Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology

被引:2172
作者
Bertrand, Nicolas [1 ]
Wu, Jun [2 ]
Xu, Xiaoyang [1 ,2 ]
Kamaly, Nazila [2 ]
Farokhzad, Omid C. [2 ]
机构
[1] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA
[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Nanomed & Biomat,Dept Anesthesiol, Boston, MA 02115 USA
基金
加拿大健康研究院;
关键词
Enhanced permeation and retention effect; Active targeting; Nanopartides; Nanomedicine; Personalized medicine; Tumor microenvironment; Drug delivery; Patient enrichment; Vessel normalization; Imaging; PEGYLATED LIPOSOMAL DOXORUBICIN; HIGH INTRATUMORAL ACCUMULATION; POLYMER HYBRID NANOPARTICLES; TUMOR VASCULAR-PERMEABILITY; FOLATE RECEPTOR EXPRESSION; PROLONGED CIRCULATION TIME; ANTI-EGFR IMMUNOLIPOSOMES; PLGA-PEG NANOPARTICLES; DRUG-DELIVERY SYSTEMS; IN-VITRO SELECTION;
D O I
10.1016/j.addr.2013.11.009
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cancer nanotherapeutics are progressing at a steady rate; research and development in the field has experienced an exponential growth since early 2000's. The path to the commercialization of oncology drugs is long and carries significant risk; however, there is considerable excitement that nanoparticle technologies may contribute to the success of cancer drug development The pace at which pharmaceutical companies have formed partnerships to use proprietary nanoparticle technologies has considerably accelerated. It is now recognized that by enhancing the efficacy and/or tolerability of new drug candidates, nanotechnology can meaningfully contribute to create differentiated products and improve clinical outcome. This review describes the lessons learned since the commercialization of the first-generation nanomedicines including DOXIL (R) and Abraxane (R). It explores our current understanding of targeted and non-targeted nanopartides that are under various stages of development, including BIND-014 and MM-398. It highlights the opportunities and challenges faced by nanomedicines in contemporary oncology, where personalized medicine is increasingly the mainstay of cancer therapy. We revisit the fundamental concepts of enhanced permeability and retention effect (EPR) and explore the mechanisms proposed to enhance preferential "retention" in the tumor, whether using active targeting of nanopartides, binding of drugs to their tumoral targets or the presence of tumor associated macrophages. The overall objective of this review is to enhance our understanding in the design and development of therapeutic nanoparticles for treatment of cancers. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:2 / 25
页数:24
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