O₂‑Loaded pH-Responsive Multifunctional Nanodrug Carrier for Overcoming Hypoxia and Highly Efficient Chemo-Photodynamic Cancer Therapy

Tumor therapy is facing great challenges in improving drug efficiency while reducing side effects. Herein, a novel multifunctional nanodrug carrier UC@mSiO2-RB@ZIF-O2-DOX-PEGFA (URODF) that combines oxygen (O2)-enhanced photodynamic therapy (PDT) with pH-responsive chemotherapy is presented. Eight hundred eight nanometer NIR light-irradiated NaYF4:Yb/Er@NaYbF4:Nd@NaGdF4 nanoparticles (UC) were employed as both upconversion/magnetic resonance imaging matrix and motivator for photosensitizer in PDT with deep penetration depth. Mesoporous silica shell (mSiO2) was used as the carrier for photosensitizer Rose Bengal (RB). Zeolitic imidazolate framework-90 (ZIF-90) was coated outside of mSiO2 as O2 reservoir to quickly release O2 in tumor microenvironment and alleviate tumor hypoxia for enhanced PDT. Doxorubicin (DOX) and NH2-poly­(ethylene glycol) modified folic acid (PEGFA) were covalently conjugated on the surface of nanoparticles for synergetic therapy. The drug-loading capacity reaches 5.6 and 6.0% for RB and DOX, respectively. In vitro and in vivo experiments demonstrate great therapeutic effect of URODF. This work presents for the first time a multifunctional nanodrug carrier that combines upconversion nanoparticles with metal–organic framework structure for O2-loaded combination therapy, which might open a promising way of enhancing tumor therapeutic efficacy