Dual Near-Infrared Light-Activated Upconversion Nanorobots for Active Synergistic Phototherapy

Phototherapy represents a non-invasive and flexible treatment for superficial tumors. However, application for deep-seated tumor therapy is limited by low efficiency of photosensitizer delivery and activation barrier as shallow penetration of light in biological tissue. Here, a dual near-infrared (NIR) light-responsive, breast cancer cell membrane (Cm)-coated upconversion nanorobot (CUCNbot), for photosensitizer delivery and synergistic photothermal therapy (PTT)/photodynamic therapy (PDT) is presented. UCNbots features a Janus core-shell structure, consisting of an upconversion nanoparticle core and a gold half-coated mesoporous silica shell. Upon 808 nm NIR light irradiation, the photothermal effect of gold half-shell not only creates a heat gradient to drive the photo-thermophoresis of CUCNbots but also enables PTT. The photosensitizer precursor, 5-aminolevulinic acid (5-ALA), is encapsulated within UCNbots and retained by Cm coating, which imparts CUCNbots to homologously target tumor for deep penetration. Once internalized by tumor cells, 5-ALA is metabolized into protoporphyrin through intrinsic biosynthetic pathway in mitochondria, activating PDT under visible light emitted by UCNP core upon 980 nm NIR light irradiation, resulting in 8.8-fold increase of treatment efficiency. As such, CUCNbots overcome the barrier of light penetration in biological tissue to achieve synergistic PTT/PDT, while reducing the doses of therapeutic agents and establishing a precise tumor treatment.