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Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
An "Outer Piezoelectric and Inner Epigenetic" Logic-Gated PANoptosis for Osteosarcoma Sono-Immunotherapy and Bone
Xiaoting Wang1, Xun Guo1, Hongze Ren2
1Ultrasound Department of the Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, 400010, P. R. China.
Abstract:
The precise manipulation of PANoptosis, a newly defined cell death pathway encompassing pyroptosis, apoptosis, and necroptosis, is highly desired to achieve safer cancer immunotherapy with tumor-specific inflammatory responses and minimal side effects. Nonetheless, this objective remains a formidable challenge. Herein, an "AND" logic-gated strategy for accurately localized PANoptosis activation, utilizing composite 3D-printed bioactive glasses scaffolds integrated with epigenetic regulator-loaded porous piezoelectric SrTiO3 nanoparticles is proposed. The "logic-gated" strategy is co-programmed by an "outer" input signal of exogenous ultrasound irradiation to produce reactive oxygen species and an "inner" input signal of acid tumor microenvironment to ensure the epigenetic demethylation regulation, guaranteeing the tumor-specific PANoptosis. Specifically, immunogenic PANoptosis triggers dendritic cell maturation and cytotoxic T cell activation, amplifying antitumor immune responses and significantly suppressing osteosarcoma growth, with a suppression rate of ≈73.47 ± 5.2%. In addition, the well-known bioactivities of Sr-doped scaffolds expedite osteogenic differentiation and reinforce bone regeneration. Therefore, this work provides a paradigm of logic-gated sono-piezoelectric biomaterial platform with concurrently exogenous/endogenous activated PANoptosis for controlled sono-immunotherapy of osteosarcoma, and related bone defects repair.
Insights
This study introduces a novel biomaterial platform for precise PANoptosis activation in cancer immunotherapy. This approach enhances anti-tumor immunity and bone repair, offering a safer treatment for osteosarcoma.
Area of Science:
- Biomaterials Science
- Immunotherapy
- Nanotechnology
Background:
- PANoptosis, a cell death pathway, offers potential for targeted cancer immunotherapy.
- Current challenges include achieving tumor-specific activation and minimizing side effects.
- Developing localized and controlled cell death induction is crucial for effective cancer treatment.
Purpose of the Study:
- To develop a logic-gated biomaterial platform for precise PANoptosis activation.
- To investigate the co-programmed activation by ultrasound and tumor microenvironment.
- To evaluate the efficacy of this platform in osteosarcoma immunotherapy and bone regeneration.
Main Methods:
- Fabrication of 3D-printed bioactive glass scaffolds with SrTiO3 nanoparticles.
- Loading nanoparticles with epigenetic regulators.
- Utilizing an "AND" logic-gated strategy activated by ultrasound and tumor acidity.
- Assessing PANoptosis induction, immune cell activation, and anti-tumor effects in osteosarcoma models.
- Evaluating bone regeneration capabilities of the scaffolds.
Main Results:
- The proposed platform achieved tumor-specific PANoptosis activation.
- Ultrasound and acidic tumor microenvironment co-programmed the "AND" logic gate.
- Immunogenic PANoptosis enhanced dendritic cell maturation and T cell activation.
- Significant suppression of osteosarcoma growth (≈73.47%) was observed.
- The scaffolds promoted osteogenic differentiation and bone regeneration.
Conclusions:
- A novel logic-gated sono-piezoelectric biomaterial platform for controlled PANoptosis was developed.
- This platform enables targeted sono-immunotherapy for osteosarcoma.
- The approach concurrently addresses cancer treatment and bone defect repair.
