Efficient Remote NIR-Controlled Drug Delivery Into Tumor Cells by Nanoplatform Modified with Tumoral-Acid-Cleavable Polyethylene Glycol

Despite advances in controlled drug delivery, drug-delivery systems with controlled activatable drug release and high spatial and temporal resolution are still required. PEGylation has been extensively used to increase the circulation time of controlled drug-delivery systems, but polyethylene glycol (PEG) is unsuitable for uptake by tumor cells because it causes steric hindrance. In this study, a near-infrared (NIR)-light-regulated drug-delivery system with enhanced cellular uptake was developed using a hybrid nanoplatform (GO@Au). GO@Au modified with tumoral-acid-cleavable PEG circumvents the hindrance effect of PEG grafted onto the drug-delivery system without sacrificing the property of a long circulation time. With the application of NIR light, both GO and Au in GO@Au strongly absorb the NIR energy, leading to intense resonance, and causing the release of a significant proportion of the loaded drug. GO@Au retains most of the loaded drug without NIR. We show the feasibility of using this nanocarrier as a targeted, noninvasive remote-controlled drug-delivery system with high spatial and temporal resolution. Integrating chemotherapy and photothermal therapy functions into one system, we investigated the therapeutic effects of DOX-loaded GO@Au–PEG, with highly efficient drug loading. Our in vitro and in vivo results reveal a synergistic effect, enhancing the therapeutic effects of the drugs and reducing their adverse effects. These results highlight the great potential utility of GO@Au–PEG/DOX in the treatment of cancer.