Center for Nanotechnology Innovation@NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, 56127 Pisa, Italy.
NEST, Scuola Normale Superiore, Piazza San Silvestro 12, 56127 Pisa, Italy.
Molecules. 2020 May 10;25(9):2252. doi: 10.3390/molecules25092252.
Nanoparticles are widely used as theranostic agents for the treatment of various pathologies, including cancer. Among all, dendrimers-based nanoparticles represent a valid approach for drugs delivery, thanks to their controllable size and surface properties. Indeed, dendrimers can be easily loaded with different payloads and functionalized with targeting agents. Moreover, they can be used in combination with other materials such as metal nanoparticles for combinatorial therapies. Here, we present the formulation of an innovative nanostructured hybrid system composed by a metallic core and a dendrimers-based coating that is able to deliver doxorubicin specifically to cancer cells through a targeting agent. Its dual nature allows us to transport nanoparticles to our site of interest through the magnetic field and specifically increase internalization by exploiting the T7 targeting peptide. Our system can release the drug in a controlled pH-dependent way, causing more than 50% of cell death in a pancreatic cancer cell line. Finally, we show how the system was internalized inside cancer cells, highlighting a peculiar disassembly of the nanostructure at the cell surface. Indeed, only the dendrimeric portion is internalized, while the metal core remains outside. Thanks to these features, our nanosystem can be exploited for a multistage magnetic vector.
纳米粒子被广泛用作治疗各种病理的治疗和诊断试剂，包括癌症。在所有的纳米粒子中，基于树枝状大分子的纳米粒子代表了一种有效的药物传递方法，因为它们的尺寸和表面特性可控。事实上，树枝状大分子可以很容易地负载不同的有效载荷，并通过靶向剂进行功能化。此外，它们可以与其他材料如金属纳米粒子结合用于联合治疗。在这里，我们提出了一种由金属核和基于树枝状大分子的涂层组成的创新纳米结构杂化系统的配方，该系统能够通过靶向剂将阿霉素特异性递送到癌细胞中。其双重性质使我们能够通过磁场将纳米粒子输送到我们感兴趣的部位，并通过利用 T7 靶向肽特异性增加内化。我们的系统可以在受控的 pH 依赖性方式下释放药物，导致胰腺癌细胞系中超过 50%的细胞死亡。最后，我们展示了该系统如何被内化到癌细胞中，突出显示了纳米结构在细胞表面的特殊解体。事实上，只有树枝状大分子部分被内化，而金属核仍然留在外面。由于这些特性，我们的纳米系统可以用于多阶段磁性载体。
