Rohan Muthukumar & Jonathan Sinwell
Jonathan Sinwell is a rising junior at The Overlake School in Seattle, WA.
Rohan Muthukumar is a rising senior at Providence Senior High School in Charlotte, NC.
Substantial exposure to UVB and UVA radiation from the sun is a significant problem that can result in the development of skin cancer in humans (Wakefield et al.). To combat the threat of UV radiation, sunscreens were first developed containing organic materials that absorb UV radiation for short amounts of time (Burnett et al.). Current sunscreen products utilize inorganic oxide compounds such as titanium dioxide (TiO2) and zinc oxide (ZnO) to protect against UV radiation and subsequent damage to the skin by dispersing UV radiation before it can affect the human body. The use of nanoparticles (particles between 1 and 100 nanometers in all dimensions) is optimal because they do not produce many side effects and do not decompose when exposed to the sun (Wakefield et al.). Many sunscreens producers are now looking to switch over towards nanoparticles of TiO2 and ZnO. From a cosmetic standpoint, ZnO produces a more transparent color instead of the usual white tint, making the product more appealing to consumers. Furthermore, a study done by Tyner et al. shows that TiO2 is relatively safe while possessing beneficial properties such as increased UV light attenuation. However, researchers still do not know many of the properties of these nanomaterials due to the varying sizes and shapes of the particles and how these factors affect the biological and mechanical properties. Some papers shows that when absorbed, titanium dioxide can induce genotoxicity, making the compound a possible carcinogen (Trouiller et al.), while other papers cite no evidence of toxicity (Bernard et al.). Overall, there are many possible risks and equally many rewards of utilizing nanoparticles in the composition of sunscreen, and all of these properties must be considered in order to continue progressing forward.
The Beneficial Effects of TiO2 and ZnO Nanoparticles
The skin has three main layers: the epidermis is the outermost and provides a protective barrier around the body, the dermis is the second and contains connective tissues and blood vessels leading into the body, and the hypodermis is the lowest layer made of mostly fat. In commercial sunscreens that incorporate organic materials rather than nanoparticles, there is a higher chance of materials penetrating all the way to the dermis resulting in a reduction in effectiveness and the “inactivation of anti-oxidant species,” which can lead to numerous negative complications such as damage to DNA structure, higher cholesterol, and photoaging (Wakefield et al.). Current research indicates that the use of nanoparticles such as TiO2 and ZnO produces numerous beneficial effects, such as increased UV protection along with a reduction in DNA damage and free radicals (atoms with an odd amount of electrons that are highly reactive and can start a damaging chain reaction inside cells when activated). These nanoparticles also have limited penetration into the epidermis, the upper layer of skin, and do not degrade when exposed to sunlight. A study done by Cross et al. indicates that less than 0.03% of the observed nanoparticles entered the epidermis, suggesting that incorporating nanoparticles in sunscreens heavily reduces the degree of penetration into the epidermis.
Nanoparticles such as TiO2 and ZnO also do not degrade under exposure to sunlight, resulting in less active oxygen species being produced. Active oxygen species are produced by exposure to UVB and UVA radiation; when a person absorbs a high dose of these species, the result is damage to cells and DNA, possibly leading to “photocarcinogenesis and photoaging of the exposed skin,” or the development of cancer and premature aging (Wakefield et al.). With sunscreen comprised of semiconductor oxides such as titania (TiO2) and ZnO, no photodegradation occurs, resulting in a reduction in DNA damage and injury to the skin. Interestingly, an experiment done by Wakefield et al. showed that when dopant ions, used to alter electrical properties and usually composed of manganese or vanadium, are incorporated into nanoparticles, the “production of active oxygen species from sunscreen grade titania can be reduced by over 90%” (Wakefield et al.). These experiments show promising data regarding the beneficial effects of inorganic nanoparticles in sunscreens, yet there still must be more research to make definitive, conclusive statements about the potential side effects.
Potential Side Effects and Health Concerns
Even though the benefits of nanoparticles in sunscreen is potentially revolutionary, there are still numerous side effects to consider. The major potential harm from nanoparticles in sunscreens comes from epidermal application. The potential toxicity concerns of nanosized particles in sunscreens are a result of their size, their ability to evade immunologic defense mechanisms, and most importantly, their ability to induce the formation of free radicals. Nanomaterials by definition have more surface area than larger materials, and because toxicity is determined by surface reactivity, the nanoparticles could exhibit cytotoxicity (Tran et al.). In addition to their size and surface reactivity, nanoparticles may evade the human body’s immune defenses through a variety of mechanisms. In fact, some products containing nanoparticles are intentionally engineered to escape immune surveillance to achieve their desired action.
