Doxorubicin conjugates: a practical approach for its cardiotoxicity alleviation.

INTRODUCTION: Doxorubicin (DOX) emerges as a cornerstone in the arsenal of potent chemotherapeutic agents. Yet, the clinical deployment of DOX is tarnished by its proclivity to induce severe cardiotoxic effects, culminating in heart failure and other consequential morbidities. In response, a panoply of strategies has undergone rigorous exploration over recent decades, all aimed at attenuating DOX's cardiotoxic impact. The advent of encapsulating DOX within lipidic or polymeric nanocarriers has yielded a dual triumph, augmenting DOX's therapeutic efficacy while mitigating its deleterious side effects. AREAS COVERED: Recent strides have spotlighted the emergence of DOX conjugates as particularly auspicious avenues for ameliorating DOX-induced cardiotoxicity. These conjugates entail the fusion of DOX through physical or chemical bonds with diminutive natural or synthetic moieties, polymers, biomolecules, and nanoparticles. This spectrum encompasses interventions that impinge upon DOX's cardiotoxic mechanism, modulate cellular uptake and localization, confer antioxidative properties, or refine cellular targeting. EXPERT OPINION: The endorsement of DOX conjugates as a compelling stratagem to mitigate DOX-induced cardiotoxicity resounds from this exegesis, amplifying safety margins and the therapeutic profile of this venerated chemotherapeutic agent. Within this ambit, DOX conjugates stand as a beacon of promise in the perpetual pursuit of refining chemotherapy-induced cardiac compromise.

Biological evaluation of combinations of tyrosine kinase inhibitors with Inecalcitol as novel treatments for human chronic myeloid leukemia.

Background: The use of tyrosine kinase inhibitors (TKIs) as a treatment for chronic myeloid leukemia (CML) has improved the natural history of the disease and increased the duration of survival. Tyrosine kinase inhibitors represent the success of target therapies that work on molecular targets, although some patients still have therapy failure. Vitamin D has antiproliferative, pro-apoptotic, and anti-angiogenic effects on cells, therefore it can be considered as a potential cancer preventative and treatment agent. Inecalcitol (TX-522) is the 14-epi-analogue of Calcitriol (1,25(OH)2-vitamin D3), and inhibits cancer cell proliferation more effectively than Calcitriol. This study was conducted to evaluate the antiproliferative and synergistic effects of the anticancer drugs Imatinib and Dasatinib in combinations with Inecalcitol on human chronic myeloid leukemia K-562 cells. Method: The growth inhibitory activities of Inecalcitol, Imatinib, Dasatinib, and different combinations of one of the two drugs (Imatinib and Dasatinib) with Inecalcitol, were determined in vitro using MTT assay against K-562 cell line. Results: Inecalcitol, Imatinib, and Dasatinib showed potent antiproliferative activities against K-562 cells with GI50 values of 5.6 µM, 0.327 µM, and 0.446 nM, respectively. Combinations of Imatinib or Dasatinib with different concentrations of Inecalcitol increased significantly the antiproliferative activities and potencies of both drugs (****p < 0.0001), with optimal GI50 values of 580 pM (Imatinib) and 0.51 pM (Dasatinib). Furthermore, the combination treatments showed synergistic interaction between the antileukemic drugs and Inecalcitol, with combination indices (CI) < 1. Conclusion: The study demonstrated that the human chronic myeloid leukemia K-562 cells were subjected to a synergistic growth inhibitory impact when antileukemic drugs (Imatinib or Dasatinib) were combined with Inecalcitol, therefore, it is recommended that these combinations be viewed as promising novel antileukemic medications and used in place of individual medications with lower dosages and negligible side effects in the treatment of CML.

Synthesis and biological evaluation of novel 2-morpholino-4-anilinoquinoline derivatives as antitumor agents against HepG2 cell line.

Cancer is a life-threatening illness all over the world, and developing anticancer treatments with high efficacy and low side effects remains a challenge. The quinoline ring structure has long been recognized as a flexible nucleus in the design and synthesis of physiologically active chemicals. In this study, five new 2-morpholino-4-anilinoquinoline compounds were synthesized and their biological anticancer potential against the HepG2 cell line was assessed. The compounds produced demonstrated varying responses against HepG2 cells, with compounds 3c, 3d, and 3e exhibiting the highest activity, with IC50 values of 11.42, 8.50, and 12.76 µM, respectively. It is a critical requirement that anticancer medications are able to selectively decrease cancer growth while not causing damage to normal cells. Compound 3e exhibited increased activity while maintaining adequate selectivity. It was also the most effective chemical against cell migration and adhesion, which could play an important role in drug resistance and cell metastasis. In total, the findings revealed good possibilities for anticancer therapy, suggesting a target for future development of anticancer medication.

