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Updated: Sep 24, 2025
Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Nanoengineering a metal-organic framework for osteosarcoma chemo-immunotherapy by modulating
Qingxin Fan1,2,3, Jing Zuo1,2, Hailong Tian1,2
1Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region (Hospital.C.T.), Sichuan University, Chengdu, 610041, China.
Background:
The high postoperative recurrence rate and refractoriness of relapsed tumors are still a conundrum for the clinical management of osteosarcoma (OS). New therapeutic options are urgently needed. Depriving the nourishment of myeloid-derived suppressor cells is a novel strategy to improve the immunosuppressive tumor microenvironment for enhanced OS therapy.
Methods:
We synthesized a hyaluronic acid (HA)-modified metal-organic framework for combinational chemotherapy and immunotherapy of OS. Zeolitic Imidazolate Framework-8 (ZIF-8) was prepared by a one-pot synthetic method, Gemcitabine (Gem) and D-1-Methyltryptophan (D-1-MT) were loaded into the ZIF-8 during the synthesis process to make ZIF-8@Gem/D-1-MT nanoparticles (NPs). The end product (HA/ZIF-8@Gem/D-1-MT NPs) was obtained by HA modification on the surface of ZIF-8@Gem/D-1-MT NPs. The obtained HA/ZIF-8@Gem/D-1-MT NPs have excellent potential as a drug delivery vector for chemotherapy and immunotherapy in vitro and vivo.
Results:
The results indicate that HA/ZIF-8@Gem/D-1-MT NPs were readily taken up by OS cells, and that the Gem and D-1-MT were effectively released into the acidic environment. The HA/ZIF-8@Gem/D-1-MT NPs could efficiently decrease OS cell viability (proliferation, apoptosis, cell cycle, migration and invasion). And HA/ZIF-8@Gem/D-1-MT NPs could reactivate antitumor immunity by inhibiting indoleamine 2,3 dioxygenase and myeloid-derived suppressor cells. Furthermore, animal experiments confirmed that HA/ZIF-8@Gem/D-1-MT NPs could induce intratumoral immune responses and inhibit tumor growth. Additionally, HA/ZIF-8@Gem/D-1-MT NPs have a good safety profile.
Conclusions:
Our findings demonstrate that the combination of Gem with D-1-MT brings new hope for the improved treatment of OS, while the generation of the nanosystem has increased the application potential and flexibility of this strategy.
Insights
This study developed novel nanoparticles combining chemotherapy and immunotherapy to treat osteosarcoma (OS). The new treatment effectively reduced OS tumors and improved antitumor immunity with a good safety profile.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Osteosarcoma (OS) presents challenges due to high recurrence rates and treatment resistance.
- Novel therapeutic strategies are crucial for improving OS management.
- Targeting myeloid-derived suppressor cells offers a new approach to enhance OS therapy by modulating the tumor microenvironment.
Purpose of the Study:
- To develop a hyaluronic acid (HA)-modified metal-organic framework (MOF) for combined chemotherapy and immunotherapy of OS.
- To create nanoparticles (NPs) loaded with Gemcitabine (Gem) and D-1-Methyltryptophan (D-1-MT) for enhanced OS treatment.
Main Methods:
- Synthesized Zeolitic Imidazolate Framework-8 (ZIF-8) nanoparticles loaded with Gemcitabine and D-1-Methyltryptophan.
- Modified ZIF-8@Gem/D-1-MT NPs with hyaluronic acid to create HA/ZIF-8@Gem/D-1-MT NPs.
- Evaluated the efficacy and safety of the developed NPs in vitro and in vivo for OS treatment.
Main Results:
- HA/ZIF-8@Gem/D-1-MT NPs demonstrated efficient cellular uptake and drug release in acidic environments.
- NPs significantly reduced OS cell viability, proliferation, migration, and invasion while inducing apoptosis.
- The treatment reactivated antitumor immunity by inhibiting indoleamine 2,3 dioxygenase and myeloid-derived suppressor cells, leading to tumor growth inhibition in vivo.
- The developed NPs exhibited a favorable safety profile.
Conclusions:
- The combination of Gemcitabine and D-1-Methyltryptophan shows promise for improved osteosarcoma treatment.
- The developed nanosystem enhances the application potential and flexibility of this combined therapeutic strategy.
