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Abstract To overcome the drug resistance in MCF7 cancer cells and enhance their sensitivity to cisplatin, a liposomal (Lip) nanocarrier modified by arginine-glycine-aspartic acid (RGD) to co-deliver cisplatin (Cis) and miRNA biomolecule (miR-34a) was investigated. The efficiency of this nanocarrier was evaluated through in vitro and in vivo assays against MCF7 and 4T1 cells, respectively. The in vitro results demonstrated that the miR34a-Cis-Lip-RGD formulation had significantly higher efficiency and also a higher apoptotic effect compared to both miR34a-Cis and miR34a-Cis-Lip (76.24%, 58.29%, and 56.2%, respectively). Additionally, miR34a-Cis-Lip exhibited an overall CI value below 1, indicating a synergistic effect of Cis and miR-34a within the Lip system. The miR34a-Cis-Lip-RGD increased the Bax gene expressions compared to both miR34a-Cis-Lip and Cis-miR34a, possibly due to the integrin receptors on the cells, leading to higher uptake. The efficiency of miR34a-Cis-Lip-RGD in reducing tumor size was significantly higher than Cis-miR34a and miR34a-Cis-Lip. The lower volume of the tumor in the group treated with Cis-miR34a-Lip-RGD is presumed to be attributed to improved cellular uptake facilitated by the RGD modification, which enhances the targeted delivery of the therapeutic payload to cancer cells. The overall weight of the mice in all the groups did not exhibit significant changes. This consistent weight maintenance implies the safety of the designed delivery system for vital organs, indicating that the designed delivery system may offer a promising solution to minimize unwanted side effects associated with conventional cancer treatments.

Background: Quercetin is a flavonoid having anti-cancer properties; however, it has low stability, insufficient bioavailability, and poor solubility. This study aimed to load quercetin on nanoliposomes to enhance its efficiency against SW48 colorectal cancer cells. The cytotoxicity of free-quercetin and quercetin-loaded nanoliposomes on the expression of the epidermal growth factor receptor (EGER) gene was investigated. Methods: This present in vitro study was conducted at Yasuj University of Medical Sciences (Yasuj, Iran) in 2021. In this in vitro study, the lipid thin-film hydration method was used to synthesize quercetin-loaded liposomes. Additionally, high-performance liquid chromatography (HPLC) analyses, dynamic light scattering (DLS), and transmission electron microscopy (TEM) investigations were used to characterize nanomaterials. Following that, MTT, flow cytometry, and real-time PCR were used to investigate the cytotoxicity of quercetin-loaded liposomes on the colorectal cancer cells SW48 cell line, the incidence of apoptosis, and the expression of the EGFR gene in these cells. Statistical analysis was performed using the SPSS (version 26.0), and the graphs were created with the GraphPad Prism version 8.4.3. P

Curcumin is one of the natural anticancer drugs but its efficiency is limited by low stability, insufficient bioavailability, poor solubility, and poor permeability. Dorema aucheri (Bilhar) is a herb with precious pharmaceutical properties. This study aimed to develop a nanoliposome-based curcumin and Bilhar extract codelivery system. The nanocompounds were synthesized using the lipid thin-film hydration method and characterized by transmission electron microscopy, and dynamic light scattering techniques, and their cytotoxicity and apoptotic effect on the primary oral cancer cell line were evaluated via 2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry. Moreover, the expression of the epidermal growth factor receptor (EGFR) gene in the treated cells was assessed using the real-time polymerase chain reaction technique. Based on the results, nanoliposomes had a size of 91 ± 10 nm with a polydispersity index of 0.13. Free curcumin, the extract, and the curcumin-extract combination showed dose-dependent toxicity against cancer cells; yet, the extract (IC50: 86 µg/ml) and curcumin-extract (IC50: 65 µg/ml) activities were much more than curcumin (IC50: 121 µg/ml). Also, the curcumin and extract loaded on liposomes showed a dose and time-dependent cytotoxicity. After loading the curcumin-extract compound on nanoliposomes, their IC50 decreased from 180 µg/ml (within 24 hr) to 43 µg/ml (within 72 hr), indicating their sustainable release and activity. Likewise, this compound induced the highest apoptosis percentage (95%) in cancerous cells and inhibited the expression of the EGFR gene in the cells by 81% ± 3%. These findings demonstrated the effectiveness of the Bilhar extract against oral cancer cells. Also, in combination with curcumin, it showed an additive activity that considerably improved after loading on nanoliposomes.

