Phenotypic Switching of B16F10 Melanoma Cells as a Stress Adaptation Response to Fe3O4/Salicylic Acid Nanoparticle Therapy.
30 Sep 2021-Pharmaceuticals (Multidisciplinary Digital Publishing Institute (MDPI))-Vol. 14, Iss: 10, pp 1007
TL;DR: In this paper, the authors used syngeneic model of B16F10 melanoma implanted in C57BL/6 mice to evaluate the phenotypic changes in melanoma induced by therapy with iron oxide nanoparticles functionalized with salicylic acid (SaIONs).
Abstract: Melanoma is a melanocyte-derived skin cancer that has a high heterogeneity due to its phenotypic plasticity, a trait that may explain its ability to survive in the case of physical or molecular aggression and to develop resistance to therapy. Therefore, the therapy modulation of phenotypic switching in combination with other treatment modalities could become a common approach in any future therapeutic strategy. In this paper, we used the syngeneic model of B16F10 melanoma implanted in C57BL/6 mice to evaluate the phenotypic changes in melanoma induced by therapy with iron oxide nanoparticles functionalized with salicylic acid (SaIONs). The results of this study showed that the oral administration of the SaIONs aqueous dispersion was followed by phenotypic switching to highly pigmented cells in B16F10 melanoma through a cytotoxicity-induced cell selection mechanism. The hyperpigmentation of melanoma cells by the intra- or extracellular accumulation of melanic pigment deposits was another consequence of the SaIONs therapy. Additional studies are needed to assess the reversibility of SaIONs-induced phenotypic switching and the impact of tumor hyperpigmentation on B16F10 melanoma’s progression and metastasis abilities.
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TL;DR: In this article , a review of applications of nanoparticles in skin cancer therapy is presented, focusing on melanoma and non-melanoma, which is one of the leading cancers globally.
Abstract: Skin cancer is one of leading cancers globally, divided into two major categories including melanoma and nonmelanoma. Skin cancer is a global concern with an increasing trend, hence novel therapies are essential. The local treatment strategies play a key role in skin cancer therapy. Nanoparticles (NPs) exert potential applications in medicine with huge advantages and have the ability to overcome common chemotherapy problems. Recently, NPs have been used in nanomedicine as promising drug delivery systems. They can enhance the solubility of poorly water-soluble drugs, improve pharmacokinetic properties, modify bioavailability, and reduce drug metabolism. The high-efficient, nontoxic, low-cost, and specific cancer therapy is a promising goal, which can be achieved by the development of nanotechnology. Metallic NPs (MNPs) can act as important platforms. MNPs development seeks to enhance the therapeutic efficiency of medicines through site specificity, prevention of multidrug resistance, and effective delivery of therapeutic factors. MNPs are used as potential arms in the case of cancer recognition, such as Magnetic Resonance Imaging (MRI) and colloidal mediators for magnetic hyperthermia of cancer. The applications of MNPs in the cancer treatment studies are mostly due to their potential to carry a large dose of drug, resulting in a high concentration of anticancer drugs at the target site. Therefore, off-target toxicity and suffering side effects caused by high concentration of the drug in other parts of the body are avoided. MNPs have been applied as drug carriers for the of improvement of skin cancer treatment and drug delivery. The development of MNPs improves the results of many cancer treatments. Different types of NPs, such as inorganic and organic NPs have been investigated in vitro and in vivo for the skin cancer therapy. MNPs advantages mostly include biodegradability, electrostatic charge, good biocompatibility, high drug payload, and low toxicity. However, the use of controlled-release systems stimulated by electromagnetic waves, temperature, pH, and light improves the accumulation in tumor tissues and improves therapeutic outcomes. This study (2019-2022) is aimed at reviewing applications of MNPs in the skin cancer therapy.
2 citations
TL;DR: Reducing the time to return to baseline values for hemoglobin (HGB) in rats with bleeding-induced anemia with IV or IG therapy has proven the therapeutic potential of SaIONPs in such anemias and proper use of the administration routes may modulate intrahepatic distribution and therapeutic effects of nanoparticles.
