Smart Nanodrug Combats Resistance

Smart Nanodrug Combats Resistance

Author: Chemistry – A European Journal

Nanodrugs for anticancer treatment can be stopped by a series of physiological barriers before achieving their intended therapeutic effect. Weihong Tan, Hunan University, China, Shanghai Jiao Tong University, China, and University of Florida, Gainesville, USA, and colleagues have developed a size-controllable and transformable “stealth” nanodrug based on multiple host-guest interactions.

The nanodrug is prepared by assembling three modules: First, a poly(amidoamine) (PAMAM) dendrimer is loaded with the anticancer drug doxorubicin (Dox). Secondly, the dendrimer is coated with adamantane (Ad)-modified chimera peptides, which consist of nuclear location peptides (NLS) and matrix metalloproteinase-2 (MMP-2)-responsive peptides. Finally, a β-cyclodextrin polymer and Ad-modified CD47 peptides are added. CD-47 acts as a “don’t eat me” signal to macrophages of the immune system. The final smart nanodrug forms by self-assembly.

The nanodrug can efficiently overcome multiple biological barriers. When it is near a tumor (pictured), the hybrid drug disassembles into smaller components (DOX/PAMAM‐NLS), which enter the tumor cells. This disassembly is caused by a reaction to MMP-2, which has a higher concentration near tumors. The nanodrug, thus, successfully overcomes drug resistance. This study provides a promising strategy for designing smart and efficient nanodrugs to treat cancers.


 

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