Targeted and imaging-guided chemo-photothermal ablation achieved by combining upconversion nanoparticles and protein-capped gold nanodots

Abstract

For precise targeting therapy, nanocarriers are typically employed to realize tumor-guided delivery of chemotherapeutic drugs, which should ideally kill cancer cell without side effect under controlled release. Besides, as the temperature is fatal for photothermal therapy (PTT), enhancing photothermal conversion efficiency is essential for improving PTT efficacy. Moreover, as PTT is a localized therapy technique, maintaining high penetration depth and simultaneously achieving multimodal imaging during theranostics are conducive to clinical application. Aiming at resolving these plaguing challenges, here we developed a novel anti-tumor platform by combining upconversion nanoparticles with protein-capped gold nanodots through a facile route, following by loading chemotherapeutic drug (doxorubicin, DOX) and conjugating targeting agent (folic acid, FA). Such nanoplatform with luminescence resonance energy transfer (LRET) effect showed enhanced PTT efficacy under near-infrared (NIR) laser irradiation, and FA conjugation is capable of further targeting cancer cells, namely the focus location in vivo. Meanwhile, the nanocarrier with pH-sensitive DOX release ability would contribute to intensive release responding to acidic tumor microenvironment assisted by NIR light excitation induced heat effect, further improving in vivo anti-tumor efficiency. Additionally, by combining our upconversion/Au nanohybrid with multimodal imaging, direct cancer cell killing responses could be obtained at a deeper penetration depth, promising for completely inhibiting tumor proliferation.