Abstract Nanometric gel particles (CsSH/PEGBCOOH) were successfully synthesized through water in oil (W/O) emulsion by the covalent cross–linking between the primary amines of thiolated chitosan (CsSH) and the dicarboxylic poly(ethylene glycol) (PEG) derivative as cross–linker (PEGBCOOH). Thus, the amidation reaction led to the formation of stable nanosized networks positively or negatively charged by the ionization of either amines or thiol moieties depending on the surrounding pH. This double response, which has not been studied before, was markedly observed and quantified during the characterization of the nanogels, concluding the high impact that could suppose these promising nanoparticles in the biomedical field. Besides, the presence of thiol groups in the nanogels was demonstrated to greatly improve the nanoparticle–mucus interactions, highlighting the potential of this novel strategy in the field of nanotechnology. Finally, nanogels were further labelled with folate ligand as an example of a simple and easy functionalization route via thiol–Michael addition (MA) reaction for future studies of tumour targeting therapies of these nanocarriers. Therefore, the synthesized chitosan–based labelled nanogels presented an adaptable character to the environmental conditions due to their dual pH response and mucoadhesion capacity, making them great candidates as nanocarriers for biomedical applications.

中文翻译：

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双电荷叶酸标记的壳聚糖纳米凝胶具有增强的粘膜粘附能力，用于靶向给药

摘要 通过硫醇化壳聚糖 (CsSH) 的伯胺与二羧酸聚乙二醇 (PEG) 衍生物之间的共价交联，通过油包水 (W/O) 乳液成功合成了纳米凝胶颗粒 (CsSH/PEGBCOOH)。作为交联剂（PEGBCOOH）。因此，酰胺化反应导致稳定的纳米网络的形成，这些网络通过胺或硫醇部分的电离而带正电或负电，这取决于周围的 pH 值。这种以前从未研究过的双重响应在纳米凝胶的表征过程中得到了显着的观察和量化，得出了可能假设这些有前途的纳米粒子在生物医学领域中的巨大影响。此外，纳米凝胶中硫醇基团的存在被证明可以大大改善纳米颗粒 - 粘液的相互作用，突出了这一新战略在纳米技术领域的潜力。最后，纳米凝胶进一步用叶酸配体标记，作为通过硫醇-迈克尔加成 (MA) 反应的简单易行的功能化途径的一个例子，用于这些纳米载体的肿瘤靶向治疗的未来研究。因此，合成的基于壳聚糖的标记纳米凝胶由于其双重 pH 响应和粘膜粘附能力而呈现出对环境条件的适应性，使其成为生物医学应用的纳米载体的理想候选者。纳米凝胶进一步用叶酸配体标记，作为通过硫醇-迈克尔加成 (MA) 反应的简单易行的功能化途径的一个例子，用于这些纳米载体的肿瘤靶向治疗的未来研究。因此，合成的基于壳聚糖的标记纳米凝胶由于其双重 pH 响应和黏膜粘附能力而呈现出对环境条件的适应性，使其成为生物医学应用的纳米载体的理想候选者。纳米凝胶进一步用叶酸配体标记，作为通过硫醇-迈克尔加成 (MA) 反应的简单易行的功能化途径的一个例子，用于这些纳米载体的肿瘤靶向治疗的未来研究。因此，合成的基于壳聚糖的标记纳米凝胶由于其双重 pH 响应和黏膜粘附能力而呈现出对环境条件的适应性，使其成为生物医学应用的纳米载体的理想候选者。