UVR Exposure Research Articles

Non-genetic and genetic predictors of a superficial first basal cell carcinoma.

BackgroundSeveral observational studies have suggested differences in the risk factor profile between patients with superficial basal cell carcinomas (BCCs) and non‐superficial BCCs.ObjectiveTo test the reproducibility of previous study findings and to find new genetic and non‐genetic predictors for patients with a superficial first BCC.MethodsA total of 14.628 participants of northwestern European descent aged 45 years or older from a prospective population‐based cohort study (Rotterdam Study) were linked with the Dutch Pathology Registry (PALGA) of whom 1528 were identified as BCC patients. After exclusion, 948 eligible BCC patients remained for further non‐genetic analyses and 1014 for genetic analyses. We included 11 phenotypic, environmental and tumour‐specific characteristics, and 20 candidate single nucleotide polymorphisms (SNP) as potential predictors for patients with a superficial first BCC. We performed binary logistic multivariable regression analyses.ResultsWe found that patients with a superficial first BCC were significantly younger, almost two times more often female and 12–18 times more likely to have their BCC on the trunk or extremities than patients with a non‐superficial first BCC. One SNP (rs12203592), mapped to IRF4, looked promising (OR 1.83, 95% CI 1.13–2.97, P‐value <0.05), but after adjustment for multiple testing, no significant differences in genetic make‐up between superficial BCC and non‐superficial BCC patients were found.ConclusionWe conclude that patients with a superficial BCC differ from non‐superficial BCC patients with respect to environmental factors (tumour localization as a proxy for UVR exposure) and phenotypic characteristics (age and sex), but we found no difference in genotype. As superficial BCC patients develop their first BCCs at a younger age, they could be at higher lifetime risk for subsequent skin cancers and therefore be an important group for secondary prevention.

Molecular Genomic Profiling of Melanocytic Nevi

The benign melanocytic nevus is the most common tumor in humans and rarely transforms into cutaneous melanoma. Elucidation of the nevus genome is required to better understand the molecular steps of progression to melanoma. We performed whole genome sequencing on a series of 14 benign melanocytic nevi consisting of both congenital and acquired types. All nevi had driver mutations in the MAPK signaling pathway, either BRAF V600E or NRAS Q61R/L. No additional definite driver mutations were identified. Somatic mutations in nevi with higher mutation loads showed a predominance of mutational signatures 7a and 7b, consistent with UVR exposure, whereas nevi with lower mutation loads (including all three congenital nevi) had a predominance of the ubiquitous signatures 1 and 5. Two nevi had mutations in promoter regions predicted to bind E26 transformation-specific family transcription factors, as well as subclonal mutations in the TERT promoter. This paper presents whole genome data from melanocytic nevi. We confirm that UVR is involved in the etiology of a subset of nevi. This study also establishes that TERT promoter mutations are present in morphologically benign skin nevi in subclonal populations, which has implications regarding the interpretation of this emerging biomarker in sensitive assays.

Adult UVR exposure changes with life stage - a 14-year follow-up study using personal electronic UVR dosimeters.

Over a period spanning 14 years (1999-2001, 2006 and 2012), 31 volunteers participated in sun behaviour studies with the same protocol wearing a personal, electronic wrist-borne UVR dosimeter and completed sun exposure diaries resulting in a total of 15 946 measurements days (126 days per person per year). The participants individually maintained their UVR dose level and behaviour over the years. No statistically significant differences were seen from year to year in the "estimated annual UVR dose", the "mean UVR dose per day", the "mean percentage of ambient UVR", "days sunbathing to get a tan", "days with intermittent exposure" or in "sunburn episodes". The 20 participants still active in the labour market used sunscreen on more days in 2012 than in 1999 (p = 0.019) and with a significantly higher SPF (sun protecting factor (p < 0.001)) resulting in significantly fewer days with risk behaviour without sunscreen applied in 2012 than in 2006 (p < 0.001) and 1999 (p < 0.003). This was in contrast to the 11 participants who retired during the study period. The retired group received a non-significant 45% higher UV dose in 2012 than in 1999 (p = 0.054). In an additional study, nine 30-year-old indoor workers (high school students in the 1999 study) had changed their sun exposure pattern and had fewer days sunbathing (p = 0.008) and fewer risk behaviour days without sunscreen applied in 2012 than in 1999 (p = 0.002). Conclusion: The participants still active in the labour market maintained their sun exposure behaviour over a 14-year period. The retirees had a higher UVR dose and riskier exposure behaviour after retirement, while the high school students had changed to less risky sun behaviour on becoming indoor workers.

