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

Abstract

Tumor therapy is facing great challenges in improving drug efficiency while reducing side effects. Herein, a novel multifunctional nanodrug carrier UC@mSiO 2 -RB@ZIF-O 2 -DOX-PEGFA (URODF) that combines oxygen (O 2 )enhanced photodynamic therapy (PDT) with pH-responsive chemotherapy is presented. Eight hundred eight nanometer NIR light-irradiated NaYF 4 :Yb/Er@NaYbF 4 :Nd@NaGdF 4 nanoparticles (UC) were employed as both upconversion/ magnetic resonance imaging matrix and motivator for photosensitizer in PDT with deep penetration depth. Mesoporous silica shell (mSiO 2 ) was used as the carrier for photosensitizer Rose Bengal (RB). Zeolitic imidazolate framework-90 (ZIF-90) was coated outside of mSiO 2 as O 2 reservoir to quickly release O 2 in tumor microenvironment and alleviate tumor hypoxia for enhanced PDT. Doxorubicin (DOX) and NH 2 -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 O 2 -loaded combination therapy, which might open a promising way of enhancing tumor therapeutic efficacy.

A Novel Pt–TiO2 Heterostructure with Oxygen‐Deficient Layer as Bilaterally Enhanced Sonosensitizer for Synergistic Chemo‐Sonodynamic Cancer Therapy

“…To address the problem, many strategies have been developed. For example, perfluorocarbon NPs,17 hemoglobin,18 and metal–organic frameworks19 were used as the carriers to transfer O 2 directly to tumor. Besides, in situ generating of O 2 inside the tumor with enzyme‐based catalysts such as natural enzymes (catalase) and nanozymes (MnO 2 and Pt) has also been explored to relieve hypoxia in tumor microenvironment 14,20.…”

Pressure-induced amorphous zeolitic imidazole frameworks with reduced toxicity and increased tumor accumulation improves therapeutic efficacy In vivo

“…The high drug loading, stability during blood circulation, and pH-responsive drug release in tumor expand their application in cancer therapy [ 10 ]. For instance, ZIF-8 could deliver small molecules, nanoparticles [ 11 ], and enzymes [ 12 , 13 ] to tumor sites and release guests because of the decreased pH of tumor environment [ 14 ]. ZIF-8 has also been widely used in tumor imaging and therapy [ 15 ] as an ideal vehicle.…”

Fighting Hypoxia to Improve PDT

“…Xie et al [169] developed a novel O 2 -loaded pH-responsive multifunctional nanodrug carrier UC@mSiO 2 -RB@ZIF-O2-DOX-PEGFA (URODF) for an improved chemo-PDT efficiency. NaYF 4 :Yb/Er@NaYbF 4 :Nd@NaGdF 4 NPs (UC) were employed for dual-modal upconversion/MR imaging.…”