Skin Cancer Cells Research Articles

Revolutionary composites of silver and zinc oxide nanoparticles from Hardwickia binata: Unleashing their potent antioxidant and anticancer properties

In the present of the study, was utilized the leaf extract of H. binata to synthesize Ag-ZnO nanocomposites. The nanocomposites were characterized using various techniques, including UV, FTIR, XRD and SEM-EDX. Nanocomposites are known for their promising properties, such as mechanical, thermal, electrical and optical characteristics, which have attracted significant attention from both academia and industry, resulting in active research in various fields. The introduction of silver (Ag) into the nanocomposites enabled them to exhibit UV light absorption at 366 nm, while the presence of zinc confirmed the peak at 431 nm. XRD analysis was carried out to determine the crystal structure and composition of the materials. The antibacterial properties of the Ag-ZnO nanocomposites were evaluated using the disc diffusion method, revealing the highest inhibition against the bacteria strain Bacillus subtilis (19 mm) compared to other strains. Furthermore, the nanocomposites demonstrated strong antioxidant activity against DPPH (56%), ABTS (59%) and exhibited anti-inflammatory activity (62%). Additionally, the Ag-ZnO nanocomposites showed promising anti-cancer properties, as evidenced by their effectiveness against a skin cancer cell line (A431-69%). Moreover, the nanocomposites displayed significant photocatalytic activity, resulting in a 70% degradation rate. Overall, this study successfully synthesized Ag-ZnO nanocomposites that exhibited robust antibacterial, antioxidant, anti-inflammatory and anticancer properties. These findings suggest the potential application of these nanocomposites in cancer treatment and environmental studies, particularly in dye degradation.

Microwave-assisted synthesis of novel Ti/BTB-MOFs as porous anticancer and antibacterial agents.

Nano compounds, especially metal-organic frameworks (MOFs), have significant properties. Among the most important properties of these compounds, which depend on their specific surface area and porosity, are biological properties, such as anticancer and antibacterial properties. In this study, a new titanium/BTB metal-organic framework (Ti/BTB-MOF) was synthesized by using titanium nitrate and 1,3,5-Tris(4-carboxyphenyl)benzene (BTB) under microwave radiation. The structure of the synthesized Ti/BTB-MOF was characterized and confirmed using X-ray diffraction (XRD) patterns, X-ray photoelectron spectroscopy (XPS) analysis, Fourier transform infrared (FT-IR) spectra, energy-dispersive X-ray (EDAX) analysis mapping, scanning electron microscope (SEM) images, thermogravimetric analysis (TGA) curves, and Brunauer-Emmett-Teller (BET) analysis. The in vitro anticancer properties of Ti/BTB-MOF were evaluated using the MTT method against MG-63/bone cancer cells and A-431/skin cancer cells. The in vitro antibacterial activity was tested using the Clinical and Laboratory Standards Institute (CLSI) guidelines. In the anticancer activity, IC50 (half-maximal inhibitory concentration) values of 152μg/mL and 201μg/mL for MG-63/bone cancer cells and A-431/skin cancer cells, respectively, were observed. In the antibacterial activity, minimum inhibitory concentrations (MICs) of 2-64μg/mL were observed against studied pathogenic strains. The antimicrobial activity of Ti/BTB-MOF was higher than that of penicillin and gentamicin. Therefore, the synthesized Ti/BTB-MOF could be introduced as a suitable bioactive candidate.

