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A Protein-Polymer Bioconjugate-Coated Upconversion Nanosystem for Simultaneous Tumor Cell Imaging, Photodynamic Therapy, and Chemotherapy.

Combined cancer therapy possesses many advantages including improved tumoricidal efficacy, reduced side effects, and retarded drug resistance. Herein, a protein-polymer bioconjugate-coated multifunctional upconversion nanosystem, consisting of upconversion nanoparticles (UCNs) core, tailored amphiphilic protein-polymer bioconjugate shell, and photosensitizer zinc phthalocyanine (ZnPc) and antitumor drug doxorubicin coloaded inside, was elaborately developed for combined photodynamic therapy (PDT) and chemotherapy. In this system, UCNs core could convert deep penetrating near-infrared light to visible light for simultaneous cell fluorescence imaging and photodynamic therapy by activating ZnPc to generate cytotoxic ROS, while the protective shell of bovine serum albumin-poly(ε-caprolactone) (BSA-PCL) offered excellent water solubility, good stability, and low cytotoxicity. The ROS production test showed that this nanosystem could successfully generate singlet oxygen under NIR irradiation. A cellular uptake study demonstrated that intense fluorescence emission of the UCNs could be observed in HeLa cells, indicating their outstanding real-time imaging capability. More importantly, compared with single PDT or chemotherapy systems, the constructed combined therapy UCNs system demonstrated significantly enhanced tumor cell killing efficiency. On the basis of our findings, this multifunctional UCNs nanosystem could be a promising versatile theranostic nanoplatform for image-guided combined cancer therapy.