Combining Photodynamic Therapy and Targeted Drug Delivery Systems: Enhancing Mitochondrial Toxicity for Improved Cancer Outcomes
Abstract
:1. Introduction
2. Photodynamic Therapy
2.1. The Mechanism of Photodynamic Therapy
2.2. Photosensitizers
Types of Photosensitizers
2.3. Light Source
2.4. Drawbacks of PDT
2.5. Challenges in PDT Treatment
3. Targeted Drug Delivery Systems
3.1. Drug Delivery in Cancer Targets Mitochondria
3.2. Drug Targeting Mitochondrial DNA
3.3. Mitochondrial Delivery by Nanoparticles
3.4. Mitochondrial Delivery by Lipid-Based Nanocarriers
3.5. Mitochondrial Delivery by Peptides
3.6. Challenges in Mitochondrial Drug Targeting
4. Drug-Induced Mitochondrial Toxicity
4.1. Mitochondria-Independent Chemotherapeutics
4.2. Effects of PDT on the Mitochondrial Membrane Potential
5. Mitochondria as a Potential Cancer Therapeutic Target
5.1. Apoptosis Regulation
5.2. Metabolic Rewiring
5.3. Therapeutic Strategies
6. Mitochondrial Drug Delivery Mechanisms in Cancer
6.1. Photodynamic Therapy-Induced Mitochondrial Toxicity
6.1.1. Apoptosis
6.1.2. Autophagy
6.2. Nanoparticle-Based Delivery Mechanisms in Cancer
7. Clinical Developments in PDT and Mitochondria Targeting in Cancer
8. Preclinical Studies: Cellular Assays and Animal Models
9. Conclusions and Future Perspectives
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Drug | Type of Cancer | Model | Mitochondria Function | Mechanism of Action | References |
---|---|---|---|---|---|
Metformin | Breast, prostate, melanoma, ovary, and lung | Clinical trials | Bioenergetic | Inhibition complex I | [86,87] |
Vitamin K3 | Ovary | Clinical trials | Signaling | Increasing generation of ROS | [90] |
Mipsagargin (G-202) | Glioblastoma and liver | Clinical trials | Signaling | Mitochondrial Ca2+ transfer modulation | [92] |
BAY 87-2243 | Lung and prostate | Clinical trials | Bioenergetic | Inhibition complex I | [93] |
IACS-010,759 | Acute myeloid leukemia and chronic lymphocytic leukemia | Clinical trials | Bioenergetic | Inhibition complex I | [94] |
MitoVES | Breast | Preclinical | Bioenergetic | Inhibition complex I and II | [95] |
Lonidamine | Lung | Clinical trials | Bioenergetic | Inhibition complex II | [96] |
Venetoclax and WEHI-539 | Breast | Preclinical | Bioenergetic | Reducing bioenergetic | [97] |
VLX600 | Colon | Clinical trials | Bioenergetic | ETC inhibitor | [98] |
Gamitrinib | Lung and prostate | Preclinical | Bioenergetic | Inhibition HSP90 and TRAP-1 activity | [99] |
CPI-613 | Pancreas and hematological cancers | Clinical trials | Bioenergetic | PDH and α-KGDH inhibitor | [100,101] |
Enasidenib and Ivosidenib | Acute myeloid leukemia | Clinical trials | Bioenergetic | Mutant IDH inhibitors | [102] |
Dichloroacetate | Lung and liver | Clinical trials | Bioenergetic | PDKs inhibitor | |
Gossypol | Breast, brain, and prostate | Clinical trials | Bioenergetic | LDHA inhibitor and NADH competitor | [103] |
Tioconazole | Colon | Clinical trials | Signaling | Blocking autophagy targeting ATG4B | [104] |
Verteporfin | Pancreas | Clinical trials | Signaling | Blocking autophagosome formation | [105] |
Mitoxantrone and pixantrone | B-cell non-Hodgkin’s lymphoma | Clinical trials | Signaling | MCU complex inhibition | [106] |
GLS inhibitors | Breast and Burkitt lymphoma | Clinical trials | Biosynthesis | Reducing glutamine catabolism | [107,108] |
Experimental Condition | Therapeutic Agent | Treatment Method | Reference |
---|---|---|---|
Ovarian cancer | Paclitaxel-NPs | Chemotherapy | [45] |
Ovarian cancer | Cisplatin-based peptide delivery | Chemotherapy | [46] |
Several cancers | PEGylated-NPs | Drug solubility | [47] |
Cancer therapy | ROS-sensitive NPs | Intracellular release | [50] |
Mitochondrial disorders | Mitochondrial transcription factors | Gene therapy | [55] |
Neurodegenerative diseases | Antioxidant-NPs | Oxidative stress reduction | [56] |
Gene therapy | Oligonucleotide-NPs | Nucleic acid delivery | [57] |
Neurodegenerative diseases | Curcumin-NPs | Antioxidant therapy | [61] |
Cardioprotection | Mitochondria-targeted Peptides | Cellular uptake | [62] |
Mitochondrial diseases | Mitochondrial proteins | Mitochondrial dynamics | [118] |
Breast cancer | Doxorubicin-NPs | Chemotherapy | [153] |
Solid tumors | Antibody-NP complexes | Targeted therapy | [154] |
Cancer treatment | Mitochondria-targeted aptamers | Targeted therapy | [155] |
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Merlin, J.P.J.; Crous, A.; Abrahamse, H. Combining Photodynamic Therapy and Targeted Drug Delivery Systems: Enhancing Mitochondrial Toxicity for Improved Cancer Outcomes. Int. J. Mol. Sci. 2024, 25, 10796. https://doi.org/10.3390/ijms251910796
Merlin JPJ, Crous A, Abrahamse H. Combining Photodynamic Therapy and Targeted Drug Delivery Systems: Enhancing Mitochondrial Toxicity for Improved Cancer Outcomes. International Journal of Molecular Sciences. 2024; 25(19):10796. https://doi.org/10.3390/ijms251910796
Chicago/Turabian StyleMerlin, J. P. Jose, Anine Crous, and Heidi Abrahamse. 2024. "Combining Photodynamic Therapy and Targeted Drug Delivery Systems: Enhancing Mitochondrial Toxicity for Improved Cancer Outcomes" International Journal of Molecular Sciences 25, no. 19: 10796. https://doi.org/10.3390/ijms251910796