Folate-targeted co-delivery polymersomes for efficient photo-chemo-antiangiogenic therapy against breast cancer and in vivo evaluation via OCTA/NIRF dual-modal imaging

Abstract

Intelligent nanoplatform that combines multimodal imaging and therapeutic effects holds great promise for precise and efficient cancer therapy. Herein, folate-targeted polymersomes with stimuli-responsiveness were fabricated and evaluated by near-infrared fluorescence (NIRF) and optical coherence tomography angiography (OCTA) dual-imaging for photo-chemo-antiangiogenic therapy against cancer. The folate-targeted polymersomes (FA-MIT-SIPS) not only integrated ammonium bicarbonate (ABC) and mitoxantrone (MIT) into their hydrophilic cavity but also encapsulated indocyanine green (ICG) and sorafenib (SOR) within their hydrophobic layer. NIRF imaging demonstrated that FA-MIT-SIPS effectively accumulated and retained in the tumors. Upon 808 nm laser irradiation, the ICG produced hyperthermia and reactive oxygen species (ROS) for efficient photothermal and photodynamic therapy. In addition, the decomposition of ABC in responsive to acidic tumor environment and ICG-induced hyperthermia accelerated drug release. The released MIT accumulated in nucleus to inhibit DNA synthesis, while the released SOR destructed tumor vascularization. Notably, OCTA imaging was applied to observe the tumor blood flow upon the combination therapy, demonstrating that FA-MIT-SIPS obviously decreased the vessels area density. Moreover, the synergistic photo-chemo-antiangiogenic therapy of FA-MIT-SIPS achieved excellent antitumor effect with 40% of the 4T1 tumor-bearing mice being completely cured without recurrence. The multifunctional polymersomes provide a promising dual-modal imaging-evaluated synergistic strategy for tumor therapy.