Nanoparticle Targeting of Neutrophils for Improved Cancer Immunotherapy.
Nanoparticle Targeting of Neutrophils for Improved Cancer Immunotherapy.
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DOI：
10.1002/adhm.201500998
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发表时间：
2016-05
影响因子：
10
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Chu D;Zhao Q;Yu J;Zhang F;Zhang H;Wang Z
利用肿瘤特异性单克隆抗体（mAbs）进行癌症免疫治疗为癌症治疗提供了一种新方法。一种针对黑色素瘤gp75抗原的特异性单克隆抗体TA99，可引发肿瘤中负责癌症治疗的中性粒细胞募集。在此，我们报告一种在体内利用纳米颗粒（NPs）劫持中性粒细胞，从而将治疗药物输送至肿瘤的策略。在黑色素瘤小鼠模型中，我们发现，注射TA99抗体后，经全身递送的白蛋白纳米颗粒在肿瘤中的含量增加；且纳米颗粒在肿瘤中的积聚是由中性粒细胞介导的。与单独使用纳米颗粒或TA99治疗相比，给予负载焦脱镁叶绿酸-a（Ppa）的白蛋白纳米颗粒和TA99后，光动力疗法显著抑制了肿瘤生长并提高了小鼠存活率。该研究揭示了一种通过纳米颗粒借助免疫系统，增强治疗药物向肿瘤部位递送从而治疗癌症的新途径。
Cancer immunotherapy using tumor specific monoclonal antibodies (mAbs) presents a novel approach for cancer treatment. A monoclonal antibody TA99 specific for gp75 antigen of melanoma, initiates neutrophil recruitment in tumor responsible for cancer therapy. Here we report a strategy for hijacking neutrophils in vivo using nanoparticles (NPs) to deliver therapeutics into tumor. In a mouse model of melanoma, we showed that systemically delivered albumin NPs increased in tumor when TA99 antibody was injected; and the nanoparticle tumor accumulation was mediated by neutrophils. After the administration of pyropheophorbide-a (Ppa) loaded albumin NPs and TA99, photodynamic therapy significantly suppressed the tumor growth and increased mouse survival compared with treatment with the NPs or TA99. The study reveals a new avenue to treat cancer by nanoparticle hitchhiking of immune systems to enhance delivery of therapeutics into tumor sites.