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Engineered MOF-Enzyme Nanocomposites for Tumor Microenvironment-Activated Photodynamic Therapy with Self-Luminescence
Liefeng Hu1,2, Chuxiao Xiong1,2, Jun-Jie Zou1,2
1Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
Abstract:
Photodynamic therapy (PDT) is a promising strategy for cancer treatment. However, its efficiency is hindered by three key parameters, namely, limited penetration depth of external light, tumor hypoxia, and self-aggregation of photosensitizers. Herein, we fabricated a novel "all-in-one" chemiluminescence-PDT nanosystem through the integration of an oxygen-supplying protein (hemoglobin, Hb) and a luminescent donor (luminol, Lum) in hierarchically engineered mesoporous porphyrinic metal-organic framework (MOF) nanoparticles. Mechanistically, the in situ chemiluminescence of Lum is activated by the high concentration of H2O2 in 4T1 cancer cells and further catalyzed by Hb and then absorbed by the porphyrin ligands in MOF nanoparticles through chemiluminescence resonance energy transfer. The excited porphyrins then sensitize oxygen supplied by Hb to produce sufficient reactive oxygen species that kill cancer cells. The MOF-based nanocomposite demonstrates excellent anticancer activity both in vitro and in vivo, with eventually a 68.1% tumor inhibition rate after intravenous injections without external light irradiation. This self-illuminating, oxygen-self-supplying nanosystem integrates all essential components of PDT into one simple nanoplatform, demonstrating great potential for the selective phototherapy of deep-seated cancer.
Insights
This study presents a novel chemiluminescence-photodynamic therapy (PDT) nanosystem that overcomes limitations of traditional PDT. The "all-in-one" system effectively inhibits tumor growth without external light, showing promise for deep-seated cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Photodynamic therapy (PDT) shows promise for cancer treatment but faces challenges including limited light penetration, tumor hypoxia, and photosensitizer aggregation.
- Overcoming these limitations is crucial for enhancing PDT efficacy, especially for deep-seated tumors.
Purpose of the Study:
- To develop an "all-in-one" chemiluminescence-PDT nanosystem integrating oxygen supply and light generation within a single nanoplatform.
- To address the limitations of conventional PDT by creating a self-sufficient system for effective cancer treatment.
Main Methods:
- Fabrication of a hierarchical mesoporous porphyrinic metal-organic framework (MOF) nanoparticle encapsulating hemoglobin (Hb) and luminol (Lum).
- Utilizing in situ chemiluminescence activated by H2O2 in cancer cells, catalyzed by Hb, and transferred to MOF porphyrins via chemiluminescence resonance energy transfer.
- Generating reactive oxygen species (ROS) through excited porphyrins sensitizing Hb-supplied oxygen.
Main Results:
- The MOF-based nanocomposite demonstrated potent in vitro and in vivo anticancer activity.
- Achieved a significant 68.1% tumor inhibition rate after intravenous injection without external light irradiation.
- The nanosystem effectively produced ROS, leading to cancer cell death.
Conclusions:
- The developed chemiluminescence-PDT nanosystem successfully integrates essential PDT components, offering a self-illuminating and oxygen-supplying solution.
- This approach holds significant potential for the selective phototherapy of deep-seated cancers, overcoming key limitations of traditional PDT.
- The study highlights the efficacy of MOF-based nanoplatforms in advancing cancer treatment strategies.
