Crosslinked polymeric self-assemblies as an efficient strategy for photodynamic therapy on a 3D cell culture

Abstract

Polymeric crosslinked self-assemblies based on poly(ethyleneoxide-b-ε-caprolactone) have been synthesized. They are shown to be more efficient vectors for photodynamic therapy compared to uncrosslinked systems.

Photodynamic therapy in 3D cancer models and the utilisation of nanodelivery systems

“…plates, hanging drop methods etc.) where they assume naturally a spherical aggregate conformation [67][68][69] or by embedding cells in a 3D matrix. The closely packed arrangement where cell to cell contact is dominant and the reduced rate of diffusion of drugs and oxygen through the spheroids makes them comparable to in vivo tissues.…”

“…129 Yang et al (2015) 121 also observed a more homogenous response where the dead cells were found to be distributed across the full thickness of the cancer tissue in the 3D model post-treatment with 5-ALA and AuNPs combined, whereas with 5-ALA-only PDT, a majority of the dead cells were identified within the superficial parts of the cancer tissue. Till et al (2016) 68 on the other hand used 3D spheroid models developed from human colorectal carcinoma cell line (HCT-116) and human squamous cell carcinoma cell line (FaDu) on ultra-low attachment plates for investigating PDT efficacy. This study compared PDT using a pheophorbide photosensitiser (Pheo) in free solution form to the use of encapsulated photosensitiser in crosslinked polymeric micellar self-assemblies versus uncrosslinked micellar counterparts.…”

Rational design of block copolymer self-assemblies in photodynamic therapy

“…The most frequently suggested solution to avoid any dissociation upon dilution is cross-linking of the vector. For PDT and other therapeutic cases this has been also described [66], showing a strong improvement of the treatment. The PS can be used both as ROS generator and also as cross-linker [101].…”

“…PIC with PS HUVEC and lung carcinoma, in vitro [46,47] poly(ethylene oxide)-block-poly(α,β-aspartic acid)/poly([5-aminopentyl]-α,β-aspartamide) -lung carcinoma, in vitro [48] poly(ethylene oxide)-block-poly(α,β-aspartic acid) PIC with PS lung carcinoma, in vitro [49] poly(N-methyl-2-vinylpyridinium iodide)-block-poly(ethylene oxide) PIC with PS - [50,51] [64] poly(oligo(ethylene oxide)methyl ether methacrylate)-block-poly(ʟ-lysine) O 2 production image-guided (FI), liver and breast cancer, in vitro [65] methoxy-poly(ethylene oxide)-block-poly(ε-caprolactone)-benzyl degradation macrophages and endothelial cells, in vitro [40] poly(ethylene oxide)-block-poly(ε-caprolactone) degradation colon cancer and carcinoma, in vitro [37,66,67] poly(ethylene glycol)-block-poly(lactic acid) degradation [38] poly(ethylene glycol)-block-poly(ᴅ,ʟ-lactide-co-benzyl glycidyl ether) degradation macrophage and kidney cells, in vitro [45] poly(ethylene glycol)-block-poly(ε-caprolactone)-block- aliphatic polyesters, based for instance on ε-caprolactone or lactic acid [36][37][38][39][40][41]. In particular, the degradation of polyesters in vivo, a combination of both hydrolytic and enzymatic processes, makes them a first choice for the controlled delivery of drugs [42].…”

“…Recent reviews have shown the importance of controlling the shape of the vectors, both for cell penetration but also for the behavior in the blood stream [142]. Regarding PDT more specifically, Till et al examined the PDT efficiency of pheophorbide a when incorporated in micellar, vesicular or worm-like PEO-PCL vectors in two cell lines (FaDu or HCT 116) [66,67]. No strong improvement was observed for elongated systems working on 3D spheroids and, interestingly, a micelle/vesicle mixture led to synergistic effects on HCT 116 cells but antagonistic effects for FaDu cells [67].…”