Abstract: The liver is a key organ in the pharmacokinetics of iron oxide nanoparticles (IONPs). This paper examined how the intravenous (IV) or intragastric (IG) route of administration influenced the intrahepatic distribution or therapeutic effects of IONPs. Wistar rats, some with bleeding-induced anemia, and iron oxide nanoparticles functionalized with salicylic acid (SaIONPs), with an average hydrodynamic diameter of 73 nm, compatible with rat sinusoid fenestrations, were used in this study. Light microscopy and multispectral camera analysis of Prussian blue labeled SaIONPs allowed mapping of intrahepatic nanoparticle deposits and revealed intrahepatic distribution patterns specific to each route of administration: loading of Kupffer cells and periportal hepatocytes when the IV route was used and predominant loading of hepatocytes when the IG route was used. Reducing the time to return to baseline values for hemoglobin (HGB) in rats with bleeding-induced anemia with IV or IG therapy has proven the therapeutic potential of SaIONPs in such anemias. The long-term follow-up showed that IV therapy resulted in higher HGB values. Proper use of the administration routes may modulate intrahepatic distribution and therapeutic effects of nanoparticles. These results may be beneficial in theragnosis of liver disease.
1 citations
03 Nov 2022
TL;DR: In this paper , the authors evaluated the histopathological changes induced in mouse liver by long-term intraperitoneal injection of low doses of IONPs functionalized with salicylic acid (SaIONPs).
Abstract: With a simple synthesis and easy engineering of physicochemical properties, iron oxide nanoparticles (IONPs) have become widely used in multiple biomedical applications. The study of IONPs toxicity has become an important issue, especially as the results reported so far are contradictory and range from lack of toxicity to cellular toxicity. The aim of this study was to evaluate the histopathological changes induced in mouse liver by long-term intraperitoneal injection of low doses of IONPs functionalized with salicylic acid (SaIONPs). The study was performed on C57BL/6 mice that received by intraperitoneal injection (IP), every two days, 0.6ml of SaIONPs aqueous suspension (35mg/kg body weight SaIONPs that contained 20mg/kg body weight of Fe3O4) for 28 days. The results of this study showed that the cumulative dose of 105mg/kg body weight SaIONPs (62mg/kg body weight of Fe3O4) induced histopathological changes in the subcapsular region of the mouse liver, possible by the release of salicylic acid into the peritoneal cavity. The cumulative dose of 244mg/kg body weight SaIONPs (145mg/kg body weight of Fe3O4) induced liver centrilobular necrosis, which requires the use of lower doses in biological applications. However, this may prove to be beneficial in the case of targeted accumulation of SaIONPs.
TL;DR: In this paper , the authors investigated the potential of Caffeine to enhance the cytotoxic effects of two commonly used chemotherapeutic agents, doxorubicin and oxaliplatin, on B16F10 cells.
Abstract: Caffeine is a commonly consumed psychoactive substance that has been shown to have various effects on cellular processes, including cell growth and survival. In this study, we investigated the potential of Caffeine to enhance the cytotoxic effects of two commonly used chemotherapeutic agents, doxorubicin and oxaliplatin, on B16F10 cells. We evaluated the cytotoxicity, calculated the IC50 and combination index of the medications, estimated the cell cycle of the cells, and evaluated the apoptotic and anti-apoptotic genes through gene expression analysis. Our results demonstrated that Caffeine significantly potentiated the cytotoxicity of both doxorubicin and oxaliplatin, resulting in a more significant reduction in cell viability compared to treatment with the chemotherapeutic agents alone. Additionally, Caffeine also enhanced the pro-apoptotic effects of the chemotherapeutic agents, leading to increased levels of apoptosis in the B16F10 cells. The combination of doxorubicin and oxaliplatin with Caffeine was found to be synergistic. These findings suggest that caffeine may have the potential to improve the efficacy of current chemotherapeutic regimens and may offer a novel approach to enhance cancer treatment.
References
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Abstract: Human skin is repeatedly exposed to UVR that influences the function and survival of many cell types and is regarded as the main causative factor in the induction of skin cancer. It has been traditionally believed that skin pigmentation is the most important photoprotective factor, as melanin, besides functioning as a broadband UV absorbent, has antioxidant and radical scavenging properties. Besides, many epidemiological studies have shown a lower incidence for skin cancer in individuals with darker skin compared to those with fair skin. Skin pigmentation is of great cultural and cosmetic importance, yet the role of melanin in photoprotection is still controversial. This article outlines the major acute and chronic effects of UVR on human skin, the properties of melanin, the regulation of pigmentation and its effect on skin cancer prevention.
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TL;DR: The in-depth comprehension of each of these lethal subroutines and their intercellular consequences may uncover novel therapeutic targets for the avoidance of pathogenic cell loss.
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