水凝胶纳米颗粒，也称为纳米凝胶（NGs），最近被提出作为运输生物相关分子，如抗癌药物和对比剂的替代超分子载体。基于多肽的NGs内部隔室可以根据货物的化学特征适当修改，从而改善其负载和释放性能。对纳米凝胶进入癌细胞和组织的细胞内机制的全面了解，将进一步促进这些纳米载体的潜在诊断和临床应用，允许微调它们的选择性、效力和活性。通过动态光散射（DLS）和纳米颗粒跟踪分析（NTA）分析评估了纳米凝胶的结构特征。使用MTT测定对六种不同乳腺癌细胞系在不同培养时间（24、48和72小时）和肽浓度范围（在6.25×10-4÷5·10-3×wt％之间）下评估Fmoc-FF纳米凝胶的细胞存活率。使用流式细胞术和共聚焦分析分别评估Fmoc-FF纳米凝胶的细胞周期和细胞内摄取机制。Fmoc-FF纳米凝胶具有直径约为130nm和Zeta电位约为-20.0/-25.0 mV的特征，通过空泡(deterioration)进入癌细胞，主要是那些负责白蛋白摄取的细胞。Fmoc-FF纳米凝胶使用的机制的特异性赋予其向过表达蛋白质空泡膜(caveolin1)并有效执行空泡介导的内吞作用的癌细胞系的选择性。

Hydrogel nanoparticles, also known as nanogels (NGs), have been recently proposed as alternative supramolecular vehicles for the delivery of biologically relevant molecules like anticancer drugs and contrast agents. The inner compartment of peptide based NGs can be opportunely modified according to the chemical features of the cargo, thus improving its loading and release. A full understanding of the intracellular mechanism involved in nanogel uptake by cancer cells and tissues would further contribute to the potential diagnostic and clinical applications of these nanocarriers, allowing the fine tuning of their selectivity, potency, and activity. The structural characterization of nanogels were assessed by Dynamic Light Scattering (DLS) and Nanoparticles Tracking Analysis (NTA) analysis. Cells viability of Fmoc-FF nanogels was evaluated by MTT assay on six breast cancer cell lines at different incubation times (24, 48, and 72 h) and peptide concentrations (in the range 6.25 × 10-4 ÷ 5·10-3 × wt%). The cell cycle and mechanisms involved in Fmoc-FF nanogels intracellular uptake were evaluated using flow cytometry and confocal analysis, respectively. Fmoc-FF nanogels, endowed with a diameter of ~130 nm and a zeta potential of ~-20.0/-25.0 mV, enter cancer cells via caveolae, mostly those responsible for albumin uptake. The specificity of the machinery used by Fmoc-FF nanogels confers a selectivity toward cancer cell lines overexpressing the protein caveolin1 and efficiently performing caveolae-mediated endocytosis.