Bortezomib exerts its anti-cancer activity through the regulation of Skp2/p53 axis in non-melanoma skin cancer cells and C. elegans

Non-melanoma skin cancer (NMSC), encompassing basal and squamous cell carcinoma, is the most prevalent cancer in the United States. While surgical removal remains the conventional therapy with a 95% 5-year cure rate, there is a growing interest in exploring alternative treatment strategies. In this study, we investigated the role of Bortezomib (BTZ), a proteasome inhibitor, in NMSC. Using two NMSC cell lines (A431 and A388), we examined the effects of BTZ treatment. Our results demonstrated that 48 h of BTZ treatment led to downregulating Skp2 expression in both A431 and A388 cells while upregulating p53 expression, specifically in A388 cells. These alterations resulted in impaired cellular growth and caspase-dependent cell death. Silencing Skp2 in A388 cells with siRNA confirmed the upregulation of p53 as a direct target. Furthermore, BTZ treatment increased the Bax to Bcl-2 ratio, promoting mitochondrial permeability and the subsequent release of cytochrome C, thereby activating caspases. We also found that BTZ exerted its antitumor effects by generating reactive oxygen species (ROS), as blocking ROS production significantly reduced BTZ-induced apoptotic cell death. Interestingly, BTZ treatment induced autophagy, which is evident from the increased expression of microtubule-associated proteins nucleoporin p62 and LC-3A/B. In addition to cell lines, we assessed the impact of BTZ in an in vivo setting using Caenorhabditis elegans (C. elegans). Our findings demonstrated that BTZ induced germline apoptosis in worms even at low concentrations. Notably, this increased apoptosis was mediated through the activity of CEP-1, the worm’s counterpart to mammalian p53. In summary, our study elucidated the molecular mechanism underlying BTZ-induced apoptosis in NMSC cell lines and C. elegans. By targeting the skp2/p53 axis, inducing mitochondrial permeability, generating ROS, and promoting autophagy, BTZ demonstrates promising anti-cancer activity in NMSC. These findings provide novel insights into potential therapeutic strategies for controlling the unregulated growth of NMSC.

Alginate Nanoparticles Containing Cuminum cyminum and Zataria multiflora Essential Oils with Promising Anticancer and Antibacterial Effects.

Cancer and bacterial infections are major global health concerns driving the need for innovative medicines. This study investigated alginate nanoparticles loaded with essential oils (EOs) from Cuminum cyminum and Zataria multiflora as potential drug delivery systems. The nanoparticles were comprehensively characterized using techniques such as gas chromatography-mass spectrometry (GC-MS), dynamic light scattering (DLS), zetasizer, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and ultraviolet-visible spectroscopy (UV-Vis). Their biological properties against two human skin cancer cell lines (A-375 and A-431) and three bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) were also evaluated. Alginate nanoparticles containing C. cyminum and Z. multiflora EOs exhibited sizes of 160 ± 8 nm and 151 ± 10 nm, respectively. Their zeta potentials and encapsulation efficiencies were -18 ± 1 mV and 79 ± 4%, as well as -27 ± 2 mV and 86 ± 5%, respectively. The IC50 values against the tested cell lines and bacteria revealed superior efficacy for nanoparticles containing Z. multiflora EO. Considering the proper efficacy of the proposed nanoparticles, the straightforward preparation method and low cost suggest their potential for further in vivo studies.

Fagopyrin F fraction from Fagopyrum tataricum demonstrates photodynamic inactivation of skin infecting bacterium and squamous cell carcinoma (A431) cells.

Photodynamic therapy (PDT) stands out as a noteworthy development as an alternative targeted treatment against skin ailments. While PDT has advanced significantly, research into photo-activatable "Green drugs" derived from plants which are less toxic than the synthetic drugs has not kept pace. This study investigates the potential of Fagopyrin F Containing Fraction (FCF) derived from Fagopyrum tataricum in mediating PDT against Staphylococcus aureus and skin cancer cells (A431). FCF was isolated from the plant extract using thin-layer chromatography, followed by identification of the compound through high-performance liquid chromatography and high-resolution liquid chromatography-mass spectrometry. FCF was tested to determine its antibacterial and anticancer efficacy. Results revealed that FCF-mediated PDT exhibited potent action against S. aureus, significantly reducing bacterial viability (MIC 19.5 μg/100 μL). Moreover, FCF-mediated PDT showed good efficacy against A431 cells, resulting in a notable reduction in cell viability (IC50 29.08μg/mL). Given the known association between S. aureus and squamous cell carcinoma (SCC), FCF shows the potential to effectively target and eradicate both SCC and the related S. aureus present within the lesions. In silico study reveals that Fagopyrin F effectively binds with the epidermal growth factor (EGFR), one among the highly expressed proteins in the A431 cells, with a binding energy of -9.6kcal/mol. The affinity of Fagopyrin F for EGFR on A431 cancer cells along with its cytotoxicity against skin cancer cells while safeguarding the normal cells (L929) plays a major part in the way it targets cancer cells. However, its safety, efficacy, and long-term advantages in treating skin conditions require more investigation, including in vivo investigations and clinical trials.

