Acid-triggered size reduction of nanomedicines for enhancing tumor therapy efficacy

Nanomedicines whose size can be varied on demand may synchronously achieve excellent tumor accumulation and penetration. In this study, by taking advantage of the pH sensitivity of a boronate ester, we synthesized acid-triggered size-reducing polymer nanoparticles (named PCD) by cross-linking β-cyclodextrin-cored multiarm polymers through the boronate ester. In PCD, the antitumor agent doxorubicin was loaded <i>via</i> the pH-sensitive hydrazone linkage. The <i>in vitro</i> and <i>in vivo</i> properties of PCD were investigated using a non-responsive nanoparticle (named UCD) as a reference. In the neutral condition of the bloodstream, PCD was stable and exhibited a suitable size for long circulation time. Upon entering tumors, PCD decomposed into stable and smaller multiarm polymers, which could deeply penetrate tumors. The high tumor accumulation and penetration of PCD offered significantly better anti-tumor efficacy than UCD.