Self‐Assembled Nanoconjugates with Aggregation‐Induced Emission for Near‐Infrared II Imaging and Transcytosis‐Driven Cancer Therapy
Abstract
Abstract Nanomedicine holds immense potential to revolutionize cancer therapy, yet its clinical translation remains hampered by insufficient tumor accumulation and an inability to dynamically monitor therapeutic penetration. While transcytosis‐mediated transport offers a promising strategy to overcome biological barriers, existing carriers lack real‐time imaging capabilities, particularly in the near‐infrared II window, to guide optimization. Herein, we address this dual challenge through a multifunctional poly[L‐γ‐[2‐( N ‐oxide‐ N,N ‐dimethylamino)ethyl]glutamine]‐paclitaxel (OPGAX) conjugate integrated with aggregation‐induced emission (AIE) luminogens. The OPGAX conjugate self‐assembled into uniform nanoparticles (NPs) with a high drug‐loading capacity (42.5%) and intense near‐Infrared II (NIR‐II) fluorescence (1000–1350 nm). The zwitterionic tertiary amine oxide (TAO) moiety endowed OPGAX with protein resistance and cell membrane affinity, leading to prolonged blood circulation and enhanced tumor accumulation. OPGAX NPs performed NIR‐II imaging to visualize whole‐body vasculature and dynamically track tumor penetration. In 4T1 tumor‐bearing mice, OPGAX NPs achieved deep tumor infiltration via transcytosis, visualized dynamically by NIR‐II imaging, and suppressed tumor growth. This platform bridges diagnostic certainty with therapeutic efficacy, offering a translatable strategy for image‐guided precision oncology.
Article Details
Authors (12)
Guiping Yuan
Department of Chemistry, and the Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction
Wutong Du
Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Division of Life Science, State Key Laboratory of Molecular Neuroscience, and Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China
Feiyi Sun
Department of Comprehensive Basic Experiment The Ninth Medical Center of Chinese PLA General Hospital Beijing 100101 China
Qiuyang Dong
Zhejiang Key Laboratory of Smart Biomaterials Center for Bionanoengineering Key Laboratory of Biomass Chemical Engineering of the Ministry of Education College of Chemical and Biological Engineering Zhejiang University Hangzhou 310058 China
Cheng Liu
Yingni Xu
Department of Chemistry Department of Chemical and Biological Engineering Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction Division of Life Science and State Key Laboratory of Molecular Neuroscience The Hong Kong University of Science and Technology Hong Kong Kowloon 999077 China
Chunxi Liu
Jacky W. Y. Lam
Department of Chemistry, the Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Department of Chemical and Biological Engineering, State Key Laboratory of Nervous System Disorders, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR 999077, China
Jianwei Sun
Jiajia Xiang
Ryan T. K. Kwok
Department of Chemistry, the Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Department of Chemical and Biological Engineering, State Key Laboratory of Nervous System Disorders, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR 999077, China
Ben Zhong Tang
School of Science and Engineering, Guangdong Basic Research Center of Excellence for Aggregate Science, The Chinese University of Hong Kong (Shenzhen), Longgang, Shenzhen 518172, Guangdong, P. R. China