Superior Drug Delivery Performance of Multifunctional Bilosomes: Innovative Strategy to Kill Skin Cancer Cells for Nanomedicine Application.

Numerous failures in melanoma treatment as a highly aggressive form of skin cancer with an unfavorable prognosis and excessive resistance to conventional therapies are prompting an urgent search for more effective therapeutic tools. Consequently, to increase the treatment efficiency and to reduce the side effects of traditional administration ways, herein, it has become crucial to combine photodynamic therapy as a promising therapeutic approach with the selectivity and biocompatibility of a novel colloidal transdermal nanoplatform for effective delivery of hybrid cargo with synergistic effects on melanoma cells. The self-assembled bilosomes, co-stabilized with L-α-phosphatidylcholine, sodium cholate, Pluronic® P123, and cholesterol, were designated, and the stability of colloidal vesicles was studied using dynamic and electrophoretic light scattering, also provided in cell culture medium (Dulbecco's Modified Eagle's Medium). The hybrid compounds - a classical photosensitizer (Methylene Blue) along with a complementary natural polyphenolic agent (curcumin), were successfully co-loaded, as confirmed by UV-Vis, ATR-FTIR, and fluorescent spectroscopies. The biocompatibility and usefulness of the polymer functionalized bilosome with loaded double cargo were demonstrated in vitro cyto- and phototoxicity experiments using normal keratinocytes and melanoma cancer cells. Thein vitrobioimaging and immunofluorescence study upon human skin epithelial (A375) and malignant (Me45) melanoma cell lines established the protective effect of the PEGylated bilosome surface. This effect was confirmed in cytotoxicity experiments, also determined on human cutaneous (HaCaT) keratinocytes. The flow cytometry experiments indicated the enhanced uptake of the encapsulated hybrid cargo compared to the non-loaded MB and CUR molecules, as well as a selectivity of the obtained nanocarriers upon tumor cell lines. The phyto-photodynamic action provided 24h-post irradiation revealed a more significant influence of the nanoplatform on Me45 cells in contrast to the A375 cell line, causing the cell viability rate below 20% of the control. As a result, we established an innovative and effective strategy for potential metastatic melanoma treatment through the synergism of phyto-photodynamic therapy and novel bilosomal-origin nanophotosensitizers.

Co-Administration of Chemo-Phototherapeutic Loaded Lignin Nanoarchitecture for the Treatment of Skin Cancer Cell Lines and Bacterial Infections

Co-Administration of Chemo-Phototherapeutic Loaded Lignin Nanoarchitecture for the Treatment of Skin Cancer Cell Lines and Bacterial Infections

Cold atmospheric plasma attenuates skin cancer via ROS induced apoptosis.

