 MME 的细胞凋亡抵抗和侵袭特征，诱导强烈的肿瘤生长抑制。这些发现表明 IL-13-LCL-PLP 可能成为黑色素瘤化疗药物的一个有前景的递送平台。

The intricate cooperation between cancer cells and nontumor stromal cells within melanoma microenvironment (MME) enables tumor progression and metastasis. We previously demonstrated that the interplay between tumor-associated macrophages (TAMs) and melanoma cells can be disrupted by using long-circulating liposomes (LCLs) encapsulating prednisolone phosphate (PLP) (LCL-PLP) that inhibited tumor angiogenesis coordinated by TAMs. In this study, our goal was to improve LCL specificity for protumor macrophages (M2-like (i.e., TAMs) macrophages) and to induce a more precise accumulation at tumor site by loading PLP into IL-13-conjugated liposomes (IL-13-LCL-PLP), since IL-13 receptor is overexpressed in this type of macrophages. The IL-13-LCL-PLP liposomal formulation was obtained by covalent attachment of thiolated IL-13 to maleimide-functionalized LCL-PLP. C57BL/6 mice bearing B16.F10 s.c melanoma tumors were used to investigate the antitumor action of LCL-PLP and IL-13-LCL-PLP. Our results showed that IL-13-LCL-PLP formulation remained stable in biological fluids after 24h and it was preferentially taken up by M2 polarized macrophages. IL-13-LCL-PLP induced strong tumor growth inhibition compared to nonfunctionalized LCL-PLP at the same dose, by altering TAMs-mediated angiogenesis and oxidative stress, limiting resistance to apoptosis and invasive features in MME. These findings suggest IL-13-LCL-PLP might become a promising delivery platform for chemotherapeutic agents in melanoma.