Different genetic mechanisms mediate spontaneous versus UVR-induced malignant melanoma.

Genetic variation conferring resistance and susceptibility to carcinogen-induced tumorigenesis is frequently studied in mice. We have now turned this idea to melanoma using the collaborative cross (CC), a resource of mouse strains designed to discover genes for complex diseases. We studied melanoma-prone transgenic progeny across seventy CC genetic backgrounds. We mapped a strong quantitative trait locus for rapid onset spontaneous melanoma onset to Prkdc, a gene involved in detection and repair of DNA damage. In contrast, rapid onset UVR-induced melanoma was linked to the ribosomal subunit gene Rrp15. Ribosome biogenesis was upregulated in skin shortly after UVR exposure. Mechanistically, variation in the 'usual suspects' by which UVR may exacerbate melanoma, defective DNA repair, melanocyte proliferation, or inflammatory cell infiltration, did not explain melanoma susceptibility or resistance across the CC. Instead, events occurring soon after exposure, such as dysregulation of ribosome function, which alters many aspects of cellular metabolism, may be important.

Exposure to Solar UVR Suppresses Cell-Mediated Immunization Responses in Humans: The Australian Ultraviolet Radiation and Immunity Study

Animal and human studies show that exposure to solar-simulated UVR is immunomodulatory. Human studies that used natural sun exposure and controlled for confounding are rare. We immunized 217 healthy adults (age range= 18-40 years) with a T-cell-dependent antigen, keyhole limpet hemocyanin, and measured personal clothing-adjusted UVR exposure (for 5 days before and after immunization), lifetime cumulative UVR exposure, serum 25-hydroxyvitamin D concentration at immunization, and potential confounding factors. We tested cellular and humoral immune responses in relation to UVR exposure. The delayed-type hypersensitivity response to keyhole limpet hemocyanin recall challenge was lower in individuals with higher personal clothing-adjusted UVR exposure on the day before immunization (P= 0.015) and during intervals spanning the day before to 2-3 days after immunization. There was an incremental increase in T helper type 17 cells (as a proportion of CD4+ T cells) from preimmunization to postimmunization in the high, compared with the low, personal clothing-adjusted UVR exposure group (0.31% vs. -0.39%, P= 0.004). Keyhole limpet hemocyanin-specific antibody titers were not associated with acute or cumulative UVR exposure or serum 25-hydroxyvitamin D levels. Higher UVR exposure at antigen sensitization was associated with a reduced delayed-type hypersensitivity response and altered T helper type 17 kinetics. This has implications for the effectiveness of vaccinations and susceptibility to infections that rely on cell-mediated immune responses.

Single center evidence for the treatment of basal cell carcinoma of the head and neck.

Aim: Basal Cell Carcinoma (BCC) alone accounts for 80% of cases of non-melanoma skin cancer (NMSC), which characteristically develops on sun-exposed skin. Indeed the most common site of BCC is the head and neck region (80%). The purpose of this study to review the experience of our center with BCC in the head and neck region to report the sites of occurrence and treatment. Materials and method: We retrospectively reviewed 77 patients with BCC of the head and neck, who revived surgical treatment within our plastic surgery division. Basic demographic data, cancer site and size, surgical treatment and histological data were collected. The mean follow-up period was 12 months. Results: The study population included 37 males and 40 females, with a mean age of 74.12 years. The nasal unit was the main site of BCC (31.82%), followed by the periorbital (13.64%) and cervical (12.5%) units. Primary closure was the main surgical procedure performed (72.5%), followed by local flap (26.1%) and full-thickness skin grafts (1.4%). The safety resection margin ranged from 4.5 to 9 mm, with a 98.7% complete removal rate. Neither recurrence nor any newly-developed lesions were reported during follow-up in any patient. Discussion: Our work reflects the shift in the incidence of BCC, which now seems to be more frequent in females. Furthermore, our data strengthens the association between UVR exposure and BCC, confirms its predilection to occur on the nasal unit and validates surgical excision as the gold standard treatment for skin cancer. (www.actabiomedica.it)

Development of Multiple-Lesion Basal Cell Carcinoma of the Skin: A Comprehensive Review.