Cold atmospheric plasma (CAP) has been widely used in biomedical research, especially in vitro cancer therapy. Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor originating from epidermal keratinocytes. However, the mechanism of CAP therapy on CSCC remains unclear. The animal models of CSCC induced by 7,12-dimethylbenz(a) anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) were constructed. For the CAP treatment group, after each TPA application, CAP was administered for 3min twice weekly after drying. HE staining were used to detect the pathological status of tumor tissue in each group. The levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 were evaluated by western blot and qPCR. TUNEL staining were used to detect apoptosis in tumor tissues. In vivo, serum samples were used for ELISA of total ROS. MTT assay was used to detect the viability of A431 cells. Western blot and qPCR were used to detect the levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 in A431 cells. A431 cell proliferation was examined by colony formation assay. The proportions of apoptosis of A431 cells were detected by flow cytometry. Transwell assessed the ability of A431 cells migration and proliferation. We found that CAP could induce skin cancer cells apoptosis and inhibit the progress of skin cancer. Through experiments in vitro, reactive oxygen species (ROS) generated by N-acetylcysteine (NAC) and CAP inhibited the proliferation and migration of A431 skin cancer cells while promoting apoptosis. These evidences suggest the protective effect of CAP in CSCC, and CAP has the potential clinical application of CSCC.

Abstract LB431: Direct comparison of focal adhesion kinase (FAK) therapeutic modalities in cancer: Kinase, FAT, and PROTAC

Abstract Introduction: Focal Adhesion Kinase (FAK) is a multifunctional non-receptor tyrosine kinase and scaffolding protein that has emerged as a potential therapeutic target for the treatment of cancer due to its upregulation and role in cancer cell survival. However, it remains unknown which cancer types are most susceptible to FAK modulation or the best pharmacological strategy to target FAK. FAK is endogenously regulated by an alternative transcript termed FAK-related non-kinase (FRNK), which inhibits FAK through the Focal Adhesion Targeting (FAT) domain. Current FAK-kinase inhibitors that block the catalytic site have shown limited efficacy in multiple Phase I/II clinical trials. FAK-degrading PROTACs have also shown inadequate induction of antiproliferative effects despite successful protein degradation. However, we have shown promising results with our novel FAK-FAT inhibitors, which target the scaffolding function of FAK to induce anoikis and inhibit proliferation in cancer cells. A direct comparison of these different FAK modulators in various cancer types has yet to be performed, creating a significant gap in understanding the best approach for targeted FAK inhibition for the treatment of cancer. Methods: The Broad Institute’s Cancer Dependency Map (DepMap) was utilized to select a cancer cell line cohort based on dependency on FAK for survival. Four cancer types, including breast, brain, lung, and skin cancers were selected based on the correlation of FAK expression for survival and previous literature evidence for dependency on FAK. Three FAK-dependent and one FAK-independent cell lines per cancer type were selected for a total of 16 cancer cell lines. Genetic adenoviral constructs that block the FAK-FAT domain (Ad-FRNK) and knockdown FAK levels (shRNA) were utilized to investigate the role of FAK in cancer cell survival. These constructs were used as they recapitulate the pharmacological strategy of our FAK-FAT inhibitor UA-2012 and FAK degrading PROTACs, respectively. Results: Cell viability was significantly decreased in 10/13 FAK-dependent cell lines after transduction with either adFRNK or FAK targeting shRNAs, six of which showed a statically significant decrease in cell viability upon transduction with adFRNK compared to shRNAs. No cell lines showed a greater response to FAK shRNAs compared to adFRNK. We then evaluated the ability of the FAK kinase inhibitor Defactinib, FAK degrading PROTAC BI-3663, and our novel FAK-FAT domain inhibitor UA-2012 to induce cancer cell death. Overall, FAK-FAT domain inhibition with UA-2012 resulted in the most potent reduction in viability of FAK-dependent cells, particularly in skin and breast cancer cell lines. Treatment with Defactinib resulted in low IC50 values regardless of FAK, and PROTAC BI-3663 displayed minimal effects with high IC50 values often above 200 µM despite successful protein degradation. Conclusion: This data suggests that the FAK-FAT domain may be the major modulator of FAK-mediated survival in breast and skin cancer cells. Citation Format: Lauren Reyes, Ruchi Khatiwala, Timothy Marlowe. Direct comparison of focal adhesion kinase (FAK) therapeutic modalities in cancer: Kinase, FAT, and PROTAC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB431.

