Zhu Saijie, Niu Mengmeng, O'Mary Hannah, Cui Zhengrong
Pharmaceutics Division, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, United States.
Mol Pharm. 2013 Sep 3;10(9):3525-30. doi: 10.1021/mp400216r. Epub 2013 Aug 6.
It is increasingly evident that tumor-associated macrophages (TAMs) play an important role in tumor invasion, proliferation, and metastasis. While delivery of drugs, imaging agents, and vaccines to TAMs was achieved by exploiting membrane receptors on TAMs, the uptake by normal macrophages remains an issue. In this communication, we report a PEG-sheddable, mannose-modified nanoparticle platform that can efficiently target TAMs via mannose-mannose receptor recognition after acid-sensitive PEG shedding in the acidic tumor microenvironment, while their uptake by normal macrophages in the mononuclear phagocyte system (MPS) organs was significantly reduced due to effective PEG shielding at neutral pH. These nanoparticles have the potential to target drugs of interest to TAMs, with decreased uptake by normal macrophages.
越来越明显的是，肿瘤相关巨噬细胞（TAM）在肿瘤侵袭、增殖和转移中发挥着重要作用。虽然通过利用TAM上的膜受体实现了向TAM递送药物、成像剂和疫苗，但正常巨噬细胞的摄取仍然是一个问题。在本通讯中，我们报道了一种可PEG脱落、甘露糖修饰的纳米颗粒平台，该平台在酸性肿瘤微环境中经酸敏性PEG脱落后，可通过甘露糖-甘露糖受体识别有效地靶向TAM，而由于在中性pH下有效的PEG屏蔽，单核吞噬细胞系统（MPS）器官中的正常巨噬细胞对其摄取显著减少。这些纳米颗粒有潜力将感兴趣的药物靶向TAM，同时减少正常巨噬细胞的摄取。