Biological Performance of Primary Dental Pulp Stem Cells Treated with Gold Nanoparticles.

Gold nanoparticles (AuNPs) are one of the most stable nanoparticles that have been prevalently used as examples for biological and biomedical applications. Herein, we evaluate the effect of AuNPs on the biological processes of dental pulp stem cells derived from exfoliated deciduous teeth (SHED). Two different shapes of PEGylated AuNPs, rods (AuNR-PEG) and spheres (AuNS-PEG), were prepared and characterized. SHED cells were treated with different concentrations of AuNR-PEG and AuNS-PEG to determine their effect on the stemness profile of stem cells (SCs), proliferation, cytotoxicity, cellular uptake, and reactive oxygen species (ROS), for cells cultured in media containing-fetal bovine serum (FBS) and serum-free media (SFM). Our results showed that both nanoparticle shapes maintained the expression profile of MSC surface markers. Moreover, AuNS-PEG showed a stimulatory effect on the proliferation rate and lower toxicity on SHED, compared to AuNR-PEG. Higher concentrations of 0.5-0.125 nM of AuNR-PEG have been demonstrated to cause more toxicity in cells. Additionally, cells treated with AuNPs and cultured in FBS showed a higher proliferative rate and lower toxicity when compared to the SFM. For cellular uptake, both AuNS-PEG and AuNR-PEG were uptaken by treated cells efficiently. However, cells cultured in SFM media showed a higher percentage of cellular uptake. For ROS, AuNR-PEG showed a significant reduction in ROS at lower concentrations (<0.03 nM), while AuNS-PEG did not show any significant difference compared to the control untreated cells. Thus, our results give evidence about the optimum concentration and shape of AuNPs that can be used for the differentiation of stem cells into specific cell lineages in tissue engineering and regenerative medicine.

Effective Generation of Functional Pancreatic ß Cells from Human-Derived Dental Stem Cells of Apical Papilla and Bone-Marrow-Derived Stem Cells: A Comparative Study.

Diabetes Mellitus Type 1 is an autoimmune disease that occurs due to the destruction of insulin-producing cells (ß cells), resulting in hyperglycemia. Therefore, diabetic patients depend on insulin treatment for the rest of their lives. Stem cells are considered a promising cellular therapy to replace the nonfunctional beta cells with functional and mature beta cells. Hence, in this study, we aimed to examine the potential of dental stem cells of apical papilla (SCAP) to differentiate into functional islet cell aggregates (ICAs), compared to the ICA generated from bone-marrow-derived stem cells (BM-MSCs). Our strategy was to induce the differentiation of SCAP and BM-MSCs into a definitive endoderm. The success of endodermal differentiation was determined by measuring the expression of definitive endodermal markers, FOXA2 and SOX-17, by flow cytometry. Next, the maturity and functionality of the differentiated cells were evaluated by measuring the amount of insulin and C-peptide secreted by the derived ICAs using ELISA. Additionally, the expression of mature beta cell markers-insulin, C-peptide, glucagon and PDX-1-was detected through confocal microscopy, while the staining of the mature islet-like clusters was detected by using diphenythiocarbazone (DTZ). Our results have shown that both SCAP and BM-MSCs were sequentially committed to a definitive pancreatic endoderm and ß-cell-like cells by upregulating the expression of FOXA2 and SOX17 significantly (**** p < 0.0000 and *** p = 0.0001), respectively. Moreover, the identity of ICAs was confirmed by DTZ-positive staining, as well as by the expression of C-peptide, Pdx-1, insulin and glucagon at day 14. It was noted that at day 14, differentiated ICAs released insulin and C-peptides in a significant manner (* p < 0.01, *** p = 0.0001), respectively, exhibiting in vitro functionality. Our results demonstrated for the first time that SCAP could be differentiated into pancreatic cell lineage in a similar manner to BM-MSCs, suggesting a new unambiguous and nonconventional source of stem cells that could be used for stem cell therapy to treat diabetes.

1,4-Naphthoquinone Induces FcRn Protein Expression and Albumin Recycling in Human THP-1 Cells.

