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Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular
Yang Wang1, Liang Zhang2, Guosheng Zhao3
1Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Background:
No prominent advancements in osteosarcoma (OS) treatment have been made in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, the lack of targeted photosensitizers for OS treatment severely limits its applications.
Results:
In this study, we constructed a potential theranostic nanoplatform by using (poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) encapsulating IR780 into the shell (PLGA-IR780 NPs), which were further camouflaged with human OS cell membranes from the HOS cell line (MH-PLGA-IR780 NPs). These constructed NPs showed the capacity for homologous targeting with excellent photoacoustic (PA)/fluorescence (FL) imaging ability. Benefitting from their homologous targeting capacity, MH-PLGA-IR780 NPs obviously promoted cell endocytosis in vitro and tumor accumulation in vivo, which could further improve PDT performance under near-infrared (NIR) irradiation. In addition, to their homologous targeting and PA/FL dual-mode imaging ability, MH-PLGA-IR780 NPs had advantages in penetrating deeper into tumor tissues and in real-time dynamic distribution monitoring in vivo, which laid a foundation for further clinical applications in OS. Moreover, we demonstrated that PDT guided by the constructed NPs could significantly induce HOS cells apoptosis and ferroptosis via excessive accumulation of reactive oxygen species (ROS), and further determined that the potential anticancer molecular mechanism of apoptosis was triggered by the release of cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and that ferroptosis caused the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and the inactivation of glutathione peroxidase 4 (GPX4), synergistically leading to excessive accumulation of Lipid-ROS and Lipid peroxides (LPOs). Concurrently, MH-PLGA-IR780 NPs-guided PDT also showed an obvious inhibitory effect on tumor growth in vivo.
Conclusion:
These results suggest that this homologous targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and contributes a new and promising approach for OS therapy.
Insights
This study developed a novel theranostic nanoplatform for osteosarcoma (OS) treatment. The platform enhances photodynamic therapy (PDT) efficacy through homologous targeting and dual-mode imaging, offering a promising new approach for OS therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Osteosarcoma (OS) treatment has seen limited progress in two decades.
- Photodynamic therapy (PDT) shows promise but lacks targeted agents for OS.
Purpose of the Study:
- To develop a targeted nanoplatform for improved OS photodynamic therapy.
- To create a theranostic system for imaging and treatment of OS.
Main Methods:
- Constructed poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) encapsulating IR780.
- Camouflaged NPs with human OS cell membranes for homologous targeting (MH-PLGA-IR780 NPs).
- Evaluated NP targeting, imaging (photoacoustic/fluorescence), and PDT efficacy in vitro and in vivo.
Main Results:
- MH-PLGA-IR780 NPs demonstrated homologous targeting, enhanced cellular uptake, and tumor accumulation.
- The nanoplatform enabled effective photoacoustic/fluorescence dual-mode imaging and deeper tumor penetration.
- PDT guided by MH-PLGA-IR780 NPs induced significant apoptosis and ferroptosis in OS cells, inhibiting tumor growth.
Conclusions:
- The homologous targeting-based theranostic nanoplatform effectively improves PDT performance in osteosarcoma.
- This approach offers a novel and promising strategy for osteosarcoma therapy.