An interesting clinical feature of basal cell carcinoma (BCC) of the skin is a marked variation in tumor number, sites, and accrual. Some individuals develop only a single BCC lesion with no impact on health status, while a significant proportion is affected repeatedly with new primary tumors at various body sites. Approximately 29% of patients with a first BCC will develop at least 1 more lesion during their lifetime. The candidate predictors for multiple BCC development include younger age and a superficial BCC subtype at the time of the first diagnosis, red hair phenotype, initial or frequent tumor location on the trunk or on the upper limbs, and male gender. The pathogenesis of multiple BCC development does not seem to be related to greater UVR exposure. Individual genetic susceptibility may have a greater impact than extrinsic factors. In clinical practice, it is meaningful to estimate the probability of new BCC development in patients who have an initial lesion. A reliable prediction model for individualized risk stratification remains a subject of continued research; however, a focus on the risk factor profile is beneficial for clinical screening and may help clinicians to determine the individuals who should be followed up more closely.

T Regulatory Cell Subpopulations Associated with Recent Ultraviolet Radiation Exposure in a Skin Cancer Screening Cohort.

UV radiation (UVR) causing DNA damage is a well-documented risk factor for nonmelanoma skin cancer. Although poorly understood, UVR may also indirectly contribute to carcinogenesis by promoting immune evasion. To our knowledge, we report the first epidemiological study designed to investigate the association between quantitative measures of UVR, obtained using a spectrophotometer, and circulating T regulatory (Treg) cells. In addition to total Treg cells, the proportion of functionally distinct Treg cell subsets defined by CD45RA and CD27 phenotypic markers, graded expression of FOXP3 and CD25, and those expressing cutaneous lymphocyte-associated Ag and the chemokine receptor CCR4 were enumerated in 350 individuals undergoing routine skin cancer screening exams and determined not to have prevalent skin cancer. No associations were identified for UVR exposure or the overall proportion of circulating Treg cells; however, Treg cell subpopulations with an activation-associated phenotype, CD45RA-/CD27-, and those expressing cutaneous homing receptors were significantly positively associated with UVR. These subpopulations of Treg cells also differed by age, sex, and race. After stratification by natural skin tone, and adjusting for age and sex, we found that spectrophotometer-based measures of UVR exposure, but not self-reported measures of past sun exposure, were positively correlated with the highest levels of these Treg cell subpopulations, particularly among lighter-skinned individuals. Findings from this large epidemiologic study highlight the diversity of human Treg cell subpopulations associated with UVR, thus raising questions about the specific coordinated expression of CD45RA, CD27, CCR4, and cutaneous lymphocyte-associated Ag on Treg cells and the possibility that UVR contributes to nonmelanoma skin cancer carcinogenesis through Treg cell-mediated immune evasion.

Ultraviolet radiation-induced immunosuppression and its relevance for skin carcinogenesis.

The realisation that UV radiation (UVR) exposure could induce a suppressed immune environment for the initiation of carcinogenesis in the skin was first described more than 40 years ago. Van der Leun and his colleagues contributed to this area in the 1980s and 90s by experiments in mice involving UV wavelength and dose-dependency in the formation of such tumours, in addition to illustrating both the local and systemic effect of the UVR on the immune system. Since these early days, many aspects of the complex pathways of UV-induced immunosuppression have been studied and are outlined in this review. Although most experimental work has involved mice, it is clear that UVR also causes reduced immune responses in humans. Evidence showing the importance of the immune system in determining the risk of human skin cancers is explained, and details of how UVR exposure can down-regulate immunity in the formation and progression of such tumours reviewed. With increasing knowledge of these links and the mechanisms of UVR-induced immunosuppression, novel approaches to enhance immunity to skin tumour antigens in humans are becoming apparent which, hopefully, will reduce the burden of UVR-induced skin cancers in the future.

Association of Increased Sun Exposure Over the Life-course with a Reduced Risk of Juvenile Idiopathic Arthritis.

Cutaneous sun exposure is an important determinant of circulating vitamin D. Both sun exposure and vitamin D have been inversely associated with risk of autoimmune disease. In juvenile idiopathic arthritis (JIA), low circulating vitamin D appears common, but disease-related behavioral changes may have influenced sun exposure. We therefore aimed to determine whether predisease sun exposure is associated with JIA. Using validated questionnaires, we retrospectively measured sun exposure for 202 Caucasian JIA case-control pairs born in Victoria Australia, matched for birth year and time of recruitment. Measures included maternal sun exposure at 12weeks of pregnancy and child sun exposure across the life-course prediagnosis. We converted exposure to UVR dose and looked for case-control differences using logistic regression, adjusting for potential confounders. Higher cumulative prediagnosis UVR exposure was associated with reduced risk of JIA, with a clear dose-response relationship (trend P=0.04). UVR exposure at 12weeks of pregnancy was similarly inversely associated with JIA (trend P=0.011). Associations were robust to sensitivity analyses for prediagnosis behavioral changes, disease duration and knowledge of the hypothesis. Our data indicate that lower UVR exposure may increase JIA risk. This may be through decreased circulating vitamin D, but prospective studies are required to confirm this.

