Efficacy of Gold and Nickel on the Anticancer Activity and Physical Properties of Pemetrexed Loaded on Fullerene C60 Buckysomes

Abstract

Objective: This study aims to create a new delivery system for pemetrexed, employing a metal-C60 fullerene combination for the first time. Additionally, a lung cancer cell line study will be used to examine the impact of this combination on the release, behavior, and drug’s cytotoxicity. Methods: To utilize a laser to irradiate hydrocarbons, fullerene C60 (Buckysomes) was produced and then nanosized by adding different volumes of isopropyl alcohol and ultrasonication. Gold Nanoparticles (AuNPs) and nickel nanoparticles (NiNPs) were also prepared each one separately and added to the previous mixture together with Pemetrexed (PMX) with further ultrasonication for 20 minutes. The mixture is kept in the refrigerator for 20 hours and then filtered. The precipitate was dried and characterized for particle size, invitro release, and anticancer activity in comparison to pemetrexed loaded on C60 fullerene previously prepared in our laboratory. Results: The evaluation techniques revealed the successful loading of pemetrexed on metals- fullerene C60 nanocarrier, SG10 was the optimum sample with % of yield reach to 95.36. The release profile shows that the percentage release of pemetrexed after 240 minutes is equal to 40% from pure PMX, while the release after 240 minute was found to be 87.8 % from pemetrexed loaded gold nanoparticles (AuNPs) fullerene C60 nanocarrier (SG10), while NiNPs not significantly improved the release profile of Pemetrexed from Pemetrexed loaded NiNPs – fullerene (SN7). Pemetrexed loaded on gold nanoparticles (AuNPs), when compared to pure PMX (3.1 M) and SN7 (11.5 M), fullerene nanocarrier (SG10) exhibits a lower IC50 (1.55 M) and a greater cytotoxic effect (high IR percent) on A549 cancer cells. Pemetrexed’s cytotoxicity in A549 was enhanced after being loaded onto gold nanoparticles (AuNPs)-fullerene nanocarriers (90.4% cell death for SG10) as opposed to pure drug (60% cell death). This finding suggests that the loading process enhanced the drug’s cytotoxic activity for the tumor cells, which may have sped up the onset of action (30% cell death after 24 hours). Conclusion: This study successfully prepared Metals- fullerene C60 Buckysomes loaded with pemetrexed utilizing gold and nickel, which may serve (especially Au- fullerene) as a suitable nanocarrier for pemetrexed, resulting in an improvement to solubility, the release pattern, and cytotoxicity.

Prospective effect of linkers type on the anticancer activity of pemetrexed-monoclonal antibody (atezolizumab) conjugates

“…66 The time response curve (Figure 14) shows that with 12.5 μM of pure PMX at 24 h gave (39.58% cell death), at 48 h (48.39% cell death) and 72 h (78.70% cell death) indicating the drug activity is time dependent, which agreed with reported data for PMX. 29,67 AtZ mAb with 12.5 μM concentration at 24 h lead to (52% cell death), at 48 h (63% cell death) and 72 h (85.14% cell death). which was also time dependent and agreed with reported data for AtZ, 68 but it was significantly (P≤ 0.05) higher than PMX confirming the potency (as well as selectivity) of the mAb as anticancer agent.…”

Prospective effect of linkers type on the anticancer activity of pemetrexed-monoclonal antibody (atezolizumab) conjugates

“…66 The time response curve (Figure 14) shows that with 12.5 μM of pure PMX at 24 h gave (39.58% cell death), at 48 h (48.39% cell death) and 72 h (78.70% cell death) indicating the drug activity is time dependent, which agreed with reported data for PMX. 29,67 AtZ mAb with 12.5 μM concentration at 24 h lead to (52% cell death), at 48 h (63% cell death) and 72 h (85.14% cell death). which was also time dependent and agreed with reported data for AtZ, 68 but it was significantly (P≤ 0.05) higher than PMX confirming the potency (as well as selectivity) of the mAb as anticancer agent.…”

“…The A549 cell suspensions were dispensed into 96-well flat plates in a concentration of 5 x 10 3 cells per well, incubated for 1 day under standard conditions; 4 x 10 3 cells per well, incubated for 2 days; and 3 x 10 3 cells per well, incubated for 3 days under standard conditions. 29,30 Cells were treated with same concentration range 0.05-100 μM of each sample, control group with only growth medium included within plate and plate incubated. After a 24 h, 48 h, and 72 h incubation, the cell culture medium was removed (after each recovery period) and incubated with MTT solution (3-(4,5-Dimethyl thiazol-2-yl)-2,5 Diphenyl tetrazolium Bromide), the medium was removed and DMSO was added to plates (remained at room temperature in the dark for fifteen minutes).…”

“…The FTIR spectrum (Figure 2) of pure PMX displaced the characteristic stretching band O-H of COOH near 3400 cm -1 , stretching NH 2 at 3309.85 cm -1 , stretching NH at 2970.38 cm -1 , stretching C-H aliphatic at 2877.79 cm -1 , C=O of COOH at 1689 cm -1 , C=C aromatic at 1527.62 cm -1 , and all these peaks similar to that reported. 29 The α-amine-ω-propionic acid tetra ethylene glycol (NH 2 -PEG 4 -COOH) displaced characteristics stretching C=O of COOH at 1631.78 cm -1 , stretching band O-H of COOH at 3514.30 cm -1 . 34 The mixture of PMX and PEG showed the same characteristics peaks observed in each ingredient separately with observable broadening in C=O of COOH at 1631.78 and 1697.36 cm -1 , which are for C=O of COOH of the PEG and PMX, respectively.…”

Pemetrexed loaded gold nanoparticles as cytotoxic and apoptosis inducers in lung cancer cells through ROS generation and mitochondrial dysfunction pathway

“…37 A similar observation was made in the case of pemetrexed loaded onto AuNPs with Fullerene (SG10). 38 UV-Vis spectrophotometry of AuNPs with a citrate coating had an absorption peak at 520 nm, and PEM-AuNPs demonstrated a peak at 530 nm, which was shifted by 10 nm due to the loading of PEM on AuNPs (Figure 3). This variation is because PEM loading on the surface of AuNPs causes a change in the dielectric constant of AuNPs.…”