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Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy
- Source :
- Theranostics
- Publication Year :
- 2021
- Publisher :
- Ivyspring International Publisher, 2021.
-
Abstract
- Photodynamic therapy (PDT) has emerged as one of the most up-and-coming non-invasive therapeutic modalities for cancer therapy in rencent years. However, its therapeutic effect was still hampered by the short life span, limited diffusion distance and ineluctable depletion of singlet oxygen (1O2), as well as the hypoxic microenvironment in the tumor tissue. Such problems have limited the application of PDT and appropriate solutions are highly demand. Methods: Herein, a programmatic treatment strategy is proposed for the development of a smart molecular prodrug (D-bpy), which comprise a two-photon photosensitizer and a hypoxia-activated chemotherapeutic prodrug. A rhodamine dye was designed to connect them and track the drug release by the fluorescent signal generated through azo bond cleavage. Results: The prodrug (D-bpy) can stay on the cell membrane and enrich at the tumor site. Upon light irradiation, the therapeutic effect was enhanced by a stepwise treatment: (i) direct generation of 1O2 on the cell membrane induced membrane destruction and promoted the D-bpy uptake; (ii) deep tumor hypoxia caused by two-photon PDT process further triggered the activation of the chemotherapy prodrug. Both in vitro and in vivo experiments, D-bpy have exhabited excellent tumor treatment effect. Conclusion: The innovative programmatic treatment strategy provides new strategy for the design of follow-up anticancer drugs.
- Subjects :
- Combination therapy
medicine.medical_treatment
Cell
Medicine (miscellaneous)
Photodynamic therapy
02 engineering and technology
010402 general chemistry
01 natural sciences
two-photon photodynamic therapy
combination therapy
In vivo
medicine
Animals
Humans
Prodrugs
Photosensitizer
glutathione
Hypoxia
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Fluorescent Dyes
Photons
Chemotherapy
Photosensitizing Agents
Singlet Oxygen
Staining and Labeling
Tumor hypoxia
Rhodamines
Chemistry
Cell Membrane
Mammary Neoplasms, Experimental
Prodrug
021001 nanoscience & nanotechnology
humanities
0104 chemical sciences
medicine.anatomical_structure
Photochemotherapy
Cancer research
Female
0210 nano-technology
Azo Compounds
Research Paper
HeLa Cells
Subjects
Details
- ISSN :
- 18387640
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....80848620689f43f0275e952494decdfb