Uniform block copolymer nanofibers for the delivery of paclitaxel in 2D and 3D glioblastoma tumor models.

Cancer treatment has transformed in recent years, with the introduction of immunotherapy providing substantial improvements in prognoses for certain cancers. However, traditional small molecule chemotherapeutics remain the major frontline of defence, and improving their delivery to solid tumors is of utmost importance for improving potency and reducing side effects. Here, length-controlled one-dimensional seed nanofibers (ca. 25 nm, DL = 1.05) were generated from poly(fluorenetrimethylenecarbonate)-block-poly(dimethylaminoethylmethacrylate) via living crystallization-driven self-assembly. Paclitaxel, with an encapsulation content ranging from 1 to 100 wt%, was loaded onto the preformed nanoparticles by solvent addition and evaporation. Drug loading was quantified by dynamic light scattering and transmission electron microscopy. Drug-loaded vectors were then incubated with U87 MG glioblastoma cells in a 2D cell assay for up to 72 h, and their anticancer properties were determined. It was observed that seed nanofibers loaded with 20 wt% paclitaxel were the most advantageous combination (IC50 = 0.48 µg mL-1), while pure seed nanofibers with no loaded drug displayed much lower cytotoxicity (IC50 = 11.52 µg mL-1). The IC50 of the loaded seed nanofibers rivaled that of the commercially approved Abraxane® (IC50 = 0.46 µg mL-1). 3D tumor spheroids were then cultured and subjected to the same stresses. Live/dead cell staining revealed that once more, seed nanofibers with 20 wt% paclitaxel, Abraxane®, and paclitaxel all exhibited similar levels of potency (55% viability), whereas control samples exhibited much higher cell viability (70%) after 3 days. These results demonstrate that nanofibers contain great potential as biocompatible drug delivery vehicles for cancer treatment as they exert a similar anticancer effect to the commercially available Abraxane®.

[Tobacco dependency and adolescents: a good time to give up smoking? Relation to social and family factors]. / Tabaquismo y adolescentes: 'buen momento para dejar de fumar? Relación con factores sociofamiliares.

OBJECTIVES: To find the prevalence and dependency of adolescents on tobacco, its relation with family and social factors and the motivation for giving up smoking. DESIGN: Cross-sectional, descriptive study using questionnaires. SETTING: Secondary school, Jaén, Spain. PARTICIPANTS AND MEASUREMENTS: A total of 232 students: the questionnaire included questions on age, sex, tobacco consumption, smoking habits of family and friends, and family structure. The following tests were given: the Apgar family (AFT), Fagerström (FT), and Richmond (RT) tests. RESULTS: Mean age 14.1 years old (95% CI, 13.9-14.3; range, 5 years); 57% boys. A 22% (17.1%-24.5%) were smokers, most of whom were boys (65.2%-86.7%; P<.001, *2) and were older than non-smokers (0.7-1.5; P<.001, Student's t). Mean consumption was 9.2 cigarettes a day (7.4-11.0) over 32 months (14.6-49.5). Friends who smoked were more frequent among adolescents who smoked (80.9%-99%) than among non-smokers (57.3%-70.6%; P<.001, *2). Smoking every day increased consumption by 6 cigarettes a day (3.6-9.2; P<.001, Student's t). In 71% (65.3%-76.6%) of families, there were smokers, principally the parents (63.3%-74.6%), who, in 85% (74.2%-95.8%) of cases, disapproved of their son/daughter smoking. Family dysfunction was more frequent in smokers (30% mild [16.1%-43.9%] and 17% severe [5.4%-28.6%]; P<.001, *2). The FT was positive for 12% (2%-22%) and was associated with the consumption of cigarettes per day (r=0.78; P<.05, Pearson). The RT was positive for 22% (15.1%-28.9%): 70% in the contemplation stage (55.6%-84.3%); 17% in preparation (5.4%-28.6%); 13% in action (3%-23%). CONCLUSIONS: The consumption of tobacco among adolescents is related to family function and having friends who smoke. The low dependency and the motivation to change make this stage of life a good moment to concentrate on anti-smoking counselling.