Hypericin - a natural photosensitizer in photodynamic therapy on skin cancer cells

SignificanceThe aim of the study was to measure the effectiveness of hypericin in the photokilling of skin cancer cells after orange light irradiation. ApproachTests were carried out on the skin cancer cells SSC-25 and MUG-Mel2, and keratinocytes HaCaT cell line with the use of hypericin and PDT. We performed cytotoxicity tests, cellular uptake with flow cytometry, and TUNEL assay to detect apoptotic bodies. ResultsIn cytotoxicity experiments, don't observe difference in keratinocyte viability, but in cancer cells the after-viability was decreased by almost 50% after irradiation. In the TUNEL assay, the appearance of a large number of apoptotic bodies in cancer cell lines was observed. In the cellular uptake experiments, showed that the cell lines very fast uptake hypericin. ConclusionsMore studies are necessary to confirm the potential anticancer activity of hypericin and shed light on various cellular and molecular mechanisms which are behind our findings.

Application of phytochemicals in photodynamic therapy of cancer

SignificanceHerbal medicine is an important part of the health care system in many countries as they exhibit chemopreventive and chemotherapeutic effects. The combination of phytochemicals with Photodynamic therapy is a novel approach to enhancing therapeutic efficacy. ApproachWe studied the effect of various plant extracts, phytochemicals, photosensitizers and their combinations to induce cell death in the lung, breast, colon, cervical and skin cancer cells. The efficacy of the drug moieties was evaluated using viability, proliferation, and cytotoxicity studies. Detailed cell death mechanism was studied using protein expression profiling using immunofluorescence, flow cytometry, ELISA and western blotting. ResultsThe results revealed that PDT and combination therapy groups showed significant cell death in breast and lung cancer cells. Conjugation of photosensitizers with nanoparticles and phytochemicals enhanced the drug delivery and treatment outcome. ConclusionsCombination of PDT with other existing treatments or replacing the synthetic PSs with natural ones is a promising approach in the fight against cancer with improved specific cancer cell targeting.

Albumin-coated green-synthesized zinc oxide nanoflowers inhibit skin melanoma cells growth via intra-cellular oxidative stress

Zinc oxide (ZnO) has attracted a substantial interest in cancer research owing to their promising utility in cancer imaging and therapy. This study aimed to synthesized ZnO nanoflowers coated with albumin to actively target and the inhibit skin melanoma cells. We synthesized bovine serum albumin (BSA)-coated ZnO nanoflowers (BSA@ZnO NFs) and evaluated it's in vitro and in vivo therapeutic efficacy for skin cancer cells. BSA@ZnO NFs were prepared via single-step reduction method in the presence of plant extract (Heliotropium indicum) act as a capping agent, and further the successful fabrication was established by various physico-chemical characterizations, such as scanning electron microscopy (SEM), Fourier transform infra-red (FT-IR) spectroscopy, and x-rays diffraction (XRD) analysis. The fabricated BSA@ZnO NFs appeared flower like with multiple cone-shaped wings and average hydration size of 220.8 ± 12.6 nm. Further, BSA@ZnO NFs showed enhanced cellular uptake and cytocidal effects against skin cancer cells by inhibiting their growth via oxidative stress compared uncoated ZnO NFs. Moreover, BSA@ZnO NFs showed enhance biosafety, blood circulation time, tumor accumulation and in vivo tumor growth inhibition compared to ZnO NFs. In short, our findings suggesting BSA@ZnO NFs as a promising candidate for various types of cancer treatment along with chemotherapy.

New MoS2/Tegafur-Containing Pharmaceutical Formulations for Selective LED-Based Skin Cancer Photo-Chemotherapy.

