The main goal of cancer nanomedicine today is to improve the efficacy of anticancer drugs while limiting their side effects. Although tumours are difficult to penetrate, researchers have succeeded in improving drug uptake in recent years by using surface modified nanovectors with targeting ligands (such as folic acid) or cell-penetrating peptides (like TAT). However, the problem is that ligand-modified nanoparticles may adversely interact with serum proteins and normal, healthy tissue.

To overcome these problems, a team led by Haijun Yu and Yaping Li of the Shanghai Institute of Materia Medica has now developed acidity-triggered ligand-presenting (ATLP) nanoparticles for cancer therapy. The ATLP particles are composed of an acid-responsive diblock polymer (the polymer matrix) and an iRGD-modified polymeric prodrug of doxorubicin (iPDOX) as an amphiphilic core. The iRGD is a nine-amino-acid-based cyclic, tumour specific homing, arginine-glycine-aspartic acid (RGD)-based peptide (CRGDKRGPDC). A PEG shell surrounding the polymer matrix, protects the iRGD ligand from being degraded by serum proteins and prevents it from interacting with normal tissue while it is circulating in the bloodstream.

The EPR effect and acid-triggered dissociation of the polymer matrix

In experiments on tumour-bearing mice, the researchers found that the ATLP nanoparticles specifically accumulate at a tumour site thanks to the enhanced permeability and retention (EPR) effect, followed by acid-triggered dissociation of the polymer matrix within the acidic microenvironment of the tumour (which is around 6.8). This dissociation exposes the iRGD ligand, so that the iPDOX prodrug can penetrate the tumour more easily, leading to improved uptake.

The team, reporting its work in Nano Letters DOI: 10.1021/acs.nanolett.7b02031, says that it is now continuing to design other novel intelligent nanoparticles. "We hope that these new particles will have a better biocompatibility than the ones we have made so far," Yu tells