Photosensitizer localization in amphiphilic block copolymers controls photodynamic therapy efficacy

Abstract

Localization of the photosensitizer conjugation site in amphiphilic block copolymers is shown to have a great impact on photodynamic therapy efficiency. To this end, an asymmetric multifunctional derivative of the azadipyrromethene boron difluoride chelate (aza-BODIPY) was synthesized and inserted at specific locations in polypeptide-based rod-coil amphiphilic block copolymers. A study of the photophysical properties of the vesicle nanocarriers, obtained by self-assembly of these copolymers, as well as in vitro tests on two cancer cell lines were performed. This study aims at providing guidelines for the optimization of the synthetic design of therapeutic nanomedicines with minimal amounts of photosensitive molecules.

Visible‐Light Photoactive, Highly Efficient Triplet Sensitizers Based on Iodinated Aza‐BODIPYs: Synthesis, Photophysics and Redox Properties

“…Owing to their advantageous and tunable photophysical properties and ability to generate singlet oxygen ( 1 O 2 )c oupled with absorption of light from the socalled "therapeuticw indow"( 600 nm-1100 nm), aza-BODIPY dyes have been proposed as potential triplet photosensitizers for both anti-microbiala nd anti-cancer photodynamic therapy. [20,[30][31][32][33][34][35][36][37][38][39][40][41] Aza-BODIPYs continue to attracta ttention as chemosensors for the detection of ammonia, [42] cysteine, homocysteine and glutathione in living cells, [43] Hg 2 + , [44][45][46] F À , [47,48] in vivo detection of H 2 S, [49] carbon dioxide, [50] glucosei nw hole blood, [51] detection of saxitoxin [52] and pH-sensitive sensors. [52] Furthermore, aza-BODIPYs have been proposed as photoactive components in photovoltaic devices [54][55][56] and nonlinear optical materials.…”

Optimized reconstitution of membrane proteins into synthetic membranes

“…As FCS only detects objects associated with PR-GFP, we could potentially detect different vesicle populations. Evidence for a good correlation of sizes obtained by DLS/FCS and micrographs haven been presented for liposomes 36,37 and PDMS-PMOXA polymersomes [38][39][40][41] , even though direct methods like (cryo-)TEM are considered more precise. The polydispersity index (PdI), obtained from cumulants analysis, was utilized as a measure for homogeneity.…”

Near‐Infrared Photoactive Aza‐BODIPY: Thermally Robust and Photostable Photosensitizer and Efficient Electron Donor

“…Replacement of the meso‐carbon atom with an aza‐bridge results in a bathochromic shift of both absorption ( λ abs ) and emission ( λ fl ) bands of around 80 nm. Owing to their advantageous photophysical properties (triplet lifetimes τ T , triplet state quantum yields Φ T and triplet state energies E T ) combined with tunable singlet oxygen quantum yields (Φ Δ ) and ability to absorb light from the “therapeutic window”, aza‐BODIPYs have been proposed as potential triplet photosensitizers for both anti ‐microbial and anti ‐cancer photodynamic therapy . Furthermore, aza‐BODIPYs were considered as fluorescent chemosensors for the detection of ammonia, cysteine, homocysteine and glutathione in living cells, Hg 2+ , F − , in vivo detection of H 2 S and NO, carbon dioxide, glucose in whole blood and pH‐sensitive sensors .…”