Engineering H₂O₂ and O₂ Self‐Supplying Nanoreactor to Conduct Synergistic Chemiexcited Photodynamic and Calcium‐Overloaded Therapy in Orthotopic Hepatic Tumors

Abstract

Photodynamic therapy (PDT) is traditionally ineffective for deeply embedded tumors due to the poor penetration depth of the excitation light. Chemiluminescence resonance energy transfer (CRET) has emerged as a promising mode of PDT without external light. To date, related research has frequently used endogenous hydrogen peroxide (H 2 O 2 ) and oxygen (O 2 ) inside the solid tumor microenvironment to trigger CRET-mediated PDT. Unfortunately, this significantly restricts treatment efficacy and the development of further biomedical applications because of the limited amounts of endogenous H 2 O 2 and O 2 . Herein, a nanohybrid (mSiO 2 /CaO 2 /CPPO/Ce6: mSCCC) nanoparticle (NP) is designed to achieve synergistic CRET-mediated PDT and calcium (Ca 2+ )-overload-mediated therapy. The calcium peroxide (CaO 2 ) formed inside mesoporous SiO 2 (mSC) with the inclusion of the chemiluminescent agent (CPPO) and photosensitizer (Ce6) self-supplies H 2 O 2 , O 2 , and Ca 2+ allowing for the subsequent treatments. The Ce6 in mSCCC NPs is excited by chemical energy in situ following the supply of H 2 O 2 and O 2 to produce singlet oxygen ( 1 O 2 ). The nanohybrid NPs are coated with stearic acid to avoid decomposition during blood circulation through contact with aqueous environment. This nanohybrid shows promising performance in the generation of 1 O 2 for external light-free PDT and the release of Ca 2+ ions for Ca 2+ -overloaded therapy against orthotopic hepatocellular carcinoma.

Near Infrared-Activatable Methylene Blue Polypeptide Codelivery of the NO Prodrug via π–π Stacking for Cascade Reactive Oxygen Species Amplification-Mediated Photodynamic Therapy

“…Hypoxia in solid tumors was another obstacle that urgently needs to be overcome to improve PDT efficiency. , Many efforts have been made to directly deliver exogenous O 2 to tumors including the use of red blood cells, , perfluorocarbon nanocarriers , and hemoglobin molecules. , These O 2 -delivery strategies have several drawbacks, such as low O 2 -loading content, O 2 leakage during circulation, and burst O 2 release in tumors . Considering that the severe hypoxia in tumors is caused by excessive tumor cell proliferation and respiration consumption of intracellular O 2, inhibiting mitochondrial respiration to economize O 2 may be an innovative strategy to relieve hypoxia in tumors rather than supplying O 2.…”

Inhibition of melanoma using a nanoceria-based prolonged oxygen-generating phototherapy hydrogel

“…However, traditional tumor treatment often confronts obstacles due to visible toxic side effects and drug resistance ( 4 ). Recently, synergetic photodynamic therapy (PDT) has been introduced to overcome melanoma and has shown great potential in the field of tumor therapy ( 5 , 6 ). As a noninvasive technology, PDT addresses spectacular advantages such as high localized tissue damage and minimal side effects ( 7 ).…”

Effective Nanocomposite Based on Bi2MoO6/MoS2/AuNRs for NIR-II Light-Boosted Photodynamic/Chemodynamic Therapy

“…Currently, significant effort has been spent on developing effective cancer treatment methods owing to the high death rate caused by malignant tumors. − Dynamic therapy, which can kill cancer cells by producing reactive oxygen species (ROS) from the original substances in the tumor, is one of the promising cancer treatment methods. Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are common types of dynamic therapy approaches given the different generating mechanisms of ROS. − Compared with conventional cancer treatments (surgery, chemotherapy, and radiotherapy), PDT gains much attention due to its noninvasiveness, low toxicity, and minimal side effect.…”