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.