Non-melanoma skin cancer (NMSC) is one of the most common types of cancer worldwide. Despite the low mortality rate, rising incidence and recurrence rates are a burden on healthcare systems. Standard treatments such as chemotherapy, radiotherapy, and surgery are either invasive or toxic to healthy tissues; therefore, new, alternative, selective treatments are needed. In this work, a combined photothermal and chemotherapeutic approach is proposed. MoS2 was used as photothermal agent. It was prepared by a liquid-phase exfoliation and intercalation method using polyvinylpyrrolidone (PVP), followed by recirculation through a custom-built high-power ultrasonication probe. After 6 h of ultrasonication treatment, the average particle size was 165 ± 170 nm. Near-infrared (NIR) irradiation assays (810 nm, 0.1 W/cm2, 30 min, 180 J/cm2) confirmed that MoS2 nanosheets can efficiently convert NIR light into heat and reach 52 °C. The therapeutic doses of MoS2 (125 µg/mL) and Tegafur (50 µg/mL) were optimized and both were simultaneously incorporated into a Carbopol hydrogel. The cells were brought into contact with the hydrogel and irradiated with a custom-built NIR LED system. In HFF-1 cells (normal human fibroblasts), the metabolic activity was 78% (above the 70% toxicity limit-ISO 10993-5:2009(E)), while in A-431 skin cancer cells, it was 28%. In addition, the MoS2 + Tegafur hydrogels led to a 1.9-fold decrease in A-431 cancer cell metabolic activity, 72 h after irradiation, in comparison to MoS2 hydrogels, indicating a combined effect of photothermal and chemotherapy.

Production and characterization of melanin pigment from black fungus Curvularia soli AS21 ON076460 assisted gamma rays for promising medical uses

Owing to the growing need for natural materials in different fields, studying melanin production from biological sources is imperative. In the current study, the extracellular melanin pigment was produced by the fungus Curvularia soli AS21 ON076460. The factors that affect the production of melanin were optimized by the Plackett-Burman design (P-BD). The effect of gamma irradiation on melanin productivity was investigated. The maximum melanin yield (3.376 mg/L) was elicited by a stimulus of gamma irradiation at 1.0 kGy. The results evoked that, Curvularia soli AS21 ON076460 melanin exhibited excellent antimicrobial activity against all tested bacteria and fungi. Klebsiella pneumoniae ATCC 13883 and P. digitatum were mostly affected by melanin registering the inhibition zone diameters of 37.51 ± 0.012 and 44.25 ± 0.214 mm, respectively. Moreover, Curvularia soli AS21 ON076460 melanin indicated a significant antiviral efficacy (77% inhibition) of Herpes simplex virus (HSV1). The melanin pigment showed antioxidant activities with IC50 of 42 ± 0.021 and 17 ± 0.02 µg/mL against DPPH and NO, respectively. Melanin had cytotoxic action against human breast cancer and skin cancer cell lines (Mcf7and A431) as well as exerting a low percentage of cell death against normal skin cell lines (Hfb4). Melanin was effective in wound management of human skin cells by 63.04 ± 1.83% compared with control (68.67 ± 1.10%). The novelty in the study is attributed to the possibility of using gamma rays as a safe method in small economic doses to stimulate melanin production from the fungi that have been isolated. In summary, melanin produced from fungi has significant biological activities that encourage its usage as a supportive medical route.

Dietary Isoeugenol Supplementation Attenuates Chronic UVB-Induced Skin Photoaging and Modulates Gut Microbiota in Mice.

