Pu-18-N-butylimide-NMGA-GNP conjugate is effective against hepatocellular carcinoma

Abstract

BackgroundPhotodynamic therapy (PDT) is a new modality in the treatment of cancer. This study thus aims to examine whether the PDT is effective against in vivo hepatocellular carcinoma.MethodsIn vivo efficacy of PDT on hepatocellular carcinoma was tested in xenografted mice with human hepatocellular carcinoma cell lines (Huh7) by utilizing a gold nanoparticles (GNPs) conjugate of new photosensitizer (PS), purpurin-18-N-butylimide-N-methyl-D-glucamine (Pu-18-N-butylimide-NMGA). The conjugate (PS-GNPs) was synthesized from the reaction between Pu-18-N-butylimide-NMGA and chloroauric acid (HAuCl4). Mice were arbitrarily assigned into one of three groups. First group received saline alone, second group received PS-GNPs alone, and the last group received both PS-GNPs and irradiation. PS-GNPs was injected directly into the tumor mass and irradiations were performed 24 hours after injection of PS-GNPs.ResultsTumor volume was significantly smaller in the group which received both PS-GNPs and irradiation compared with other two groups. Western blot and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay revealed that the group which received both PS-GNPs and irradiation showed larger amount of apoptotic protein and DNA fragmentation compared with other two groups.ConclusionThis study suggests that Pu-18-N-butylimide-NMGA-GNP conjugate is an effective agent for PDT in the treatment of hepatocellular carcinoma.

PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer

“…For column chromatography, silica gel (30-60 µm, SiliTech, MP Biomedicals, Eschwege, Germany) was used. 6,9 .1 11,14 .1 16,19 .0 2,7 ]heptacosa-1(24),2(7),6(27),9,11 (26) 36 To a solution of compound 1 (30 mg, 53 µmol) in chloroform (7 mL), Zn(OAc) 2 •2H 2 O (117 mg, 0.53 mmol; in 3 mL of MeOH) was added. This mixture was stirred for 12 h at 45 • C. The solvents were removed under reduced pressure and the residue was chromatographed (CHCl 3 -MeOH, 40/1).…”

“…The photoactivation of a PS results in an acute stress response that leads to changes in calcium ion concentration and lipid metabolism, as well as the production of cytokines and stress response mediators [60]. These responses hamper mitochondrial processes, resulting in reactive oxygen species production and, consequently, in damage to the mitochondrial membrane; such damage induces cytochrome c release into cytosol [7], which, in turn, causes apoptosis. In addition to apoptosis, at excessive PS concentrations, PDT can also lead to cell death via necrosis; sometimes, a combination of both apoptosis and necrosis is involved.…”

“…RF = 0.2 in DCM-MeOH, 10/1. 1 H NMR (400 MHz, CD3OD) δ: 1.30 (t, J 6,9 .1 11,14 .1 16,19 .0 2,7 ]heptacosa-1 24 and HOBt (37 mg, 0.27 mmol) were added. The mixture was stirred for 5 min, after which DIC (50 mg, 0.4 mmol in 1 mL of THF) was added and the mixture was stirred for 24 h. Then, the solvent was evaporated and the residue was filtered through a short pad of silica (DCM-MeOH, 25/1) to obtain the crude product (250 mg), RF = 0.5 (DCM-MeOH, 20/1).…”

“…RF = 0.48 in DCM-MeOH, 10/1. 1 6,9 .1 11,14 .1 16,19 .0 2,7 ]heptacosa-1(24),2(7),6(27),9,11 (26), 12,14,16,18,20-…”

“…Various modified substructures derived from their basic core have been discovered within the plant kingdom [1][2][3][4]. Owing to their strong absorption between 650-700 nm, wavelengths that penetrate tissue effectively, chlorins have been investigated as photosensitizers (PSs) for use in the photodynamic therapy (PDT) of cancerous and noncancerous diseases [5][6][7][8].…”