Brahma deficiency in keratinocytes promotes UV carcinogenesis by accelerating the escape from cell cycle arrest and the formation of DNA photolesions

BackgroundUltraviolet radiation (UVR) is the principal cause of keratinocyte skin cancers. Previous work found that levels of the chromatin remodelling protein, Brahma (Brm), are diminished during the progression from actinic keratoses to cutaneous squamous cell carcinomas in humans, and its loss in UV-irradiated mouse skin causes epidermal hyperplasia and increased tumour incidence. MethodsThe skins of mice and mouse and human keratinocytes deficient in Brm were exposed to UVR and evaluated for cell cycle progression and DNA damage response. ObjectiveTo identify the mechanisms by which loss of Brm contributes to UVR-induced skin carcinogenesis. ResultsIn both mouse keratinocytes and HaCaT cells, Brm deficiency led to an increased cell population growth following UVR exposure compared to cells with normal levels of Brm. Cell cycle analysis using a novel assay showed that Brm-deficient keratinocytes entered cell cycle arrest normally, but escaped from cell cycle arrest faster, enabling them to begin proliferating earlier. In mouse keratinocytes, Brm primarily affected accumulation in G0/G1-phase, whereas in HaCaT cells, which lack normal p53, accumulation in G2/M-phase was affected. Brm-deficient keratinocytes in mouse skin and human cell cultures also had higher levels of UVR-induced cyclobutane pyrimidine dimer photolesions. These effects occurred without any compensatory increase in DNA repair or cell death to remove photolesions or the cells that harbor them from the keratinocyte population. ConclusionThe loss of Brm in keratinocytes exposed to UVR enables them to resume proliferation while harboring DNA photolesions, leading to an increased fixation of mutations and, consequently, increased carcinogenesis.

Effects of ultraviolet radiation and nutrient level on the physiological response and organic matter release of the scleractinian coral Pocillopora damicornis following thermal stress.

Understanding which factors enhance or mitigate the impact of high temperatures on corals is crucial to predict the severity of coral bleaching worldwide. On the one hand, global warming is usually associated with high ultraviolet radiation levels (UVR), and surface water nutrient depletion due to stratification. On the other hand, eutrophication of coastal reefs increases levels of inorganic nutrients and decreases UVR, so that the effect of different combinations of these stressors on corals is unknown. In this study, we assessed the individual and crossed effects of high temperature, UVR and nutrient level on the key performance variables of the reef building coral Pocillopora damicornis. We found that seawater warming was the major stressor, which induced bleaching and impaired coral photosynthesis and calcification in all nutrient and UVR conditions. The strength of this effect however, was nutrient dependent. Corals maintained in nutrient-depleted conditions experienced the highest decrease in net photosynthesis under thermal stress, while nutrient enrichment (3 μM NO3- and 1 μM PO4+) slightly limited the negative impact of temperature through enhanced protein content, photosynthesis and respiration rates. UVR exposure had only an effect on total nitrogen release rates, which significantly decreased under normal growth conditions and tended to decrease also under thermal stress. This result suggests that increased level of UVR will lead to significant changes in the nutrient biogeochemistry of surface reef waters. Overall, our results show that environmental factors have different and interactive effects on each of the coral’s physiological parameters, requiring multifactorial approaches to predict the future of coral reefs.

Growth and Fv/Fm in embryos of Hizikia fusiformis (Harvey) Okamura (Sargassaceae, Phaeophyta) cultured under different temperature and irradiance conditions

Understanding the embryo physiology of Hizikia fusiformis (Harvey) Okamura will promote the development of artificial seedlings. In this study, H. fusiformis embryos were cultured under different environmental conditions, including different temperatures (15°C, 20°C, and 25°C), sunlight intensities (100%, 50%, and 25% of full solar radiation) and types of UVR (UV-A and UV-B). Then, we determined the lengths, maximal quantum yields ( Fv/Fm ), and survival rates of the embryos. The results showed that the embryos had the highest lengths, Fv/Fm values and survival percentages when cultured under a temperature of 20°C and 25% sunlight intensity. The full level of solar radiation severely reduced the growth and survival ratios of the embryos. Hizikia embryos recovered within 2 h from the damage caused by short-term (30 min) high radiation (about 70% of full solar radiation) and UVR exposure. However, the viabilities of the embryos were significantly decreased after 4 h exposure to UVR. According to these results, we propose that culture conditions with indoor natural light and room temperature would be favorable for the growth, development and physiology of Hizikia embryos.

