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Synergistic Ultrasound-Activable Artificial Enzyme and Precision Gene Therapy to Suppress Redox Homeostasis and Malignant Phenotypes for Controllably Combacting Hepatocellular Carcinoma

ABSTRACT: Hepatocellular carcinoma (HCC) remains one of the most lethal malignant tumors. Multi-modal therapeutics for HCC have attracted increasing attention. However, designing a nanotherapeutic platform with effective chem-/sono- double-modal HCC therapies is still challenging. Here, we first designed a novel porphyrin-based nanomase (Porzyme) P-Por-Os with nano-sonosensitivity for HCC therapy. Endowed with a large hollow spherical structure of poly porphyrins, which efficiently improved the electron transport capacity of polyporphyrins and exposed the active site of superficial metal atoms, P-Por-Os effectively catalyzed the production of ROS from H2O2. This so-called Chemodynamic Therapy (CDT) was further significantly reinforced by Sonodynamic Therapy (SDT) and achieving this therapeutic ultrasound-controlled anti-tumor effects in HCC. More importantly, we developed an metallothionein-2A (MT2A)-targeted enhancement to reverse the resistance to ROS and suppress cancer progression, which could theoretically be termed Precision Gene Therapy (PGT). Overall, the new therapeutic schedule with the triple-combination of P-Por-Os-based CDT, SDT, and PGT achieved remarkable anti-HCC effectiveness. This study reported an innovative artificial enzyme P-Por-Os with high tumor-killing activity and proposed a new triple-combination with CDT, SDT and PGT treatment strategy for HCC.

ORGANISM(S): Mus musculus

PROVIDER: GSE273283 | GEO | 2026/07/26

REPOSITORIES: GEO

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