Guo Yunfei, Li Yiming, Li Jianmin, Cai Haoran, Liu Kangkang, Duan Dengyi, Zhang Wenyi, Han Gang, Zhao Yang
Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, P. R. China.
Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, P. R. China.
Adv Sci (Weinh). 2025 Mar;12(11):e2411307. doi: 10.1002/advs.202411307. Epub 2025 Jan 12.
Tumor heterogeneity remains a formidable obstacle in targeted cancer therapy, often leading to suboptimal treatment outcomes. This study presents an innovative approach that harnesses controlled inflammation to guide neutrophil-mediated drug delivery, effectively overcoming the limitations imposed by tumor heterogeneity. By inducing localized inflammation within tumors using lipopolysaccharide, it significantly amplify the recruitment of drug-laden neutrophils to tumor sites, irrespective of specific tumor markers. This strategy not only enhances targeted drug delivery but also triggers the release of neutrophil extracellular traps, further potentiating the anti-tumor effect. Crucially, this study demonstrates that potential systemic inflammatory responses can be effectively mitigated through neutrophil transfusion, ensuring the safety and clinical viability of this approach. In a murine breast cancer model, the method significantly impedes tumor growth compared to conventional treatments. This work offers a versatile strategy for precise drug delivery across diverse tumor types. The findings pave the way for more effective and broadly applicable cancer treatments, potentially addressing the long-standing challenge of tumor heterogeneity.
肿瘤异质性仍然是靶向癌症治疗中的一个巨大障碍，常常导致治疗效果欠佳。本研究提出了一种创新方法，该方法利用可控炎症来引导中性粒细胞介导的药物递送，有效克服了肿瘤异质性带来的限制。通过使用脂多糖在肿瘤内诱导局部炎症，无论特定肿瘤标志物如何，都能显著增加载药中性粒细胞向肿瘤部位的募集。这种策略不仅增强了靶向药物递送，还触发了中性粒细胞胞外陷阱的释放，进一步增强了抗肿瘤效果。至关重要的是，这项研究表明，通过中性粒细胞输血可以有效减轻潜在的全身炎症反应，确保这种方法的安全性和临床可行性。在小鼠乳腺癌模型中，与传统治疗方法相比，该方法显著抑制了肿瘤生长。这项工作为跨多种肿瘤类型的精确药物递送提供了一种通用策略。这些发现为更有效、更广泛适用的癌症治疗铺平了道路，有可能解决肿瘤异质性这一长期挑战。
