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Double‐Targeting Explosible Nanofirework for Tumor Ignition to Guide Tumor‐Depth Photothermal Therapy
Authors:Ming‐Kang Zhang  Xiao‐Gang Wang  Jing‐Yi Zhu  Miao‐Deng Liu  Chu‐Xin Li  Jun Feng  Xian‐Zheng Zhang
Affiliation:Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, P.R. China
Abstract:This study reports a double‐targeting “nanofirework” for tumor‐ignited imaging to guide effective tumor‐depth photothermal therapy (PTT). Typically, ≈30 nm upconversion nanoparticles (UCNP) are enveloped with a hybrid corona composed of ≈4 nm CuS tethered hyaluronic acid (CuS‐HA). The HA corona provides active tumor‐targeted functionality together with excellent stability and improved biocompatibility. The dimension of UCNP@CuS‐HA is specifically set within the optimal size window for passive tumor‐targeting effect, demonstrating significant contributions to both the in vivo prolonged circulation duration and the enhanced size‐dependent tumor accumulation compared with ultrasmall CuS nanoparticles. The tumors featuring hyaluronidase (HAase) overexpression could induce the escape of CuS away from UCNP@CuS‐HA due to HAase‐catalyzed HA degradation, in turn activating the recovery of initially CuS‐quenched luminescence of UCNP and also driving the tumor‐depth infiltration of ultrasmall CuS for effective PTT. This in vivo transition has proven to be highly dependent on tumor occurrence like a tumor‐ignited explosible firework. Together with the double‐targeting functionality, the pathology‐selective tumor ignition permits precise tumor detection and imaging‐guided spatiotemporal control over PTT operation, leading to complete tumor ablation under near infrared (NIR) irradiation. This study offers a new paradigm of utilizing pathological characteristics to design nanotheranostics for precise detection and personalized therapy of tumors.
Keywords:double targeting  nanofirework  photothermal therapy (PTT)  tumor‐depth infiltration  tumor‐ignited imaging
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