Photoaging, the primary cause of skin aging damage, results from chronic ultraviolet (UV) exposure, leading to dryness and wrinkle formation. Nutritional intervention has emerged as a practical approach for preventing and addressing the effect of skin photoaging. The primary aromatic compound isolated from clove oil, isoeugenol (IE), has antibacterial, anti-inflammatory, and antioxidant qualities that work to effectively restrict skin cancer cell proliferation. This investigation delved into the advantages of IE in alleviating skin photoaging using UVB-irradiated skin fibroblasts and female SKH-1 hairless mouse models. IE alleviated UVB-induced photodamage in Hs68 dermal fibroblasts by inhibiting matrix metalloproteinase secretion and promoting extracellular matrix synthesis. In photoaged mice, dietary IE reduced wrinkles, relieved skin dryness, inhibited epidermal thickening, and prevented collagen loss. Additionally, the intestinal dysbiosis caused by prolonged UVB exposure was reduced with an IE intervention. The results of Spearman's analysis showed a strong correlation between skin photoaging and gut microbiota. Given the almost unavoidable UVB exposure in contemporary living, this research demonstrated the efficacy of dietary IE in reversing skin photoaging, presenting a promising approach to tackle concerns related to extrinsic skin aging.

Cytotoxic Dammarane-Type Triterpenoids from <i>Aglaia cucullata</i> Peel Fruit

Four triterpenoids, known as dammarane-type, dammaradienone (1), 20(S),25-epoxy-5α-dammar-20-en-3-one (2), 20(S)-5α-dammar-24-en-3α,20-diol-3-acetate (3) and 3α-acetyl-20S,24S-epoxy-25-hydroxydammarane (4), were isolated from Aglaia cucullata peel fruit. The structures of isolated compounds were identified based on their HR-TOFMS data and extensive NMR spectroscopic analysis, as well as compared with literature data. Compounds 1-4 were assessed for cytotoxic effects against HeLa cervical and B16-F10 melanoma skin cancer cells. All compounds showed moderate to weak activity against B16-F10 cancer cells, while compound 2 exhibited the strongest activity against HeLa cancer cells with IC50 of 7.10 µg/mL indicating that the existence of an epoxy moiety at the side chain increases the cytotoxicity to HeLa cells.

Biopolymeric Nanogel as a Drug Delivery System for Doxorubicin-Improved Drug Stability and Enhanced Antineoplastic Activity in Skin Cancer Cells.

In this study, doxorubicin was loaded in a chitosan-albumin nanogel with the aim of improving its stability and exploring the potential of the system in the treatment of skin cancer. Infrared spectroscopy and X-ray diffraction confirmed the encapsulation of the drug. Transmission electron microscopy revealed the spherical shape of the nanogel particles. The drug-loaded nanogel was characterized with a small diameter of 29 nm, narrow polydispersity (0.223) and positive zeta potential (+34 mV). The exposure of encapsulated doxorubicin to light (including UV irradiation and daylight) did not provoke any degradation, whereas the nonencapsulated drug was significantly degraded. In vitro studies on keratinocytes (HaCaT) and epidermoid squamous skin carcinoma cells (A-431) disclosed that the encapsulated doxorubicin was more cytotoxic on both cell lines than the pure drug was. More importantly, the cytotoxic concentration of encapsulated doxorubicin in carcinoma cells was approximately two times lower than that in keratinocytes, indicating that it would not affect them. Thus, the loading of doxorubicin into the developed chitosan-albumin nanogel definitely stabilized the drug against photodegradation and increased its antineoplastic effect on the skin cancer cell line.

New graphene-containing pharmaceutical formulations for infrared lamps-based phototherapy of skin cancer: In vitro validation and ex-vivo human skin permeation

Basal cell carcinoma (BCC) is the most common form of human cancer, and treatment usually involves surgery, with alternative strategies being needed. We propose the use of carbopol hydrogels (HG) for topical administration of nanographene oxide (GOn) and partially-reduced nanographene oxide (p-rGOn) for photothermal therapy (PTT) of BCC. GOn and p-rGOn incorporated into the HG present lateral sizes ∼200 nm, being stable for 8 months. After 20 min irradiation with an infrared (IR) photothermal therapy lamp (15.70 mW cm−2), GOn-HG increased temperature to 44.7 °C, while p-rGOn-HG reached 47.0 °C. Human skin fibroblasts (HFF-1) cultured with both hydrogels (250 μg mL−1) maintained their morphology and viability. After 20 min IR irradiation, p-rGOn HG (250 μg mL−1) completely eradicated skin cancer cells (A-431). Ex vivo human skin permeability tests showed that the materials can successfully achieve therapeutic concentrations (250 μg mL−1) inside the skin, in 2.0 h for GO HG or 0.5 h for p-rGOn HG.