Corrigendum to "PLGA nanoformulation of sparfloxacin enhanced antibacterial activity with photoprotective potential under ambient UV-R exposure" [Int. J. Pharm. 541 (2018) 173-187

Corrigendum to "PLGA nanoformulation of sparfloxacin enhanced antibacterial activity with photoprotective potential under ambient UV-R exposure" [Int. J. Pharm. 541 (2018) 173-187

The mycosporine-like amino acids porphyra-334 and shinorine are antioxidants and direct antagonists of Keap1-Nrf2 binding

Mycosporine-like amino acids (MAAs) are UVR-absorbing metabolites typically produced by cyanobacteria and marine algae, but their properties are not limited to direct sun screening protection. Herein, we examine the antioxidant activities of porphyra-334 and shinorine and demonstrate that these MAAs are prospective activators of the cytoprotective Keap1-Nrf2 pathway. The ability of porphyra-334 and shinorine to bind with Keap1 was determined using fluorescence polarization (FP) and thermal shift assays to detect Keap1 receptor antagonism. Concomitantly, the ability of porphyra-334 and shinorine to dissociate Nrf2 from Keap1 was confirmed also by measurement of increased mRNA expression of Nrf2 targeted genes encoding oxidative stress defense proteins in primary skin fibroblasts prior and post UVR exposure. Surprisingly, enhanced transcriptional regulation was only promoted by MAAs in cells after exposure to UVR-induced oxidative stress. Furthermore, the in-vitro antioxidant activities of porphyra-334 and shinorine determined by the DPPH free-radical quenching assay were low in comparison to ascorbic acid. However, their antioxidant capacity determined by the ORAC assay to quench free radicals via hydrogen atom transfer is substantial. Hence, the dual nature of MAAs to provide antioxidant protection may offer a prospective chemotherapeutic strategy to prevent or retard the progression of multiple degenerative disorders of ageing.

Synthesis and characterization of rare earth activated barium zirconate ceramic

This paper reports synthesis of rare earth doped BZO perovskite ceramic by facile solid state reaction synthesis route. The phosphor confirms its nanocrystalline structure with high order purity and homogeneity. Characterized by XRD, SEM, EDX, FTIR and TL, a complete investigation of its structural, morphological and thermoluminescent properties is done. The kinetic parameters estimated using peak shape method confirms the second order kinetics of synthesized ceramic powder. With the emerging global concern regarding UVR exposure protection, the BZO perovskite ceramic are emerging as dynamic alternatives for TL mapping.

Vegetation transitions drive the autotrophy–heterotrophy balance in Arctic lakes

Abstract“Arctic greening” will alter vegetation quantity and quality in northern watersheds, with possible consequences for lake metabolic balance. We used paleolimnology from six Arctic lakes in Greenland, Norway, and Alaska to develop a conceptual model describing how climate‐driven shifts in terrestrial vegetation (spanning herb to boreal forest) influence lake autotrophic biomass (as chlorophyll and carotenoid pigments). Major autotrophic transitions occurred, including (1) optimal production of siliceous algae and cyanobacteria/chlorophytes at intermediate vegetation cover (dwarf shrub and Betula; dissolved organic carbon (DOC) range of 2–4 mg L−1), below and above which UVR exposure (DOC; &lt; 2 mgL−1) and light extinction (DOC; &gt; 4 mgL−1), respectively limit algal biomass, (2) an increase in potentially mixotrophic cryptophytes with higher forest cover and allochthonous carbon supply. Vegetation cover appears to influence lake autotrophs by changing influx of (colored) dissolved organic matter which has multiple interacting roles—as a photoprotectant—in light attenuation and in macronutrient (carbon, nitrogen) supply.

Adapting a Skin Cancer Prevention Intervention for Multiethnic Adolescents.

