1. In situ thermosensitive H 2 O 2 /NO self-sufficient hydrogel for photothermal ferroptosis of triple-negative breast cancer.
- Author
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Sankaranarayanan SA, Eswar K, Srivastava R, Thanekar AM, Gubige M, Bantal V, and Rengan AK
- Subjects
- Animals, Mice, Cell Line, Tumor, Female, Humans, Arginine chemistry, Peroxides chemistry, Peroxides pharmacology, Mice, Inbred BALB C, Photothermal Therapy, Tumor Microenvironment drug effects, Reactive Oxygen Species metabolism, Ferroptosis drug effects, Hydrogen Peroxide chemistry, Hydrogen Peroxide metabolism, Hydrogels chemistry, Hydrogels pharmacology, Nitric Oxide metabolism, Nitric Oxide chemistry, Triple Negative Breast Neoplasms pathology, Triple Negative Breast Neoplasms metabolism, Triple Negative Breast Neoplasms drug therapy, Nanoparticles chemistry
- Abstract
L-Arginine (LA), a semi-essential amino acid in the human body, holds significant potential in cancer therapy due to its ability to generate nitric oxide (NO) continuously in the presence of inducible NO synthase (iNOS) or reactive oxygen species (ROS). However, the efficiency of NO production in tumor tissue is severely constrained by the hypoxic and H
2 O2 -deficient tumor microenvironment (TME). To address this issue, we have developed calcium peroxide (CaO2 ) nanoparticles capable of supplying O2 /H2 O2 , which encapsulate and oxidize an LA-modified lipid bilayer to enable controlled localized NO generation in the presence of ROS, synergising with a ferroptosis inducer, RSL-3 (CPIR NPs). The synthesized nanoparticles were tested in vitro for their anticancer activity in 4T1 cells. To address challenges related to specificity and frequent dosing, we developed an in situ thermosensitive injectable hydrogel incorporating CPIR nanoparticles. Cross-linking at 60 °C creates a self-sufficient formulation, releasing NO/H2 O2 to combat tumor hypoxia. RSL-3 induces ferroptosis, contributing to a synergistic photothermal effect and eliminating tumor in vivo .- Published
- 2024
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