title: Hierarchical Targeting Strategy for Enhanced Tumor Tissue Accumulation/Retention and Cellular Internalization.
abstract: Targeted delivery of therapeutic agents is an important way to improve the therapeutic index and reduce side effects. To design nanoparticles for targeted delivery, both enhanced tumor tissue accumulation/retention and enhanced cellular internalization should be considered simultaneously. So far, there have been very few nanoparticles with immutable structures that can achieve this goal efficiently. Hierarchical targeting, a novel targeting strategy based on stimuli responsiveness, shows good potential to enhance both tumor tissue accumulation/retention and cellular internalization. Here, the recent design and development of hierarchical targeting nanoplatforms, based on changeable particle sizes, switchable surface charges and activatable surface ligands, will be introduced. In general, the targeting moieties in these nanoplatforms are not activated during blood circulation for efficient tumor tissue accumulation, but re-activated by certain internal or external stimuli in the tumor microenvironment for enhanced cellular internalization.
authors.affiliation: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060, P. R. China.|Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, P. R. China.|Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060, P. R. China. peng.huang@szu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, 20892, USA. shawn.chen@nih.gov.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D016503:Drug Delivery Systems; D006801:Humans; D053758:Nanoparticles; D009369:Neoplasms; D010316:Particle Size; D059016:Tumor Microenvironment
keywords: activatable surface ligands; changeable particle sizes; hierarchical targeting; stimuli-responsive nanoplatforms; switchable surface charges