Particle-in-Particle Platform for Nanoconfinement-Induced Oncothermia

Oncothermia, a special form of hyperthermia for oncological purposes, has been widely shown to be an effective mode of cancer therapy. However, its adoption among standard therapeutic practices has been limited by constraints in delivering sufficient thermal energy to tumor targets. To overcome these unique challenges in delivery presented by oncothermic therapeutics, we engineered a novel universal platform for hyperthermia cancer therapy utilizing versatile biocompatible materials. Herein, we show that Gold particle-in-particle (PIP), in which gold nanoparticles are physically confined within PLGA-PEG nanoparticles, significantly enhances thermal energy production by red-shifting the gold nanoparticle's absorption spectra via a mechanism in which we call nanoconfinement-induced therapeutic enhancement (NITE). NITE mediated Gold PIPs significantly suppress breast, skin, and multidrug resistant tumors and result in a multifold increase of heat shock protein expressed by cancer cells in vivo. Cotreatment of Gold PIP with doxorubicin shows a synergistic advantage. By using tumor-bearing mice, significant suppression of tumor growth by Gold PIPs shows the advantage of NITE mediated hyperthermia. Thus, we conclude that NITE mediated Gold PIP can be a strong anticancer therapy because of its sufficient amount of heat generation.