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Transformable nanotherapeutics enabled by ICG: towards enhanced tumor penetration under NIR light irradiation.

Tumor penetration is the bottleneck for current cancer nanomedicine, limiting the ultimate antitumor efficacy in the clinic. Herein, by exploiting the well-known instability of indocyanine green (ICG), we report the preparation of near infrared (NIR) light responsive nanoparticles (NP) for enhanced tumor penetration. ICG crosslinks hydroxyethyl starch (HES) and doxorubicin (DOX) conjugates (HES-SS-DOX) via noncovalent interactions, facilitating the formation of ICG@HES-SS-DOX NP. The light triggered degradation of ICG leads to the dissociation of such NP, and the resulting HES-SS-DOX has been shown to penetrate deeper in both H22 tumor spheroids and tumor bearing mice, due to the photothermal effect of ICG. Therefore, the disintegrable ICG@HES-SS-DOX NP have better tumor penetration capacity than their counterparts, which originally cannot dissociate under NIR light stimulation. The reported ICG@HES-SS-DOX NP might be potent in treating malignant tumors with dense extracellular matrices, such as liver and pancreatic cancers. This study opens up a novel functionality of FDA-approved ICG for cancer nanotherapeutics.