The neonatal Fc receptor (FcRn) has been established as a major factor in regulating the metabolism of albumin and IgG in humans by protecting them from intracellular degradation after they are endocytosed into cells. We assume that increasing the levels of endogenous FcRn proteins in cells would be beneficial to enhance the recycling of these molecules. In this study, we identify the compound 1,4-naphthoquinone as an efficient stimulator of FcRn protein expression in human THP-1 monocytic cells with potency at the submicromolar range. Also, the compound increased the subcellular localization of FcRn to the endocytic recycling compartment and enhanced human serum albumin recycling in the PMA-induced THP-1 cells. These results suggest that 1,4-naphthoquinone stimulates FcRn expression and activity in human monocytic cells in vitro and it could open a new avenue for designing cotreatment agents to enhance the efficacy of biological treatments such as albumin-conjugated drugs in vivo.

The Osteogenic Role of Biomaterials Combined with Human-Derived Dental Stem Cells in Bone Tissue Regeneration.

The use of stem cells in regenerative medicine had great potential for clinical applications. However, cell delivery strategies have critical importance in stimulating the differentiation of stem cells and enhancing their potential to regenerate damaged tissues. Different strategies have been used to investigate the osteogenic potential of dental stem cells in conjunction with biomaterials through in vitro and in vivo studies. Osteogenesis has a broad implication in regenerative medicine, particularly for maxillofacial defects. This review summarizes some of the most recent developments in the field of tissue engineering using dental stem cells.

The Immunomodulatory and Regenerative Effect of Biodentine™ on Human THP-1 Cells and Dental Pulp Stem Cells: In Vitro Study.

Background: Pulp tissue affected by deep caries and trauma can be protected by vital pulp therapies in which pulp regeneration success depends on the degree of pulp inflammation and the presence of regenerative signals. Reparative dentinogenesis requires dental pulp stem cell (DPSC) activity which can be stimulated by many bioactive molecules to repair the dentine, mediating a balance between the inflammatory response and the reparative events. Therefore, this study was performed in order to investigate the immune-inflammatory effect of Biodentine capping material on DPSCs and macrophages. Method: THP-1, a human monocytic cell line, was differentiated to macrophages, and flow cytometry was used to analyze the expressions of specific macrophage markers. LPS-mediated infection was created for macrophages and DPSCs followed by treatment with Biodentine. CBA array was used to investigate the cytokine secretion followed by qPCR. Migration potential of treated DPSCs was also determined. Results: Our results showed that THP-1 cell line was successfully differentiated into macrophages as shown by surface marker expression. CBA array and qPCR results showed that Biodentine-treated DPSCs and macrophages upregulated anti-inflammatory cytokines and downregulated proinflammatory cytokines. Also, Biodentine enhances the migration potential of treated DPSCs. Conclusion: Biodentine capping material mediated the polarization of M1 to M2 macrophages suggestive of tissue repair properties of macrophages and enhanced the anti-inflammatory cytokines of DPSCs responsible for dentine-pulp regeneration.

The In Vitro Immunomodulatory Effects of Gold Nanocomplex on THP-1-Derived Macrophages.

Introduction: This study is aimed at investigating the immunological response after treating THP-1 cells with gold nanorods conjugated with a phosphatidylinositol 3-kinase (PI3Kα) inhibitor. Methodology. Gold nanorods were synthesized and functionalized with cholesterol-PEG-SH moiety, and the treatment groups were as follows: nanocomplex (a drug-conjugated gold nanorods), free drug (phosphatidylinositol 3-kinase (PI3Kα) inhibitor), and GNR (the nanocarrier; cholesterol-coated gold nanorods). THP-1 cells were differentiated into macrophages and characterized by measuring the expression of macrophage surface markers by flow cytometry. Then, differentiated cells were activated by lipopolysaccharide (LPS). Afterwards, activated macrophages were treated with the different treatments: nanocomplex, free drug, and GNR, for 24 hrs. After treatment, the production of the inflammatory cytokines measured at gene and protein levels by using qPCR and CBA array beads by flow cytometry. Results: Our results show that THP-1 cells were successfully differentiated into macrophages. For inflammatory cytokine expression response, nanocomplex and free drug showed the same expression level of cytokines at gene level, as the expression of IL-1ß, IL-6, and TNF-α was significantly downregulated (p < 0.0005, p < 0.0005, p < 0.00005), respectively, while IL-8, IL-10, and TGF-ß were all upregulated in a significant manner for nanocomplex (p < 0.00005, p < 0.00005, p < 0.00005) and free drug treatment group (p < 0.00005, p < 0.05, p < 0.05) compared to the control untreated group. While in the GNR group, IL-6 and TNF-α were downregulated (p < 0.005, p < 0.00005), and IL-12p40 (p < 0.00005) was upregulated all in a statistically significant manner. While at protein level, cells were treated with our nanocomplex: IL-1ß, IL-6, TNF-α, and IL-12p70 and were significantly decreased (p < 0.00005,p < 0.005,p < 0.05,p < 0.00005), and IL-10 was found to be significantly increased in culture compared to the untreated control group (p < 0.005). For free drug; IL-1ß and IL-12p70 were significantly decreased (p < 0.00005, p < 0.00005), while a significant increase in the secretion levels of IL-10 only was noticed compared to the untreated group (p < 0.005). For GNR treatment groups, IL-1ß, TNF-α, and IL-12p70 were significantly decreased (p < 0.00005, p < 0.05, p < 0.00005). Conclusion: We can conclude that our nanocomplex is a potent effector that prevents tumoral progression by activating three main immunological strategies: switching the surface expression profile of the activated macrophages into a proinflammatory M1-like phenotype, downregulating the expression of proinflammatory cytokines, and upregulating the expression level of anti-inflammatory cytokines.

