Hierarchical Targeting Strategy for Enhanced Tumor Tissue Accumulation/Retention and Cellular Internalization

• Published in: Advanced materials (Weinheim) Vol. 28; no. 34; pp. 7340 - 7364
• Main Authors: Wang, Sheng, Huang, Peng, Chen, Xiaoyuan
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 01.09.2016
• Subjects: activatable surface ligands; changeable particle sizes; Drug Delivery Systems; hierarchical targeting; Humans; Ligands; Nanoparticles; Nanostructure; Neoplasms; Particle Size; Stimuli; stimuli-responsive nanoplatforms; Strategy; Surface chemistry; switchable surface charges; Tumor Microenvironment; Tumors; changeable particle sizes; stimuli-responsive nanoplatforms; switchable surface charges; hierarchical targeting; activatable surface ligands
• ISSN: 0935-9648; 1521-4095; 1521-4095
• DOI: 10.1002/adma.201601498

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. Hierarchical targeting, which combines the advantages of both enhanced tumor‐tissue accumulation/retention and enhanced cellular internalization, is a promising strategy to improve the tumor‐targeting efficiency of nanoparticles. The different strategies are summarized, including the exploitation of changeable particle sizes, switchable surface charges, and activatable surface ligands to develop hierarchical targeting nanoplatforms.