Talya Cohen, Chalom Zemmour, Ora T Cohen, Ofra Benny
{"title":"Elongated Particles Show a Preferential Uptake in Invasive Cancer Cells.","authors":"Talya Cohen, Chalom Zemmour, Ora T Cohen, Ofra Benny","doi":"10.3390/nano14231891","DOIUrl":null,"url":null,"abstract":"<p><p>Mechanically driven cellular preference for drug carriers can enhance selectivity in cancer therapy, underscoring the importance of understanding the physical aspects of particle uptake. In this study, it was hypothesized that elongated particles might be preferentially taken up by deformable, aggressive cancer cells compared to normal cells. Two film-stretching methods were tested for 0.8-2.4 μm polystyrene (PS) particles: one based on solubility in organic solvents and the other on heat-induced softening. The heat-induced method produced more homogenous particle batches, with a standard deviation in the particle aspect ratio of 0.42 compared to 0.91 in the solvent-based method. The ability of cells to engulf elongated PS particles versus spherical particles was assessed in two subsets of human melanoma A375 cells. In the more aggressive cancer cell subset (A375+), uptake of elongated PS particles increased by 10% compared to spherical particles. In contrast, the less aggressive subset (A375-) showed a 25% decrease in uptake of elongated particles. This resulted in an uptake ratio between A375+ and A375- that was 1.5 times higher for elongated PS particles than for spherical ones. To further demonstrate relevance to drug delivery, elongated paclitaxel-loaded biodegradable, slow-releasing poly(lactic-co-glycolic) acid (PLGA) particles were synthesized. No significant difference in cytotoxic effect was observed between A375+ and A375- cells treated with spherical drug-loaded particles. However, treatment with ellipsoidal particles led to a significantly enhanced cytotoxic effect in aggressive cells compared to less aggressive cells. These findings present promising directions for tailored cancer drug delivery and demonstrate the importance of particle physical properties in cellular uptake and drug delivery mechanisms.</p>","PeriodicalId":18966,"journal":{"name":"Nanomaterials","volume":"14 23","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanomaterials","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.3390/nano14231891","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Elongated Particles Show a Preferential Uptake in Invasive Cancer Cells.
Mechanically driven cellular preference for drug carriers can enhance selectivity in cancer therapy, underscoring the importance of understanding the physical aspects of particle uptake. In this study, it was hypothesized that elongated particles might be preferentially taken up by deformable, aggressive cancer cells compared to normal cells. Two film-stretching methods were tested for 0.8-2.4 μm polystyrene (PS) particles: one based on solubility in organic solvents and the other on heat-induced softening. The heat-induced method produced more homogenous particle batches, with a standard deviation in the particle aspect ratio of 0.42 compared to 0.91 in the solvent-based method. The ability of cells to engulf elongated PS particles versus spherical particles was assessed in two subsets of human melanoma A375 cells. In the more aggressive cancer cell subset (A375+), uptake of elongated PS particles increased by 10% compared to spherical particles. In contrast, the less aggressive subset (A375-) showed a 25% decrease in uptake of elongated particles. This resulted in an uptake ratio between A375+ and A375- that was 1.5 times higher for elongated PS particles than for spherical ones. To further demonstrate relevance to drug delivery, elongated paclitaxel-loaded biodegradable, slow-releasing poly(lactic-co-glycolic) acid (PLGA) particles were synthesized. No significant difference in cytotoxic effect was observed between A375+ and A375- cells treated with spherical drug-loaded particles. However, treatment with ellipsoidal particles led to a significantly enhanced cytotoxic effect in aggressive cells compared to less aggressive cells. These findings present promising directions for tailored cancer drug delivery and demonstrate the importance of particle physical properties in cellular uptake and drug delivery mechanisms.
期刊介绍:
Nanomaterials (ISSN 2076-4991) is an international and interdisciplinary scholarly open access journal. It publishes reviews, regular research papers, communications, and short notes that are relevant to any field of study that involves nanomaterials, with respect to their science and application. Thus, theoretical and experimental articles will be accepted, along with articles that deal with the synthesis and use of nanomaterials. Articles that synthesize information from multiple fields, and which place discoveries within a broader context, will be preferred. There is no restriction on the length of the papers. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible. Full experimental or methodical details, or both, must be provided for research articles. Computed data or files regarding the full details of the experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material. Nanomaterials is dedicated to a high scientific standard. All manuscripts undergo a rigorous reviewing process and decisions are based on the recommendations of independent reviewers.