Fluoride‐Ortho Ester Dimer‐Based pH‐Sensitive Nanoparticles for Oxygen Delivery and Enhanced Photodynamic Therapy

Abstract

Hypoxia is one of the major factors that affect the efficiency of photodynamic therapy (PDT). However, the strategy of using nano‐oxygen carriers to reverse tumor hypoxia still has some drawbacks, which limit its clinical application and translation. Herein, it is reported a method for preparing pH‐sensitive nano‐oxygen carrier for reversing tumor hypoxia and enhancing the efficiency of PDT. Briefly, perfluorocarbons (PFC) with different chain‐lengths (7F or 15F) are linked by acid‐labile ortho ester bonds, then further self‐assembled with Chlorin e6 to form two pH‐sensitive nanodrugs. In vitro tests demonstrate that these nanodrugs possessed good physicochemical properties, including high stability, anti‐adsorption capability, and high oxygen‐loading capacity (24.5 mg L−1). In vivo studies reveal that this system can remarkably alleviate tumor hypoxia and inhibit tumor growth, and 15F@OE dimer particles display the highest antitumor efficiency (84.2%). Overall, this study presents a simple and efficient strategy to deliver oxygen and drugs to tumor tissue, thereby overcoming the limitation of hypoxia‐mediated PDT in cancer treatment.

Research Progress in Oxygen Carrier Design and Application

“…105 The nano-PFC oxygen carrier can also design a pH-responsive PFC oxygen carrier according to the acidic environment inside the tumor, and the tumor inhibition rate reaches 84.2%. 106 PFC oxygen carriers can also enhance the photothermal therapy (PPT) of tumors. When NIR-II light is irradiated, oxygen can be released explosively and simultaneously release the chemotherapy drug doxorubicin, realizing the synergistic antitumor effect of chemotherapy and PPT.…”

“…In addition, perfluorocarbons can dissolve oxygen and retain the oxygen produced by catalase decomposing H 2 O 2 inside the tumor in perfluorocarbons to achieve synergistic PDT . The nano-PFC oxygen carrier can also design a pH-responsive PFC oxygen carrier according to the acidic environment inside the tumor, and the tumor inhibition rate reaches 84.2% . PFC oxygen carriers can also enhance the photothermal therapy (PPT) of tumors.…”

Nanotechnology‐mediated photodynamic therapy: Focus on overcoming tumor hypoxia

“…Oxygen nanocarriers are naturally made of biocompatible materials with a high affinity for oxygen. The most commonly‐used oxygen nanocarriers include perfluorocarbons (PFCs) (Hou et al, 2022; Krafft, 2020), hemoglobin (Hb) (Yang et al, 2018), and metal–organic frameworks (MOF) (Xie et al, 2018). PFCs are oxygen carriers approved by FDA with promising evidence that supports their effectiveness in mitigating hypoxia.…”