Synergizing Upconversion Nanophotosensitizers with Hyperbaric Oxygen to Remodel the Extracellular Matrix for Enhanced Photodynamic Cancer Therapy

Abstract

Photodynamic therapy (PDT) holds great promise as a noninvasive and selective cancer therapeutic treatment in preclinical research and clinical practice; however, it has limited efficacy in the ablation of deep-seated tumor because of hypoxia-associated circumstance and poor penetration of photosensitizers to cancer cells away from the blood vessels. To tackle the obstacles, we propose a therapeutic strategy that synergizes upconversion nanophotosensitizers (UNPSs) with hyperbaric oxygen (HBO) to remodel the extracellular matrix for enhanced photodynamic cancer therapy. The UNPSs are designed to have an Nd-sensitized sandwiched structure, wherein the upconversion core serves as light transducers to transfer energy to the neighboring photosensitizers to produce reactive oxygen species (ROS). With HBO, photodynamic process can generate abundant ROS in the intrinsically hypoxic tumor. It is revealed for the first time that HBO-assisted PDT decomposes collagen in the extracellular matrix of tumor and thus facilitates the diffusion of oxygen and penetration of UNPSs into the deeper area of tumor. Such a synergic effect eventually results in a significantly enhanced therapeutic efficacy at a low laser power density as compared with that using UNPSs alone. In view of its good biosafety, the HBO-assisted and UNPSs-mediated PDT provides new possibilities for treatment of solid tumors.

The role of collagen in cancer: from bench to bedside

“…Nitric oxide activated endogenous MMP-1 and MMP-2 to deplete collagen, and it significantly improved anticancer efficacy while exerting no overt toxicity in animal models [213]. Under hypoxic cancer conditions, hyperbaric oxygen therapy decreased collagen deposition to enhance chemotherapy efficacy and photodynamic upconversion nanophotosensitizer cancer therapy [214].…”

Recent advances in the synthesis and application of Yb-based fluoride upconversion nanoparticles

“…3d). 57 The UCNP@mSiO 2 design is versatile for loading various kinds of therapeutic agents. In addition to photosensitizers, chemotherapy drugs have also been successfully installed in the nanocomposites.…”

Fighting Hypoxia to Improve PDT

“…Similar results as previously were obtained using carbogen and HBO conditions. Li et al [26] used also hyperbaric conditions with upconversion nanoparticles (UCNPs). They synthesized a core@shell NPs NaGdF 4 :Yb,Er,Ca@NaYbF 4 :Ca, with an upconversion core which can transfer its energy to Rose Bengal, and produce ROS under 808 nm laser excitation ( Figure 1).…”

“…Schematic illustration for the synthesis of NaGdF4:Yb,Er,Ca@NaYbF4:Ca@NaNdF4:Gd,Ca @mSiO2 NPs. Reprinted from [26] with permission from the American Chemical Society, Copyright 2018.…”