Serpone et al. described the disastrous effects of micronized TiO2 on DNA. The authors verified TiO2 as an initiator of harmful reactions including DNA strand breaks via free radicals. However, the methods of the study were not described, and thus the results could not be reproduced or analyzed (Serpone et al.). Hidaka et al. studied damage to DNA induced by TiO2 and ZnO after UV exposure. The authors observed an increase in nicks on supercoiled DNA plasmids forming a relaxed and ultimately linear DNA conformation as a result of radicals generated by UV irradiated by TiO2 and ZnO (Hideka et al.). Dufour et al. published a study in 2006 that applied ZnO to Chinese hamster ovarian cells under different 3 conditions: in the dark, under UV light, and pre-irradiated with UV light, followed by treatment with ZnO in the dark. Interestingly, the severity of chromosome mutations in pre-irradiated and simultaneously irradiated cells were nearly identical with regard to toxicity (Dufour et al.). The authors concluded that chromosome aberrations were a result of an enhanced susceptibility of the mammalian cells to ZnO due to UV exposure and thus concluded that ZnO is not toxic to cells or DNA. Despite the studies that suggest nanoparticulate TiO2 and ZnO are potentially toxic to DNA due to the formation of ROS, many researchers believe this should only be viewed as a concern if there were evidence to suggest that nanoparticulate TiO2 and ZnO are capable of penetrating the epidermis. If the nanosized particles in sunscreens applied to the skin penetrate the dermis, there is a concern for systemic absorption of these particles that have potential inflammatory and carcinogenic effects (Ghadially et al.).
The analysis of skin penetration studies must be accepted with caution as skin permeability can vary greatly depending on the compound studied and the species tested. Also, all reviewed studies were conducted on unbroken skin, so further research must be conducted on traumatized or diseased skin to measure the degree of penetration of these nanoparticles (Donaldson et al.). The review of Schafer-Korting et al suggests that although certain skin diseases may affect skin penetration of topical agents, the majority of the literature supports that slightly compromised skin has no greater susceptibility to penetration.
The studies reviewing the safety of nanosized particles in sunscreens must also examine the properties of sunburned skin, as people often reapply sunscreen after they have received substantial sun exposure. Gunther et al determined that the absorption of lotion applied to sunburned skin and intact skin was equal or lower for the sunburned skin. Removal of the epidermis by tape stripping significantly increased penetration of the steroid lotion in both skin types. The authors concluded that inflamed skin produces a thickened epidermis that enhances the barrier function of the skin. Further studies are warranted to determine whether these principles apply to TiO2 and ZnO-based sunscreens applied to damaged skin. Finally, all of the studies reviewed on skin penetration were conducted without control for UV exposure. Therefore, no study has yet simulated the real life scenario for the application of sunscreens. Future studies to determine the safety of ZnO and TiO2 nanosized particles in sunscreens should reproduce a human model for the real-world application of sunscreens including broken skin and accounting for UV exposure (Newman et al.).
While the use of nanoparticles in commercial sunscreens has shown clear benefits, the potential side effects are worrisome and further research must be conducted on this topic. Both TiO2 and ZnO nanoparticles possess reflective properties and are able to scatter UV light, a more effective trait than absorption. However, the main concern with these nanoparticles is their ability to penetrate beyond the skin, leading to continual absorption and genotoxicity. The threat of skin cancer has plagued humanity for centuries, yet nanoparticles could be the key to eliminating this deadly threat. Technology is advancing at an unprecedented rate, and the potential for compounds such as TiO2 and ZnO to revolutionize industries is tremendous. In the near future, nanoparticles will certainly become an integral part of biology, saving the lives of millions.
We’d like to thank our professor, Jagannath Padmanabhan, for giving us the knowledge and resources necessary to write this paper; we’d also like to thank Martin Reyes and Sebastian Aguirre for peer editing our work. Our TAs, Danielle and Chia-ying, also gave us substantial feedback on our drafts and provided us with key points to consider.
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