In Vitro Anticancer Properties of Novel Bis-Triazoles.

Here, we describe the anticancer activity of our novel bis-triazoles MS47 and MS49, developed previously as G-quadruplex stabilizers, focusing specifically upon the human melanoma MDA-MB-435 cell line. At the National Cancer Institute (NCI), USA, bis-triazole MS47 (NCS 778438) was evaluated against a panel of sixty human cancer cell lines, and showed selective, distinct multi-log differential patterns of activity, with GI50 and LC50 values in the sub-micromolar range against human cancer cells. MS47 showed highly selective cytotoxicity towards human melanoma, ovarian, CNS and colon cancer cell lines; in contrast, the leukemia cell lines interestingly showed resistance to MS47 cytotoxic activity. Further studies revealed the potent cell growth inhibiting properties of MS47 and MS49 against the human melanoma MDA-MB-435 cell line, as verified by MTT assays; both ligands were more potent against cancer cells than MRC-5 fetal lung fibroblasts (SI > 9). Melanoma colony formation was significantly suppressed by MS47 and MS49, and time- and dose-dependent apoptosis induction was also observed. Furthermore, MS47 significantly arrested melanoma cells at the G0/G1 cell cycle phase. While the expression levels of Hsp90 protein in melanoma cells were significantly decreased by MS49, corroborating its binding to the G4-DNA promoter of the Hsp90 gene. Both ligands failed to induce senescence in the human melanoma cells after 72 h of treatment, corroborating their weak stabilization of the telomeric G4-DNA.

1,4-Naphthoquinone Is a Potent Inhibitor of IRAK1 Kinases and the Production of Inflammatory Cytokines in THP-1 Differentiated Macrophages.

Quinones are a class of cyclic organic compounds that are widely distributed in nature and have been shown to exhibit anti-inflammatory, antioxidant, and anticancerous activities. However, the molecular mechanisms/signaling by which these molecules exert their effect are still not fully understood. In this study, a group of quinone-derived compounds were examined for their potential inhibitory effect against human IRAK1 and IRAK4 kinases in vitro. We have identified five compounds: 1,4-naphthoquinone, emodin, shikonin, plumbagin, and menadione (vitamin K3) as active and selective inhibitors of human IRAK1 enzyme in vitro. The biochemical binding and molecular interactions between the active compounds and IRAK1's catalytic site were demonstrated in silico using structural-based docking and dynamic simulation analysis. Also, 1,4-naphthoquinone was found to effectively inhibit the growth of cancer cell lines overexpressing IRAK1. Furthermore, 1,4-naphthoquinone potently suppressed the production and secretion of key proinflammatory cytokine proteins IL-8, IL-1ß, IL-10, TNF-α, and IL-6 in LPS-stimulated PMA-induced human THP-1 macrophages. In conclusion, 1,4-naphthoquinone is an effective inhibitor of IRAK1 kinases and their mediated inflammatory cytokines production in LPS-stimulated PMA-induced human THP-1 macrophages.

An In Vitro Comparison of Anti-Tumoral Potential of Wharton's Jelly and Bone Marrow Mesenchymal Stem Cells Exhibited by Cell Cycle Arrest in Glioma Cells (U87MG).

