Nanomedicine formulations such as biodegradable nanoparticles (nps) and liposomes offer several advantages over traditional routes of administration: due to their small size, nanocarriers are able to selectively accumulate inside tumours or inflammatory tissues, resulting in improved drug efficacy and reduced side effects. To further augment targeting ability of nanoparticles towards tumour cells, specific ligands or antibodies that selectively recognise biomarkers over-expressed on cancer cells, can be attached to the surface either by chemical bond or by hydrophilic/hydrophobic interactions. In the present work, Herceptin (HER), a monoclonal antibody (mAb) able to selectively recognise HER-2 over-expressing tumour cells (such as breast and ovarian cancer cells), was absorbed on the surface of nanoparticles through hydrophilic/hydrophobic interactions. Nps were prepared by a modified single emulsion solvent evaporation method with five different polymers: three commercial polyesters (poly(ε-caprolactone) (PCL), poly (D,L-lactide) (PLA) and poly (D,L-lactide-co-.glycolide) (PLGA)) and two novel biodegradable polyesterurethanes (PURs) based on Poly(ε-caprolactone) blocks, synthesised with different chain extenders (1,4-cyclohexane dimethanol (CDM) and N-Boc-serinol). Polyurethanes were introduced as matrix-forming materials for nanoparticles due to their high chemical versatility, which allows tailoring of the materials final properties by properly selecting the reagents. All nps exhibited a small size and negative surface charge, suitable for surface functionalisation with mAb through hydrophilic/hydrophobic interactions. The extent of cellular internalisation was tested on two different cell lines: MCF-7 and SK-BR-3 breast cancer cells showing a normal and a high expression of the HER-2 receptor, respectively. Paclitaxel, a model anti-neoplastic drug, was encapsulated inside all nps, and release profiles and cytotoxicity on SK-BR-3 cells were also assessed. Interestingly, PUR nps were superior to commercial polyester-based nps in terms of higher cellular internalisation and cytotoxic activity on the tested cell lines. Results obtained warrants further investigation on the application of these PUR nps for controlled drug delivery and targeting.

译文

纳米药物制剂 (例如可生物降解的纳米颗粒 (nps) 和脂质体) 比传统的给药途径具有多个优势: 由于其体积小,纳米载体能够选择性地在肿瘤或炎症组织内积聚,从而提高药物功效并减少副作用。为了进一步增强纳米颗粒对肿瘤细胞的靶向能力,可以通过化学键或通过亲水/疏水相互作用将选择性识别在癌细胞上过度表达的生物标志物的特异性配体或抗体附着到表面。在目前的工作中,赫赛汀 (HER) 是一种能够选择性识别HER-2过表达肿瘤细胞 (如乳腺癌和卵巢癌细胞) 的单克隆抗体 (mAb),通过亲水/疏水相互作用被吸收在纳米颗粒的表面上。用五种不同的聚合物通过改进的单乳液溶剂蒸发法制备了Nps: 三种商业聚酯 (聚 (ε-己内酯) (PCL),聚 (D,L-丙交酯) (PLA) 和聚 (D,L-丙交酯-co-乙交酯 (PLGA)) 和两种基于聚 (ε-己内酯) 嵌段的新型可生物降解的聚酯氨基甲酸酯 (PURs),用不同的扩链剂 (1,4-环己烷二甲醇 (CDM) 和N-Boc-丝氨酸) 合成。由于聚氨酯具有很高的化学通用性,因此被引入作为纳米颗粒的基质形成材料,这可以通过适当选择试剂来调整材料的最终性能。所有np均显示出小尺寸和负表面电荷,适合通过亲水/疏水相互作用与mAb进行表面官能化。在两种不同的细胞系上测试了细胞内在化的程度: 分别显示正常和高表达HER-2受体的MCF-7和SK-BR-3乳腺癌细胞。将紫杉醇 (一种模型抗肿瘤药物) 封装在所有np中,并评估其释放特性和对SK-BR-3细胞的细胞毒性。有趣的是,PUR nps在测试细胞系上具有更高的细胞内在化和细胞毒性活性方面优于商业基于聚酯的nps。获得的结果值得进一步研究这些PUR np在受控药物输送和靶向方面的应用。

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