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Background <p>Lung adenocarcinoma (LUAD) is a refractory tumor with high incidence, high mortality, and easy development of drug resistance. Represented by PD-L1, the rise of immunotherapy and multidrug combinations offers a reliable approach to treating LUAD. However, there are still some patients with immunoresistance or insensitivity, and new combination therapies are still needed.</p> Methods <p>In this study, cyclic arginine-glycine-aspartate (cRGD)/erythrocyte membrane (RBCM) double-head nanocarriers were designed. This nanocarrier platform targets CTRP6 in tumors and delivers gemcitabine to block the progression of lung cancer. PD-L1 monoclonal antibodies were used as a codelivery platform to explore the effect of the codelivery platform on immunotherapy.</p> Results <p>CTRP6 expression was negatively correlated with the prognosis of patients with lung adenocarcinoma. The codelivery platform @RBCM/cRGD-PhLips effectively targeted tumor cells. Co-carrying gemcitabine and targeting CTRP6 expression, it amplified ferroptosis of tumor cells through the NRF2/STAT3 signaling pathway, activated intratumoral immunity, and promoted M1-like macrophage transformation and CD8<sup>+</sup> T-cell recruitment. This platform amplified the immune effect of PD-L1 monoclonal antibodies to play an anti-lung cancer role.</p> Conclusions <p>The synergistic delivery of the targeted tumor cell-intrinsic CTRP6 biomimetic nanocarrier provides a new approach to the combined immunotherapy of lung cancer.</p> Graphical Abstract <p></p>

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Targeted tumor cell-intrinsic CTRP6 biomimetic codelivery synergistically amplifies ferroptosis and immune activation to boost anti-PD-L1 immunotherapy efficacy in lung cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月2日

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  • Songhua Cai,
  • Jing Huang,
  • Hongjie Fan,
  • Zhilin Sui,
  • Chujian Huang,
  • Youjun Deng,
  • Ran Jia,
  • Lixu Wang,
  • Kai Ma,
  • Xiaotong Guo,
  • Jie He,
  • Baihua Zhang,
  • Zhentao Yu

摘要

Background

Lung adenocarcinoma (LUAD) is a refractory tumor with high incidence, high mortality, and easy development of drug resistance. Represented by PD-L1, the rise of immunotherapy and multidrug combinations offers a reliable approach to treating LUAD. However, there are still some patients with immunoresistance or insensitivity, and new combination therapies are still needed.

Methods

In this study, cyclic arginine-glycine-aspartate (cRGD)/erythrocyte membrane (RBCM) double-head nanocarriers were designed. This nanocarrier platform targets CTRP6 in tumors and delivers gemcitabine to block the progression of lung cancer. PD-L1 monoclonal antibodies were used as a codelivery platform to explore the effect of the codelivery platform on immunotherapy.

Results

CTRP6 expression was negatively correlated with the prognosis of patients with lung adenocarcinoma. The codelivery platform @RBCM/cRGD-PhLips effectively targeted tumor cells. Co-carrying gemcitabine and targeting CTRP6 expression, it amplified ferroptosis of tumor cells through the NRF2/STAT3 signaling pathway, activated intratumoral immunity, and promoted M1-like macrophage transformation and CD8+ T-cell recruitment. This platform amplified the immune effect of PD-L1 monoclonal antibodies to play an anti-lung cancer role.

Conclusions

The synergistic delivery of the targeted tumor cell-intrinsic CTRP6 biomimetic nanocarrier provides a new approach to the combined immunotherapy of lung cancer.

Graphical Abstract