The therapeutic potential of mesenchymal stem cells (MSCs) for various malignancies is currently under investigation due to their unique properties. However, many discrepancies regarding their anti-tumoral or pro-tumoral properties have raised uncertainty about their application for anti-cancer therapies. To investigate, if the anti-tumoral or pro-tumoral properties are subjective to the type of MSCs under different experimental conditions we set out these experiments. Three treatments namely cell lysates (CL), serum-free conditioned media and FBS conditioned media (FBSCM) from each of Wharton's Jelly MSCs and Bone Marrow-MSCs were applied to evaluate the anti-tumoral or pro-tumoral effect on the glioma cells (U87MG). The functional analysis included; Morphological evaluation, proliferation and migration potential, cell cycle analysis, and apoptosis for glioma cells. The fibroblast cell line was added to investigate the stimulatory or inhibitory effect of treatments on the proliferation of the normal cell. We found that cell lysates induced a generalized inhibitory effect on the proliferation of the glioma cells and the fibroblasts from both types of MSCs. Similarly, both types of conditioned media from two types of MSCs exerted the same inhibitory effect on the proliferation of the glioma cells. However, the effect of two types of conditioned media on the proliferation of fibroblasts was stimulatory from BM-MSCs and variable from WJ-MSCs. Moreover, all three treatments exerted a likewise inhibitory effect on the migration potential of the glioma cells. Furthermore, we found that the cell cycle was arrested significantly at the G1 phase after treating cells with conditioned media which may have led to inhibit the proliferative and migratory abilities of the glioma cells (U87MG). We conclude that cell extracts of MSCs in the form of secretome can induce specific anti-tumoral properties in serum-free conditions for the glioma cells particularly the WJ-MSCs and the effect is mediated by the cell cycle arrest at the G1 phase.

Cytotoxicity and Cellular Death Modality of Surface-Decorated Gold Nanorods against a Panel of Breast Cancer Cell Lines.

Herein, the antiproliferative effect of surface-decorated gold nanorods (GNRs) was investigated against three different breast cancer cell lines. The results indicate that the cell lines exhibited different biological responses and death modalities toward the treatment. The cell lines exhibited similar cellular uptake of the nanoparticles; however, MDA-MB-231 demonstrated the highest cytotoxicity compared to other cell lines upon treatment with GNRs. The expression of the CDH1 gene, which is involved in cell adhesion and metastasis, was dramatically increased in treated MDA-MB-231 cells compared to other cell lines. Early apoptosis and late apoptosis are the dominant cellular death modalities of MDA-MB-231 cells upon treatment with GNRs.

Anti-oncogenic activities exhibited by paracrine factors of MSCs can be mediated by modulation of KITLG and DKK1 genes in glioma SCs in vitro.

Cancer stem cells (CSCs) use their stemness properties to perpetuate their lineage and survive chemotherapy. Currently cell-based and cell-free therapies are under investigation to develop novel anti-cancer treatment modalities. We designed this study to investigate how cell extracts of mesenchymal stem cells affect the growth of glioma stem cells in vitro. Gliospheres were generated from the U87MG cell line and treated with conditioned media of Wharton's jelly and bone marrow mesenchymal stem cells. The effects were investigated at the functional and molecular levels. Our results showed that conditioned media from both types of mesenchymal stem cells changed the morphology of spheres and inhibited the proliferation, invasion, and self-renewal ability of glioma stem cells. At the molecular level, metabolism interruption at oxidative phosphorylation, cell cycle arrest, cell differentiation, and upregulation of the immune response were observed. Furthermore, this effect was mediated by the upregulation of the DKK1 gene inhibiting the Wnt pathway mediated by growth factor activity and downregulation of the KITLG gene activated by growth factor and cytokine activity, inhibiting multiple pathways. We conclude that different types of mesenchymal stem cells possess antitumor properties and their paracrine factors, in combination with anti-immune modalities, can provide practical therapeutic targets for glioblastoma treatment.

Derivation of three human induced pluripotent stem cell lines (JUCTCi014-A, JUCTCi015-A, JUCTCi016-A) from mesenchymal stem cells (MSCs) derived from bone marrow, adipose tissue and Wharton's jelly samples.