Synergistic inhibitory actions of resveratrol, epigallocatechin-3-gallate, and diallyl trisulfide against skin cancer cell line A431 through mitochondrial caspase dependent pathway: a combinational drug approach.

The harmful effect of chemotherapeutic side effects has paid a way to discover a novel with curative way for skin cancer treatment. Skin cancer prevention is more viable with the use of combination of bioactive agents than using of single bioactive compounds. Present work was demonstrated to evaluate the interaction of Resveratrol (Res), Epigallocatechin-3-gallate (EGCG), and diallyl trisulfide (DATS) with each other as a binary combination on A431 cells. Nuclear fragmentation analysis of combination of bioactive agents using DAPI analysis, detection of apoptosis, analysis of cell cycle, ROS assay, antimigration assays, and western blotting were implemented to study the combination of bioactive compounds on A431 cell line. Among the selected combination EGCG + DATS had a synergetic effect reducing cellular migration, increased intercellular reactive oxygen species generation, condensation, cell phagocytosis induced by phosphatidylserine externalization, rise in sub-G1 DNA content, and S-phase were cell cycle arrest. The combinations EGCG + DATS induced apoptotic proteins in A431 cells by upregulation of proapoptotic Bax and Bad proteins, a downmodulation of anti-apoptotic proteins Bcl2 and caspases (caspase-3, and -9) activity got triggered by intrinsic pathway. The combination of EGCG + DATS showed good anticancer potential against A431 skin cancer cell line via the mitochondrial caspase dependent pathway with very strong synergism. This finding will help to produce a novel combination/chemoprevention using dietary bioactive agents (EGCG + DATS) for the treatment of skin cancer after clinical trial.

Pharmaceutical Formulations Containing Graphene and 5-Fluorouracil for Light-Emitting Diode-Based Photochemotherapy of Skin Cancer.

Nonmelanoma skin cancer (NMSC) is the most common cancer worldwide, among which 80% is basal cell carcinoma (BCC). Current therapies' low efficacy, side effects, and high recurrence highlight the need for alternative treatments. In this work, a partially reduced nanographene oxide (p-rGOn) developed in our laboratory was used. It has been achieved through a controlled reduction of nanographene oxide via UV-C irradiation that yields small nanometric particles (below 200 nm) that preserve the original water stability while acquiring high light-to-heat conversion efficiency. The latter is explained by a loss of carbon-oxygen single bonds (C-O) and the re-establishment of sp2 carbon bonds. p-rGOn was incorporated into a Carbopol hydrogel together with the anticancer drug 5-fluorouracil (5-FU) to evaluate a possible combined PTT and chemotherapeutic effect. Carbopol/p-rGOn/5-FU hydrogels were considered noncytotoxic toward normal skin cells (HFF-1). However, when A-431 skin cancer cells were exposed to NIR irradiation for 30 min in the presence of Carbopol/p-rGOn/5-FU hydrogels, almost complete eradication was achieved after 72 h, with a 90% reduction in cell number and 80% cell death of the remaining cells after a single treatment. NIR irradiation was performed with a light-emitting diode (LED) system, developed in our laboratory, which allows adjustment of applied light doses to achieve a safe and selective treatment, instead of the standard laser systems that are associated with damages in the healthy tissues in the tumor surroundings. Those are the first graphene-based materials containing pharmaceutical formulations developed for BCC phototherapy.