Oxygen-Generating Hydrogels Overcome Tumor Hypoxia to Enhance Photodynamic/Gas Synergistic Therapy

Abstract

Hypoxic environment is a bottleneck of photodynamic therapy (PDT) in tumor treatment, as oxygen is the critical substrate for photosensitivity reaction. Herein, a sustained oxygen supply system based on cerium nanoparticles and hydrogel (GHCAC) was explored for enhanced synergistic PDT and gas therapy. Ceria nanoparticles were prepared as a drug carrier by self-assembly mediated by hyaluronic acid (HA), a targeting for CD44 on cervical cancer cells, followed by photosensitizer and l-arginine (l-Arg) loading. Then, the GHCAC system was developed by incorporating a prepared nanocarrier (HCePA) and O2-evolving agent calcium peroxide (CaO2) into the hydrogel (Gel) developed by a poloxamer. Gel in the system could moderately infiltrate H2O to react with CaO2 and generate sustained oxygen using the catalase-like activity of HCePA. The system could efficiently alleviate hypoxia in tumor environments for up to 7 days, meeting the “once injection, repeat irradiation” strategy and enhanced PDT efficacy. Besides, the generated singlet oxygen (1O2) in the PDT process could also oxidize l-Arg into high concentrations of nitric oxide for synergistic gas therapy. The developed oxygen supplied and drug delivery Gel system is a new strategy for synergistic PDT/gas therapy to overcome cervical cancer.

Low‐Cost, High‐Pressure‐Synthesized Oxygen‐Entrapping Materials to Improve Treatment of Solid Tumors

“…Water-splitting nanoparticles 0.0015 x [27] O 2 carrying hydrogels w/radiotherapy 0.095 x [28] O 2 -generating hydrogels 0.004 12 [29] pH sensitive O 2 nanobubbles 0.0049 27 [30] RBC O 2 delivering microvehicles 0.0013 x [31] O 2 encapsulating polydopamine nanoparticles 0.0069 19.7 [32] Cyanobacteria O 2 pump 0.0084 x [33] same in all three (Figure 2B), and each material entrapped twice as much oxygen as previously studied materials (Table 1). [8,[24][25][26][27][28][29][30][31][32][33] In addition, the density of the foam O 2 -GeMs was significantly lower than those of hydrogel and solid O 2 -GeMs (Figure S5, Supporting Information).…”

Calcium-peroxide-mediated cascades of oxygen production and glutathione consumption induced efficient photodynamic and photothermal synergistic therapy

“…Li et al developed an injectable thermosensitive gel system (GHCAC), which used CaO 2 to generate oxygen. 29 Zhang et al prepared LipoMB/CaO 2 nanoparticles, which could realize O 2 self-sufficiency. 30 Under acidic conditions, CaO 2 reacts with water and produces O 2 , improving hypoxia in tumors.…”

Precision gas therapy by ultrasound‐triggered for anticancer therapeutics

“…As is well knowledge, a variety of gaseous molecules including nitric oxide (NO), 23 oxygen (O 2 ), 24 hydrogen sulfide (H 2 S), 25 hydrogen (H 2 ), 26 and carbon monoxide (CO) 27 play a crucial role in many biological processes. Particularly, these molecules act as messengers that can cause specific physiologic or biochemical alteriations in cells, tissues, or organisms 28 .…”