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

Abstract 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.