Constructing Silver Nanoparticles

Each year, over two million new cases of skin cancer are diagnosed, which is greater than the combined incidence of cancers of the breast, prostate, lung and colon. Therefore, prevention of skin cancer from the harmful effects of UV remains a priority area of research.

Contents

Introduction
Summary of Experimentation

Introduction

According to the “World Cancer Report,” skin cancer constitutes nearly 30% of all newly diagnosed cancer cases worldwide and incidence continues to rise at an alarming rate in the United States. Solar ultra-violet (UV) radiation, particularly its UVB component, is an established cause of skin carcinogenesis due to its ability to cause DNA damage in skin cells. If unrepaired, the DNA damage may ultimately lead to accumulation of carcinogenic mutations leading to malignant transformation of the skin cells. To protect the DNA damage, several topical sunscreen formulations have been developed and are being used for protection against UV radiation-induced skin injury and carcinogenesis. These formulations include substances (zinc oxide or titanium dioxide nanoparticles) that reflect, scatter or absorb UV radiations and thus limit its exposure to the skin cells. Even though the sunscreens in the market have high sun protection factor (SPF) potential, they have failed in limiting the UV-induced skin cancer occurrence. Moreover, the data from several studies also demonstrated that zinc oxide or titanium dioxide may cause inflammatory/toxic effects to the normal skin cells. Therefore, it is highly desirable that we develop a novel, safe and effective formulation to reduce the incidence of skin malignancy, and curb the morbidity and mortality associated with it within the US population and worldwide.

Silver has been used for centuries to prevent and treat a variety of diseases as well as in healing of skin wounds due to its excellent free radical scavenging, antimicrobial and anti-inflammatory properties. In 1990s, silver was introduced in a colloidal form (i.e. silver nanoparticles, AgNPs) in ointments that could be applied to open wounds to kill bacteria and promote wound healing through their powerful anti-bacterial and anti-inflammatory properties. AgNPs are currently being used in various medical devices, consumer products and pharmaceuticals including bandages, wound dressings and ointments. In fact, AgNPs now contribute more than a quarter to the list of the commercially available nano-based products suggesting its wide applicability and safety in human applications. In the present novel work, we have explored the efficacy of AgNPs as chemopreventive agents against UVB radiation-induced skin carcinogenesis. Our studies reveal that AgNPs are non-toxic to the human immortalized keratinocytes (HaCaT) and protects them from UVB-induced DNA damage. Our data also demonstrate that AgNPs pretreatment significantly reduces the extent of apoptosis caused by UVB radiation in HaCaT cells as well as induces G1/S phase cell-cycle arrest. Furthermore, our study reveals the higher internalization of AgNPs in UVB-irradiated cells and indicates the involvement of nucleotide excision repair (NER) genes in the repair of UVB-induced DNA damage. These are promising observations and provide compelling support for potential novel human applications of AgNPs as chemopreventive agents against UVB-induced skin carcinogenesis.

Summary of Experimentation

Each year, over two million new cases of skin cancer are diagnosed, which is greater than the combined incidence of cancers of the breast, prostate, lung and colon. Therefore, prevention of skin cancer from the harmful effects of UV remains a priority area of research. In this project, the effect of silver nanoparticles (AgNPs) on skin epidermal immortalized, non-tumorigenic keratinocytes (HaCaT) and epidermoid carcinoma skin cancer cells (A431-NS) was tested. A chemical method was successfully utilized for the production of silver nanoparticles. The effect of size and concentration of AgNPs was tested for both skin cancer therapy as well as skin cancer chemoprevention against UV-induced cell damage. Cell viability analysis via colorimetric assay indicate that AgNPs in the size range 10 nm to 100 nm and concentration range 1 mg/L to 10 mg/L are not toxic to nontumerigenic HaCaT cells but are toxic to carcinoma A431-NS cells, thereby proving the therapeutic effect of AgNPs. Furthermore, dot-blot assay results indicate that UV-B radiation causes considerable DNA damage to HaCaT cells and this damage is signi cantly reduced in the presence of AgNPs in the size range 10-40 nm, thereby proving the chemopreventive effect of AgNPs.

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Constructing Silver Nanoparticles

Each year, over two million new cases of skin cancer are diagnosed, which is greater than the combined incidence of cancers of the breast, prostate, lung and colon. Therefore, prevention of skin cancer from the harmful effects of UV remains a priority area of research.

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