{"title":"Decoding shape- and type-dependent cellular toxicity of plasmonic nanoparticles in healthy and cancer cells.","authors":"Şevval Çelikten, Jülide Secerli, Onur Erdem, Hakan Erdoğan, Merve Güdül Bacanlı","doi":"10.1080/17435390.2026.2715136","DOIUrl":null,"url":null,"abstract":"<p><p>Plasmonic photothermal therapy (PTT) offers a promising route for selective cancer treatment through laser-activated metallic nanoparticles (NPs). Here, we systematically evaluated how NP geometry, size, and elemental composition govern photothermal toxicity responses in healthy fibroblasts (L929) and lung carcinoma cells (A549) under both laser-free and 808 nm laser-irradiated conditions. Spherical, rod-shaped, and star-shaped gold nanoparticles (AuNP, AuNR, AuNS), together with spherical and prismatic silver nanoparticles (AgNP, AgNPr), were synthesized, characterized, and assessed across multiple biological endpoints. Cellular viability (MTT), reactive oxygen species (ROS) generation, DNA damage (Comet assay), inflammatory cytokine release (TNF-α, IL-6, IL-10), and apoptosis (Annexin V/PI staining and caspase-3/9 activation) were systematically analyzed. Laser activation markedly amplified cancer-selective cytotoxicity, with AuNR and AgNPr exhibiting the strongest photothermal responses while largely sparing healthy cells. AuNR and 20 nm AuNP induced pronounced ROS generation and caspase-dependent apoptosis in A549 cells upon irradiation, whereas AgNPr preferentially promoted DNA damage and inflammatory signaling in cancer cells with minimal effects in L929 cells. Across all nanostructures, laser irradiation selectively intensified genotoxic and inflammatory responses in tumor cells, highlighting a strong dependence on nanoparticle geometry and plasmonic resonance matching. Collectively, these results demonstrate that NP shape and photothermal activation synergistically dictate therapeutic/toxic effects and selectivity. AuNR and AgNPr emerge as leading candidates for precision PTT, combining potent anticancer activity with favorable biocompatibility. This work provides mechanistic insight into structure-activity relationships in plasmonic PTT and informs the rational design of next-generation photothermal nanotherapeutics.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"355-375"},"PeriodicalIF":3.6000,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanotoxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17435390.2026.2715136","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/8/11 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NANOSCIENCE & NANOTECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Plasmonic photothermal therapy (PTT) offers a promising route for selective cancer treatment through laser-activated metallic nanoparticles (NPs). Here, we systematically evaluated how NP geometry, size, and elemental composition govern photothermal toxicity responses in healthy fibroblasts (L929) and lung carcinoma cells (A549) under both laser-free and 808 nm laser-irradiated conditions. Spherical, rod-shaped, and star-shaped gold nanoparticles (AuNP, AuNR, AuNS), together with spherical and prismatic silver nanoparticles (AgNP, AgNPr), were synthesized, characterized, and assessed across multiple biological endpoints. Cellular viability (MTT), reactive oxygen species (ROS) generation, DNA damage (Comet assay), inflammatory cytokine release (TNF-α, IL-6, IL-10), and apoptosis (Annexin V/PI staining and caspase-3/9 activation) were systematically analyzed. Laser activation markedly amplified cancer-selective cytotoxicity, with AuNR and AgNPr exhibiting the strongest photothermal responses while largely sparing healthy cells. AuNR and 20 nm AuNP induced pronounced ROS generation and caspase-dependent apoptosis in A549 cells upon irradiation, whereas AgNPr preferentially promoted DNA damage and inflammatory signaling in cancer cells with minimal effects in L929 cells. Across all nanostructures, laser irradiation selectively intensified genotoxic and inflammatory responses in tumor cells, highlighting a strong dependence on nanoparticle geometry and plasmonic resonance matching. Collectively, these results demonstrate that NP shape and photothermal activation synergistically dictate therapeutic/toxic effects and selectivity. AuNR and AgNPr emerge as leading candidates for precision PTT, combining potent anticancer activity with favorable biocompatibility. This work provides mechanistic insight into structure-activity relationships in plasmonic PTT and informs the rational design of next-generation photothermal nanotherapeutics.
期刊介绍:
Nanotoxicology invites contributions addressing research relating to the potential for human and environmental exposure, hazard and risk associated with the use and development of nano-structured materials. In this context, the term nano-structured materials has a broad definition, including ‘materials with at least one dimension in the nanometer size range’. These nanomaterials range from nanoparticles and nanomedicines, to nano-surfaces of larger materials and composite materials. The range of nanomaterials in use and under development is extremely diverse, so this journal includes a range of materials generated for purposeful delivery into the body (food, medicines, diagnostics and prosthetics), to consumer products (e.g. paints, cosmetics, electronics and clothing), and particles designed for environmental applications (e.g. remediation). It is the nano-size range if these materials which unifies them and defines the scope of Nanotoxicology .
While the term ‘toxicology’ indicates risk, the journal Nanotoxicology also aims to encompass studies that enhance safety during the production, use and disposal of nanomaterials. Well-controlled studies demonstrating a lack of exposure, hazard or risk associated with nanomaterials, or studies aiming to improve biocompatibility are welcomed and encouraged, as such studies will lead to an advancement of nanotechnology. Furthermore, many nanoparticles are developed with the intention to improve human health (e.g. antimicrobial agents), and again, such articles are encouraged. In order to promote quality, Nanotoxicology will prioritise publications that have demonstrated characterisation of the nanomaterials investigated.