Edward R. H. Walter, Peter Kam-Keung Leung, Lawrence Cho-Cheung Lee, Kenneth Kam-Wing Lo, Nicholas J. Long
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引用次数: 0
Abstract
The development of new and improved mitochondria-targeting photosensitisers (PSs) for photodynamic therapy (PDT) remains highly desirable, due to the critical role the mitochondria play in maintaining healthy cellular function. Here, we report the design, synthesis, photophysical properties and biological characterisation of a series of di-iodinated BODIPY-based PSs, BODIPY-Mito-I-n, for mitochondria-targeted PDT applications. Six BODIPY-Mito-I-n analogues were synthesised in good yields, with fast reaction times of between 30 and 60 min under mild conditions. The di-iodination of the BODIPY scaffold enabled highly efficient population of the triplet state, leading to high singlet oxygen (1O2) photosensitisation efficiencies (ΦΔ = 0.55–0.65). All BODIPY-Mito-I-n compounds exhibited very high photocytotoxic activity towards HeLa cells, with IC50,light values of between 1.30 and 6.93 nM, due to photoinduced 1O2 generation. Notably, the poly(ethylene glycol) (PEG)-modified BODIPY-Mito-I-6 showed remarkably lower dark cytotoxicity (IC50,dark = 6.68–7.25 μM) than the non-PEGylated analogues BODIPY-Mito-I-1 to BODIPY-Mito-I-5 (IC50,dark = 0.58–1.09 μM), resulting in photocytotoxicity indices up to 2120. Mechanistic studies revealed that BODIPY-Mito-I-6 induced reactive oxygen species overproduction and mitochondrial dysfunction in cells upon irradiation, leading to significant cell death through a combination of apoptosis and necrosis. It is anticipated that our design will contribute to the development of more effective mitochondria-targeting PSs for cancer therapy.
期刊介绍:
Journal of Materials Chemistry A, B & C cover high quality studies across all fields of materials chemistry. The journals focus on those theoretical or experimental studies that report new understanding, applications, properties and synthesis of materials. Journal of Materials Chemistry A, B & C are separated by the intended application of the material studied. Broadly, applications in energy and sustainability are of interest to Journal of Materials Chemistry A, applications in biology and medicine are of interest to Journal of Materials Chemistry B, and applications in optical, magnetic and electronic devices are of interest to Journal of Materials Chemistry C.Journal of Materials Chemistry B is a Transformative Journal and Plan S compliant. Example topic areas within the scope of Journal of Materials Chemistry B are listed below. This list is neither exhaustive nor exclusive:
Antifouling coatings
Biocompatible materials
Bioelectronics
Bioimaging
Biomimetics
Biomineralisation
Bionics
Biosensors
Diagnostics
Drug delivery
Gene delivery
Immunobiology
Nanomedicine
Regenerative medicine & Tissue engineering
Scaffolds
Soft robotics
Stem cells
Therapeutic devices