Photosensitization Priming of Tumor Microenvironments Improves Delivery of Nanotherapeutics via Neutrophil Infiltration.

Photosensitization Priming of Tumor Microenvironments Improves Delivery of Nanotherapeutics via Neutrophil Infiltration.
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DOI:
10.1002/adma.201701021
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发表时间:
2017-07
期刊:
Advanced materials (Deerfield Beach, Fla.)
影响因子:
--
通讯作者:
Wang Z
Wang Z
中科院分区:
其他
文献类型:
--
作者:
Chu D;Dong X;Zhao Q;Gu J;Wang Z

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肿瘤微环境的重塑使得能够增强纳米颗粒(NP)的递送。该研究表明,使用光敏化直接引发肿瘤组织快速激活中性粒细胞浸润,其介导纳米治疗剂递送到肿瘤中。药物递送平台由包被有靶向活化中性粒细胞的抗CD 11b抗体(Ab)的NP组成。活体显微镜检查表明,抗CD 11b Abs修饰的NPs(NPs-CD 11b)进入肿瘤是由光敏化(PS)诱导的中性粒细胞浸润介导的,因为中性粒细胞的全身消耗完全消除了纳米颗粒肿瘤沉积。中性粒细胞对NP的摄取不改变中性粒细胞的活化和迁移。对于小鼠的癌症治疗,肿瘤PS和抗CD 11b Ab连接的金纳米棒(GNR-CD 11b)的光热疗法组合以治疗癌肿瘤。结果表明,中性粒细胞肿瘤浸润增强了纳米颗粒癌症治疗。研究结果表明,通过操纵肿瘤微环境来促进中性粒细胞的肿瘤浸润可能是一种在癌症治疗中积极提供纳米治疗药物的新策略。
Remodeling of tumor microenvironments enables enhanced delivery of nanoparticles (NPs). This study shows that direct priming of a tumor tissue using photosensitization rapidly activates neutrophil infiltration that mediates delivery of nanotherapeutics into the tumor. A drug delivery platform is comprised of NPs coated with anti‐CD11b antibodies (Abs) that target activated neutrophils. Intravital microscopy demonstrates that the movement of anti‐CD11b Abs‐decorated NPs (NPs‐CD11b) into the tumor is mediated by neutrophil infiltration induced by photosensitization (PS) because the systemic depletion of neutrophils completely abolishes the nanoparticle tumor deposition. The neutrophil uptake of NPs does not alter neutrophil activation and transmigration. For cancer therapy in mice, tumor PS and photothermal therapy of anti‐CD11b Abs‐linked gold nanorods (GNRs‐CD11b) are combined to treat the carcinoma tumor. The result indicates that neutrophil tumor infiltration enhances nanoparticle cancer therapy. The findings reveal that promoting tumor infiltration of neutrophils by manipulating tumor microenvironments could be a novel strategy to actively deliver nanotherapeutics in cancer therapies.
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