Targeted codelivery of doxorubicin and IL-36γ expression plasmid for an optimal chemo-gene combination therapy against cancer lung metastasis.
Targeted codelivery of doxorubicin and IL-36γ expression plasmid for an optimal chemo-gene combination therapy against cancer lung metastasis.
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DOI：
10.1016/j.nano.2018.09.005
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发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Chen Y;Sun J;Huang Y;Liu Y;Liang L;Yang D;Lu B;Li S
肿瘤转移是乳腺癌患者死亡率高的主要原因。本工作中，我们开发了一种聚合物POEG-st-Pmor，用于靶向共递送IL-36γ表达质粒和多柔比星（Dox）到乳腺癌的肺转移。该聚合物容易形成胶束，其有效地负载Dox并同时与IL-36γ质粒形成复合物。有趣的是，共负载有Dox和质粒的颗粒比仅负载有Dox的颗粒显著更小且更稳定。在两个肺和s.c.与PEI相比，使用我们的聚合物的肿瘤显著更高。此外，Dox+IL-36γ/POEG-st-Pmor不仅可以带来改善的抗转移效果，而且可以通过增加IFN-γ阳性的CD 4+和CD 8 + T细胞，同时减少肺中免疫抑制性骨髓来源的抑制细胞，协同增强I型免疫应答。POEG-st-Pmor可能是一种简单有效的化疗-基因联合治疗系统。
Cancer metastasis is the main cause for the high mortality in breast cancer patients. In this work we developed a polymer POEG-st-Pmor for targeted co-delivery of IL-36γ expression plasmid and doxorubicin (Dox) to lung metastasis of breast cancer. The polymer readily formed micelles that were effective in loading Dox and simultaneously forming complexes with IL-36γ plasmid. Interestingly, particles co-loaded with Dox and plasmid was significantly smaller and more stable than the particles loaded with Dox only. Gene transfection in both lungs and s.c. tumors was significantly higher with our polymer compared to PEI. In addition, the Dox+IL-36γ/POEG-st-Pmor could not only bring improved anti-metastatic effect but synergistically enhance the type I immune response by increasing the IFN-γ positive CD4+ and CD8+ T cells and simultaneously decreasing the immunosuppressive myeloid-derived suppressor cells in the lung. POEG-st-Pmor may represent a simple and effective delivery system for an optimal chemo-gene combination therapy.
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