Chemotherapy drug (paclitaxel, PTX) incorporated in a dual functional polymeric nanocarrier, PEG-Fmoc-NLG, has shown promise as an immunochemotherapy in a murine breast cancer model, 4T1.2. The formulation is composed of an amphiphilic polymer with a built-in immunotherapy drug NLG919 that exhibits the immunostimulatory ability through the inhibition of indoleamine 2,3-dioxygenase 1 (IDO-1) in cancer cells. This work evaluates whether the PEG-derivatized NLG polymer can also be used for delivery of doxorubicin (Dox) in treatment of leukemia. The Dox-loaded micelles were self-assembled from PEG-Fmoc-NLG conjugate, which have a spherical shape with a uniform size of ∼120 nm. In cultured murine lymphocytic leukemia cells (A20), Dox-loaded PEG-Fmoc-NLG micelles showed a cytotoxicity that was comparable to that of free Dox. For in vivo studies, significantly improved antitumor activity was observed for the Dox/PEG-Fmoc-NLG group compared to Doxil or the free Dox group in an A20 lymphoma mouse model. Flow cytometric analysis showed that treatment with Dox/PEG-Fmoc-NLG micelles led to significant increases in the numbers of both total CD4⁺/CD8⁺ T cells and the functional CD4⁺/CD8⁺ T cells with concomitant decreases in the numbers of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (T_reg). Dox/PEG-Fmoc-NLG may represent a promising immunochemotherapy for lymphoma, which warrants more studies in the future.

中文翻译：

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淋巴瘤免疫化学疗法：通过双重功能的纳米载体靶向递送阿霉素。

掺入双功能聚合物纳米载体PEG-Fmoc-NLG中的化学治疗药物（紫杉醇，PTX）已在小鼠乳腺癌模型4T1.2中显示出作为免疫化学治疗的前景。该制剂由两亲性聚合物和内置的免疫治疗药物NLG919组成，该药物通过抑制癌细胞中的吲哚胺2,3-二加氧酶1（IDO-1）表现出免疫刺激能力。这项工作评估PEG衍生的NLG聚合物是否也可用于治疗白血病的阿霉素（Dox）的输送。载有Dox的胶束是由PEG-Fmoc-NLG共轭物自组装而成的，它们具有球形形状，均匀大小约为120 nm。在培养的鼠淋巴细胞白血病细胞（A20）中，载有Dox的PEG-Fmoc-NLG胶束显示出与游离Dox相当的细胞毒性。为了在体内研究中，在A20淋巴瘤小鼠模型中，与Doxil或游离Dox组相比，Dox / PEG-Fmoc-NLG组的抗肿瘤活性明显提高。流式细胞仪分析显示，用Dox / PEG-Fmoc-NLG胶束处理可显着增加总CD4 ⁺ / CD8 ⁺ T细胞和功能性CD4 ⁺ / CD8 ⁺ T细胞数量，同时髓样细胞数量减少来源的抑制细胞（MDSC）和调节性T细胞（T _reg）。Dox / PEG-Fmoc-NLG可能代表了一种有前途的淋巴瘤免疫化学疗法，值得在将来进行更多的研究。