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pH‐Responsive PEG–Doxorubicin‐Encapsulated Aza‐BODIPY Nanotheranostic Agent for Imaging‐Guided Synergistic Cancer Therapy

Synergistic cancer therapy is of great interest for multiple advantages, such as excellent targeting accuracy, low side effects, and enhanced therapeutic efficiency. Herein, a near‐infrared photosensitizer aza‐BODIPY (AB) with high singlet oxygen quantum yield (ΦΔ = 82%) is designed and synthesized. With Schiff's base obtained from condensation reaction between doxorubicin (DOX) and polyethylene glycol‐benzaldehyde (PEG–CHO) as the polymer matrix, aza‐BODIPY is encapsulated to afford hydrophilic nanoparticles (DAB NPs). The DAB NPs exhibit high reactive oxygen species (ROS) generation rate and outstanding photothermal conversion efficiency (η = 38.3%) under irradiation. In vivo fluorescence‐ and photothermal‐imaging (PTI) results demonstrate that DAB NPs can specifically accumulate at tumor sites and serve as dual‐modal imaging probe for cancer diagnosis. Particularly, triggered by acidic tumor microenvironment, the HCN bond of Schiff's base would be broken simultaneously, resulting in the efficient release of DOX from DAB NPs at tumor sites as well as enhancing the targeting performance of chemotherapeutics. Compared with free DOX and aza‐BODIPY nanoparticles, DAB NPs can inhibit tumor growth more effectively through pH‐responsive photodynamic/photothermal/chemo synergistic therapy. This report may also present a practicable strategy to develop a pH‐responsive nanotheranostic agent for tumor targeting, imaging, and therapy.