Affiliation:
1. Beijing National Laboratory for Molecular Sciences Laboratory of Polymer Physics and Chemistry Institute of Chemistry Chinese Academy of Sciences Beijing 100190 P. R. China
2. University of Chinese Academy of Sciences Beijing 100049 P. R. China
Abstract
AbstractPhotodynamic therapy (PDT) and photothermal therapy (PTT) leverage reactive oxygen species (ROS) and control local hyperthermia by photosensitizer to perturb intracellular redox equilibrium, inducing DNA damage in both mitochondria and nucleus, activating the cGAS‐STING pathway, ultimately eliciting antitumor immune responses. However, current photosensitizers are encumbered by limitations such as suboptimal tumor targeting, aggregation‐caused quenching (ACQ), and restricted excitation and emission wavelengths. Here, this work designs novel nanoparticles based on aggregation‐induced emission (AIE) photosensitizer (BODTPE) for targeted tumor therapy and near‐infrared II fluorescence imaging (NIR‐II FLI) with enhanced PDT/PTT effects. BODTPE is employed as a monomer, dibenzocyclooctyne (DBCO)‐PEG2k‐amine serving as an end‐capping polymer, to synthesize a BODTPE‐containing polymer (DBD). Further, through self‐assembly, DBD and mPEG‐DSPE2k combined to form nanoparticles (NP‐DBD). Notably, the DBCO on the surface of NP‐DBD can react with azide groups on cancer cells pretreated with Ac4ManNAz through a copper‐free click reaction. This innovative formulation led to targeted accumulation of NP‐DBD within tumor sites, a phenomenon convincingly demonstrated in murine tumor models subjected to N‐azidoacetylmannosamine‐tetraacylated (Ac4ManNAz) pretreatment. Significantly, NP‐DBD exhibits a multifaceted effect encompassing PDT/PTT/NIR‐II FLI upon 808 nm laser irradiation, thereby better activating the cGAS‐STING pathway, culminating in a compelling tumor inhibition effect augmented by robust immune modulation.
Funder
National Natural Science Foundation of China
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science
Cited by
4 articles.
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