Self-Assembled Chlorin e6 Conjugated Chondroitin Sulfate Nanodrug for Photodynamic Therapy

Abstract

Acetylated-chondroitin sulfate/chlorin e6 conjugates (Ac-CS/Ce6 1, 2, 3) were synthesized via the formation of an ester linkage between CS and Ce6 and evaluated as nanoscale drugs for photodynamic therapy. Ac-CS/Ce6 2 and 3 with higher Ce6 contents of 11.7 and 17.6%, respectively, had average diameters of <150 nm and were very stable in phosphate-buffered saline (PBS) for 1 month. The critical self-quenching concentration (CQC) of Ac-CS/Ce6 decreased as the conjugated-amount of Ce6 increased. All samples displayed autophotoquenching properties in aqueous solution, whereas their fluorescence intensity strongly correlated with the amount of Ce6 in the organic solvent dimethyl sulfoxide (DMSO). Compared with free Ce6, Ac-CS/Ce6 nanodrug photoactivity was maintained in terms of fluorescence properties and singlet oxygen ((1)O(2)) generation. In a HeLa cell culture system, we observed rapid cellular uptake of the Ac-CS/Ce6 nanodrug without any other ligands using confocal imaging and fluorescence-activated cell sorting (FACS) analysis. Upon light irradiation following cellular uptake, phototoxicity was detected via 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The self-quenching effect and fluorescence recovery of Ac-CS/Ce6 were also determined both in vitro and in vivo. Taken together, our results indicate that Ac-CS/Ce6 has potential as an effective photodynamic therapy (PDT) prodrug for clinical application.

Chondroitin sulfate functionalized mesostructured silica nanoparticles as biocompatible carriers for drug delivery

“…This character suggests that ChS is potentially a good candidate for usage as a drug carrier. [27][28][29][30] Recently, we used a method of interfacial polymerization in emulsion to fabricate chondroitin sulfatebased nanocapsules for loading of indomethacin. 31 The shell of nanocapsules consisted of the cross-linked ChS chains, and showed a much higher drug loading capacity.…”

Polymeric Photosensitizer Nano-drugs for Long Term Therapeutic Effect: in vitro and in vivo Phototoxicity against Human Colon Cancer (HCT-116)

“…Our group has previously described the high AA modification for HyalA and ChonS to increase hydrophobicity, forming self-assembled Nano-drugs [14,15]. In this work, with a small feed of AA for the offer of hydrophobicity to provide only DMSO-soluble polymers, the low acetylation guaranteed that more functional groups on the HyalA and ChonS were available to the further conjugation according to the synthetic scheme illustrated in Scheme 1.…”

A charge-reversible nanocarrier using PEG-PLL(-<em>g</em>-Ce6, DMA)-PLA for photodynamic therapy

“…However, the CDTM showed a high absorbance spectrum due to the improved water solubility of Ce6 after conjugation with the lysine residue. 14,37 In vitro evaluation of cDTM It is well known that nanoparticles employ multiple endocytic pathways to enter cells; especially, positively charged nanoparticles are well suited for endocytic cellular uptake because they can interact favorably with negatively charged cell membrane components. 16,17 Thus, we used flow cytometry to examine the effects of CDTM surface charge reversibility on the cellular uptake of a drug in KB cells.…”