Mesenchymal stem cells (MSCs) are recognized as a valuable source of cells in clinical treatment and tissue engineering applications. In this study, we created human induced pluripotent stem cells (hiPSCs) from different MSC sources to evaluate the capacity of MSC-derived iPSCs to differentiate into any cell type of the human body and to serve as an alternative source for iPSC generation. Here in, the generated hiPSC lines retained their normal karyotype and showed similar STR-based identities to the parental cells. Reprogrammed cells also showed positive expression of the pluripotency markers and the ability to differentiate into the three germ layers.

Generation and characterization of induced pluripotent stem cell (iPSC) line (JUCTCi002-A) from a patient with ataxia with oculomotor apraxia type 1 (AOA1) harboring a homozygous mutation in the APTX gene.

Ataxia with Oculomotor Apraxia Type 1 (AOA1) is an autosomal-recessive cerebellar ataxia characterized by early-onset cerebellar atrophy and axonal sensorimotor polyneuropathy. AOA1 is related to mutations in the aprataxin (APTX) gene encoding for the aprataxin protein. The aprataxin protein has been reported to be involved in DNA single-strand break repair (SSBR) machinery and it localizes to the mitochondria to preserve the mitochondrial function. Here, we demonstrate the generation of induced pluripotent stem cell (iPSC) line (JUCTCi002-A) from AOA1 patient's skin dermal fibroblasts. The selected line showed normal karyotype, expression of pluripotency markers and the ability to differentiatie in vitro into the three germ layers.

Neuro-regenerative potential of dental stem cells: a concise review.

This review will summarize the research information regarding the regenerative potential of dental stem cells for the treatment of neurodegenerative disorders. As compared to existing treatment modalities, the stem cell therapy seems promising, and accumulating evidences about the differentiation of stem cells into various lineages are proving it. The incidence of neurodegenerative diseases such as Alzheimer's, Parkinson's, stroke, and peripheral neuropathy is increasing due to the rise in life expectancies of people which have put a huge burden on economies. Finding a promising treatment could benefit not only the patients but also the communities. Dental stem cells hold a great potential to differentiate into neuronal cells. Many studies have reported the differentiation potential of the dental stem cells with the presence of neuronal lineage markers. In this review, we conferred how the use of dental stem cells can benefit the above-mentioned bedridden diseases.

Establishment of (JUCTCi007-A) iPSC line from a patient with congenital myasthenic syndrome (CMS) carrying a homozygous mutation p.Arg331Trp (c.991C > T) in the CHRNE gene.

Induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts obtained from a 24-year-old female diagnosed with hereditary congenital myasthenic syndrome (CMS), caused by p.Arg331Trp (c.991C > T) homozygous mutation in the gene coding for the epsilon subunit of the acetylcholine receptor (CHRNE). The generated iPSCs shared similar karyotype with the parental dermal fibroblast cells, expressed pluripotency stem cell markers, and demonstrated differentiation potential into the three germ layers. This cell line can be used as an ideal model to facilitate the understanding of the pathogenic disease mechanisms underlying the congenital myasthenic syndrome and for developing novel therapeutic strategies.

Establishment of a human induced pluripotent stem cell (iPSC) line (JUCTCi010-A) from a healthy Jordanian female skin dermal fibroblasts.

Human integration-free induced pluripotent pluripotent stem cells (hiPSCs) were generated from skin fibroblasts obtained from a 27-year-old healthy Jordanian female. The resulting iPSCs expressed the most common pluripotency stem cell markers, they retained the normal karyotype similar to the original fibroblasts and showed the potential to differentiate into three germ layers in vitro. This iPSC line could serve as a wild-type control that can be used in hereditary disease modeling studies and in optimization of different differentiation protocols.

Gold Nanocomplex Strongly Modulates the PI3K/Akt Pathway and Other Pathways in MCF-7 Breast Cancer Cell Line.

Conjugating drugs with gold nanoparticles (GNP) is a key strategy in cancer therapy. Herein, the potential inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, and other pathways of the MCF-7 cell-line, was investigated upon treatment with gold nanorods (GNR) conjugated with a PI3K inhibitor drug. The results revealed that the coupling of GNR with the drug drastically modulated the expression of PI3Kα at the gene and protein levels compared to the drug or GNR alone. The PI3Kα pathway is involved in tumor progression and development through the mediation of different mechanisms such as apoptosis, proliferation, and DNA damage. Treatment with the nanocomplex significantly affected the gene expression of several transcription factors responsible for cell growth and proliferation, apoptotic pathways, and cell cycle arrest. Furthermore, the gene expression of different regulatory proteins involved in cancer progression and immune responses were significantly modified upon treatment with the nanocomplex compared to the free drug or GNR alone.