We tested the effectiveness of a school-based skin cancer prevention intervention entitled "SunSafe in the Middle School Years" adapted for multiethnic high school students. In Hawai'i, 208 10th graders (51.6% Asian, 30.4% Native Hawaiian/Pacific Islander, 8.4% white, 3.5% Hispanic, 2.7% black) participated. Changes in sun protection knowledge, attitudes, and self-reported behaviors were measured using a standardized 18-item survey. The Systematic Observation of Sun Protection Factors (SOSPF) instrument assessed aggregate sun protection behaviors. At posttest, improvements were found in 13 of 18 survey items (p < .05), and retained in 10 items at 12-months following baseline assessments; sun-protection attitudes and intended tanning behavior did not show improvement. Six observers using SOSPF reliably measured students' sun protection behaviors at school including use of hats, sunglasses, long sleeves, lower body coverage, and shade (ICC > .77). We uncovered a lack of knowledge about UVR exposure, tanning, and lifetime skin cancer risk among multiethnic high school students. We found that students' tanning attitudes may be influenced by self-perceptions regarding their own complexion, but were willing to modify their sun protection behaviors once informed about skin cancer risk.

Family History of Melanoma and Lifetime Patterns of Daytime Hours Spent Outdoors in Melanoma-prone Families

Abstract Longer daytime hours spent outdoors reflect higher ultraviolet radiation exposure, which is a modifiable risk factor of melanoma. Among individuals of melanoma-prone families, we sought to describe lifetime patterns for hours spent outdoors, and to investigate whether having an affected family member with melanoma from an older generation was associated with patterning. Methods: Information on hours spent outdoors on weekdays, weekends, and holidays beginning at age 10 was obtained from individuals from melanoma-prone families. We determined time-weighted average hours outdoors for warmer months, colder months, and the entire year. K-means for longitudinal data was used to identify lifetime patterns. We created a variable to indicate whether there was an existing melanoma in a prior generation of an individual's family. Multinomial logistic regression models were used to examine the association between family history of melanoma and lifetime patterns of daytime hours spent outdoors, adjusting for covariates. Results: We analyzed 2540 individuals from 669 families ascertained across 15 countries, and four lifetime patterns were identified. Three patterns began with moderate hours that (B) decreased slowly (n = 1014); (C) decreased sharply until age 20 and then remained low (n = 572); or (D) increased at age 20 and remained high (n = 173). One pattern, (A) began with few hours that decreased at age 20 then remained very low (n = 781). Compared to individuals with the high (D) pattern, individuals with an existing melanoma in a prior family generation were more likely to have the low (A) pattern (OR = 1.92, 95% CI: 1.34–2.76), the moderate and slowly decreasing (B) pattern (OR = 1.72, 95% CI: 1.15–2.57), or the sharply decreasing (C) pattern (OR = 2.01, 95% CI: 1.40–2.87). Similar associations were observed separately in warmer and colder months. Examining lifetime patterns of hours spent outdoors during holidays, we noticed a stronger relationship with family history of melanoma in warmer months than in colder months. Conclusions: As expected, the diagnosis of a melanoma in a prior generation may impact family members' awareness of UVR exposure leading to reduced daytime hours spent outdoors.

PLGA nanoformulation of sparfloxacin enhanced antibacterial activity with photoprotective potential under ambient UV-R exposure

Sparfloxacin (SPFX) is a broad spectrum antibiotic which inhibits bacterial DNA gyrase enzyme activity. However, photodegradation in the presence of UVA limits its antibacterial activity and induces phototoxicity. Thus, to encounter this problem, we have developed poly d,l-lactic-co-glycolic acid (PLGA) loaded SPFX nanoparticles. Here, we have performed a comparative antibacterial activity of SPFX and its nanoparticles (NPs) through molecular docking and plate sensitivity assay. Under environmental UVA exposure, photoexcited SPFX significantly generates ROS, DNA damage and mitochondrial mediated cell death in comparison to PLGA-SPFX-NPs (nano SPFX) in human skin cell line (HaCaT). In presence of UVA, bulk SPFX induced cell cycle arrest with appearance of sub-G1 peak showing apoptosis while nano SPFX did not show any change. SPFX triggered apoptosis via alteration in membrane integrity of mitochondria and lysosome in comparison to PLGA-SPFX-NPs. Involvement of mitochondrial mediated cell death was confirmed by down-regulation of anti-apoptotic Bcl-2 and procaspase-3 and upregulation of pro-apoptotic Bax, cytochrome-c and caspase-3 proteins expression. Specific caspase inhibitor, Z-VAD-FMK showed involvement of caspase cascade pathway in apoptosis. Our finding suggests that controlled release of SPFX from PLGA-SPFX-NPs can reduce its side effects and enhance its antibacterial activity. Thus, nanotization of fluoroquinolones will be a significant step to reduce the problem of resistance and phototoxicity of this group.