Oxygen generating nanoparticles for improved photodynamic therapy of hypoxic tumours

Abstract

Photodynamic therapy (PDT) is a clinically approved anti-cancer treatment that involves the activation of an otherwise inactive sensitiser drug with light, which in the presence of molecular oxygen, generates cytotoxic reactive oxygen species (ROS). As oxygen is a key requirement for the generation of ROS in PDT and given the fact that hypoxia is a characteristic of most solid cancerous tumours, treating hypoxic tumours using PDT can be a challenge. In this manuscript, we have prepared a CaO nanoparticle (NP) formulation coated with a pH-sensitive polymer to enable the controlled generation of molecular oxygen as a function of pH. The polymer coat was designed to protect the particles from decomposition while in circulation but enable their activation at lower pH values in hypoxic regions of solid tumours. The oxygen generating capability of the polymer coated NPs was demonstrated in aqueous solution with minimal oxygen produced at pH7.4, whereas it increased significantly when the pH was reduced to 6.2. The polymer coated CaO NPs were also observed to significantly increase tumour pO levels (p<0.05) in mice bearing ectopic human xenograft MIA PaCa-2 pancreatic tumours with an average increase in tumour pO of 6.5mmHg in the period 10-30min following administration. A statistically significant improvement in PDT mediated efficacy (p<0.001) was also observed when the particles were administered to mice bearing the same tumours 20min prior to PDT treatment. These results suggest that the polymer coated CaO NP formulation offers significant potential as an in situ method for oxygen generation to enhance the efficacy of treatments that depend on the presence of oxygen to elicit a cytotoxic effect.

An open source and reduce expenditure ROS generation strategy for chemodynamic/photodynamic synergistic therapy

“…The MSNs with an average diameter of 120 nm were synthesized by a hydrothermal method ( Supplementary Figure 1a). The CaO 2 NPs with an average diameter of 20 nm were prepared through a hydrolysis-precipitation process (Supplementary Figure 1b) 33,34 . Then, the CaO 2 NPs were assembled onto the surface of MSNs to form MSNs@CaO 2 NPs in methanol through electrostatic adsorption, confirmed by the transmission electron microscope (TEM) images ( Fig.…”

“…Synthesis of (MSNs@CaO 2 -ICG)@LA. The CaO 2 nanoparticles were synthesized according to previous literature 34 . In brief, ultrapure water (3 mL), calcium chloride (2.7 mmol), ammonia solution (1.5 mL, 1 M) and PEG400 (12 mL) were successively added in the round bottom flask under stirring.…”

Self‐Supply of O2 and H2O2 by a Nanocatalytic Medicine to Enhance Combined Chemo/Chemodynamic Therapy

“…Owing to its high biocompatibility and efficient O 2 ‐evolving ability, calcium peroxide (CaO 2 ) has previously been utilized as an O 2 production material (Equation ) for improving PDT efficiency and overcoming the hypoxia‐induced DOX resistance in solid tumors . Moreover, CaO 2 can dissolve in water to form H 2 O 2 under acidic conditions (Equation ) .…”

Nanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment

“…85 Another effective strategy that is gaining increasing attention is the use of upconversion (UC) nanomaterials, which can convert long-wavelength light excitation into multiple short-wavelength emissions. [96][97][98] However, numerous persisting problems, such as potential toxicity, non-selectivity, low oxygen carrying capacity and poor delivery efficiency, cannot be ignored. 86 Gulzar et al designed graphene oxide as a carrier with chlorin e6 loading under 808 nm NIR laser excitation for imagingguided PDT.…”

“…For example, perfluorocarbon, CaO 2 and carbon nitride (C 3 N 4 ) have been constructed as nanoparticles for PDT. [96][97][98] However, numerous persisting problems, such as potential toxicity, non-selectivity, low oxygen carrying capacity and poor delivery efficiency, cannot be ignored.…”