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Nanoparticles armed with chemotherapy drug and fluorescence probe have become an effective anticancer strategy for their advantages in cancer diagnosis and treatment. However, fluorophore for diagnostic medicine with deep penetration depth and high resolution are still very rare, while rational designs are also required to improve the tumor retention and target-site drug delivery. Herein, a two-photon fluorophore with aggregation-induced emission and large two-photon absorption cross-section has been designed for two-photon bioimaging, and a novel theranostic nanoplatform is also constructed based on doxorubicin and the two-photon fluorophore conjugated copolymer, P(TPMA-co-AEMA)- PEI(DA)-Blink-PEG (PAEEBlink-DA). The micelles maintain a "stealth" property during blood circulation and is activated in the acidic tumor microenvironment, which triggers the charge-conversion and results in enhanced micellar internalization. Meanwhile, PAEMA chains can convert from hydrophobicity to hydrophilicity with accelerated drug release and particle size expansion. The enlarged particle size would potentially extend the retention time of these micelles. Moreover, a great AIE active two-photon bioimaging with tissue penetration depth up to 150 μm is observed and the in vivo biodistribution of nanoparticles can be traced. The in vivo antitumor results further indicate the obvious reduction of adverse effect and enhanced treatment effect of these micelles, proving that these PAEEBlink-DA micelles would be a potential candidate for tumor theranostic applications.
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