Low-density lipoprotein encapsulated thiosemicarbazone metal complexes is active targeting vehicle for breast, lung, and prostate cancers

Abstract

Cancer is a leading cause of death worldwide and affects society in terms of the number of lives lost. Current cancer treatments are based on conventional chemotherapy which is nonspecific in targeting cancer. Therefore, intensive efforts are underway to better target cancer-specific cells while minimizing the side effects on healthy tissues by using LDL particles as active drug delivery vehicles. The goal is to encapsulate anticancer agents thiosemicarbazone metal-ligand complexes into LDL particles to increase the cytotoxic effect of the agent by internalization through LDL receptors into MCF7, A549, and C42 cancer cell lines as segregate models for biological evaluations targeting tubulin. Zeta potential data of LDL-particles encapsulated anticancer agents showed an acceptable diameter range between 66–91 nm and uniform particle morphology. The results showed cell proliferation reduction in all tested cell lines. The IC 50 values of LDL encapsulated thiosemicarbazone metal-ligand complexes treated with MCF7, A549, and C42 ranged between 1.18–6.61 µM, 1.17–9.66 µM, and 1.01–6.62 µM, respectively. Western blot analysis showed a potent decrease in tubulin expression when the cell lines were treated with LDL particles encapsulated with thiosemicarbazone metal-ligand complexes as anticancer agents. In conclusion, the data provide strong evidence that LDL particles are used as an active drug delivery strategy for cancer therapy.

Cancer targeted drug delivery using active low-density lipoprotein nanoparticles encapsulated pyrimidines heterocyclic anticancer agents as microtubule inhibitors

“…The results possessed cancer cell growth inhibition in both tested cell lines even at one µM concentration. In our previous project, we proved that plain LDL particles treated with cancer cells do not affect cell growth (Jaragh-Alhadad et al, 2022b ). DU145 and MDA468 Cells treated with ten µM, concentration showed IC 50 values ranging between 1.11–5.94 µM, and 1.21–5.05 µM, respectively.…”

“…Any drug delivery strategy starts with the agents’ stability both at 37 °C for treatment and at 4 °C for storage which proven previously (Abdellatif et al, 2021 ; Jaragh-Alhadad et al, 2022b ). Several studies proved that LDL particles were stable until three months (Alhadad et al, 2020 ; Jaragh Alhadad, 2021 ; Jaragh-Alhadad et al, 2022b ) and Abdellatif et al confirmed that silver nan-particles physical stability reached up to three months at the following temperatures 25 ± 0.5 °C and 4.0 ± 0.5 °C (Abdellatif et al, 2021 ). Another study, in 2021 encapsulated anticancer agents into nano carbon core and the results prove the nanoparticles stability within two months and enabling the efficient tumor accumolation (Zhang et al, 2021 ).…”

“…Agent 30a particle size was 377 nm and reached 723 nm because of the nano-rods morphology. Generally, LDL particles became bigger after encapsulation with the anticancer agents based on the size of the plain LDL ( Figure 4B ) (Abdellatif et al, 2016 ; Abdellatif, 2020 ; Abdellatif et al, 2021 ; Jaragh-Alhadad et al, 2022b ).…”

“…This will form anticancer agents coated with LDL particles and each sample will have a specific LDL particle size based on its nano size and morphology either rod, fibers, clusters, or nanoparticles structures. Increasing the LDL particles size after encapsulation indicates the successful loading and encapsulation of the anticancer agents into the nano LDL particles core (Alhadad et al, 2020 ; Jaragh Alhadad, 2021 ; Jaragh-Alhadad et al, 2022b ).…”

“…Also, an increase of the drug concentration to 10 µM will cause more cell death than 1 µM and this suggest the strength of the interactions of the anticancer agents with the cellular tubulin protein after internalization process. Further, incubation time of LDL particles encapsulated anticancer agents with the tested cell lines at 48 h showed potent activities more than 24 h treatments (Wang et al, 2019 ; Jaragh-Alhadad et al, 2022b ).…”