To overcome the drug resistance in MCF7 cancer cells and enhance their sensitivity to cisplatin, a liposomal (Lip) nanocarrier modified by arginine-glycine-aspartic acid (RGD) to co-deliver cisplatin (Cis) and miRNA biomolecule (miR-34a) was investigated. The efficiency of this nanocarrier was evaluated through in vitro and in vivo assays against MCF7 and 4T1 cells, respectively. The in vitro results demonstrated that the miR34a-Cis-Lip-RGD formulation had significantly higher efficiency and also a higher apoptotic effect compared to both miR34a-Cis and miR34a-Cis-Lip (76.24%, 58.29%, and 56.2%, respectively). Additionally, miR34a-Cis-Lip exhibited an overall CI value below 1, indicating a synergistic effect of Cis and miR-34a within the Lip system. The miR34a-Cis-Lip-RGD increased the Bax gene expressions compared to both miR34a-Cis-Lip and Cis-miR34a, possibly due to the integrin receptors on the cells, leading to higher uptake. The efficiency of miR34a-Cis-Lip-RGD in reducing tumor size was significantly higher than Cis-miR34a and miR34a-Cis-Lip. The lower volume of the tumor in the group treated with Cis-miR34a-Lip-RGD is presumed to be attributed to improved cellular uptake facilitated by the RGD modification, which enhances the targeted delivery of the therapeutic payload to cancer cells. The overall weight of the mice in all the groups did not exhibit significant changes. This consistent weight maintenance implies the safety of the designed delivery system for vital organs, indicating that the designed delivery system may offer a promising solution to minimize unwanted side effects associated with conventional cancer treatments. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common and deadly cancers worldwide. Different factors, such as environmental and genetic factors and lifestyle, affect it. Owing to the presence of phenolic, alkaloid, antioxidant, and terpenoid compounds, herbal compounds can be effective in the treatment of various cancers. Thymol is a natural monoterpene phenol that is abundant in some plants and exerts several biological effects. The aim of this study was to investigate the apoptotic, anti-proliferative effect and EGFR gene expression under the influence of thymol-loaded nanoliposome in SW84 and SW111 cell lines derived from colorectal cancer. Materials and methods: The lipid thin-film hydration method was used to synthesize thymol-loaded liposomes, and their characterization was performed using TEM, DLS, and HPLC analyses. SW84 and SW1111 cells were treated with thymol- and thymol-loaded liposomes at different doses, the inhibition of cell proliferation was evaluated using an MTT assay, the rate of apoptosis induction was assessed using flow cytometry, and EGFR gene expression was measured using real-time PCR. Results: The nanoparticles produced were spherical, uniform, and 200 ± 10 nm in size. HPLC analysis showed that approximately 98% thymol was loaded into the nanoliposome. The results of the MTT assay showed that thymol and thymol-nanoliposomes decreased the proliferation of SW84 and SW1111 cells in a concentration-dependent manner. The IC50 of thymol and thymol-nanoliposomes were 18 and 14.2 µg/ml for the SW48 cell line (P = 0.04) and 10.5 and 6.4 µg/ml for the SW1116 cell line (P = 0.001). Thymol-nanoliposomes significantly inhibited the proliferation of cancer cells compared to free thymol. Flow cytometry showed an increase in the percentage of apoptotic cells, especially in the thymol-nanoliposome group in the treated cells. Real-time PCR results also showed that thymol and thymol-nanoliposome both caused a decrease in the expression of EGFR genes in both cell lines, but this effect of decreasing gene expression was significantly higher in the thymol-nanoliposome group. Conclusions: Our results showed that thymol-nanoliposomes reduced proliferation, increased apoptosis, and decreased EGFR expression in colorectal cancer-derived cell lines. [ABSTRACT FROM AUTHOR]

Nanotechnology and drug co-delivery offer a novel avenue in drug delivery research liposome-based co-delivery of anticancer drugs targeting the apoptosis pathway as a promising new approach to treat cancer. In this study, a co-delivery system of liposomes (arsenic trioxide/curcumin) modified with RGD peptide was designed to aim for enhancing the treatment of prostate cancer cells (PC3 cell line). Liposomal co-loaded curcumin and arsenic trioxide modified by RGD peptide (NLPs-RGD-Cur-ATO) were prepared by thin-layer lipid hydration techniques for the treatment of prostate cancer. The stability of the NLPs-RGD-Cur-ATO was evaluated by particle size analysis through dynamic light scattering (DLS) analysis and transmission electron microscopy (TEM). The percentage of cytotoxicity and apoptotic effect in PC3 cells treated with NLPs-RGD-Cur-ATO were detected by MTT and Annexin V-FITC (fluorescein isothiocyanate)/PI affinity assay, respectively. The particle size of NLPs-RGD-Cur-ATO was approximately 100 nm, with an encapsulation efficiency of about 99.52% and 70.61%, for ATO and Cur, respectively. Besides, NLPs-RGD-Cur-ATO displayed an enhanced anti-proliferative effect, increased the percentage of apoptotic cells 98 ± 1.85% (p < 0.0001), and significantly reduced EGFR gene expression level (p < 0.001) in the cell line tested. These results indicated that our NLPs-RGD-Cur-ATO co-delivery system was a promising strategy for prostate cancer therapy. [ABSTRACT FROM AUTHOR]

During the past few years, advances in drag delivery have provided many opportunities in the treatment of various diseases and cancer. Arsenic trioxide (ATO) and Erlotinib (Erlo) are two drugs, approved by the United States Food and Drug Administration to treat cancer, but their use is limited in terms of the toxicity of ATO and the low solubility of Erlo. This study aimed to prepare arginine‐glycine‐aspartic acid (RGD)‐decorated nanoliposomes (NLPs) containing Erlo and ATO (NLPs–ATO–Erlo–RGD) to increase the solubility and reduce the toxicity of Erlo and ATO for cancer treatment. The results of transmission electron microscopy and dynamic light scattering showed that NLPs were synthesized uniformly, with spherical shape morphology and particle sizes between 140 and 160 nm. High‐performance liquid chromatography and ICP–MS results showed that about 90% of the drug was loaded in the NLPs. In comparison with NLPs–ATO–Erlo, NLPs–ATO–Erlo–RGD demonstrated considerable toxicity against the αvβ3 overexpressing PC3 cell line in the MTT experiment. It had no effect on the PANC‐1 cell line. In addition, apoptosis assays using Annexin V/PI demonstrated that NLPs–ATO–Erlo–RGD generated the highest apoptotic rates in PC3 cells when compared with NLPs–ATO–Erlo and the combination of free ATO and Erlo. Furthermore, treatment with NLPs–ATO–Erlo–RGD in (p < 0.05) PC3 cell line significantly reduced EGFR level. It is concluded NLPs–ATO–Erlo–RGD as a novel drug delivery system may be a promising platform for the treatment of cancer. [ABSTRACT FROM AUTHOR]