Chillà Anastasia, Margheri Francesca, Biagioni Alessio, Del Rosso Tommaso, Fibbi Gabriella, Del Rosso Mario, Laurenzana Anna
Department of Experimental and Clinical Biomedical Sciences School of Health Sciences, University of Florence-Viale G.B. Morgagni, 50-50134 Florence, Italy.
Department of Physics, Pontifical Catholic University of Rio de Janeiro, 22451-900 Rio de Janeiro-RJ, Brazil.
Cancers (Basel). 2020 Jul 2;12(7):1771. doi: 10.3390/cancers12071771.
Targeted and immune therapies have unquestionably improved the prognosis of melanoma patients. However the treatment of this neoplasm still requires approaches with a higher therapeutic index, in order to reduce shortcomings related to toxic effects and aspecific targeting. This means developing therapeutic tools derived with high affinity molecules for tumor components differentially expressed in melanoma cells with respect to their normal counterpart. Nanomedicine has sought to address this problem owing to the high modulability of nanoparticles. This approach exploits not only the enhanced permeability and retention effect typical of the tumor microenvironment (passive targeting), but also the use of specific "molecular antennas" that recognize some tumor-overexpressed molecules (active targeting). This line of research has given rise to the so-called "smart nanoparticles," some of which have already passed the preclinical phase and are under clinical trials in melanoma patients. To further improve nanoparticles partition within tumors, for some years now a line of thought is exploiting the molecular systems that regulate the innate tumor-homing activity of platelets, granulocytes, monocytes/macrophages, stem cells, endothelial-colony-forming cells, and red blood cells loaded with nanoparticles. This new vision springs from the results obtained with some of these cells in regenerative medicine, an approach called "cell therapy." This review takes into consideration the advantages of cell therapy as the only one capable of overcoming the limits of targeting imposed by the increased interstitial pressure of tumors.
靶向治疗和免疫治疗无疑改善了黑色素瘤患者的预后。然而，这种肿瘤的治疗仍需要具有更高治疗指数的方法，以减少与毒性作用和非特异性靶向相关的缺点。这意味着要开发由高亲和力分子衍生的治疗工具，这些分子针对黑色素瘤细胞中相对于其正常对应物差异表达的肿瘤成分。由于纳米颗粒具有高度可调节性，纳米医学试图解决这个问题。这种方法不仅利用了肿瘤微环境典型的增强渗透和滞留效应（被动靶向），还利用了识别某些肿瘤过表达分子的特定“分子天线”（主动靶向）。这一研究方向催生了所谓的“智能纳米颗粒”，其中一些已经通过临床前阶段，正在黑色素瘤患者中进行临床试验。为了进一步改善纳米颗粒在肿瘤内的分布，近年来有一种思路是利用调节血小板、粒细胞、单核细胞/巨噬细胞、干细胞、内皮集落形成细胞和负载纳米颗粒的红细胞固有肿瘤归巢活性的分子系统。这一新观点源于在再生医学中利用其中一些细胞所取得的成果，这种方法被称为“细胞疗法”。本综述考虑了细胞疗法的优势，因为它是唯一能够克服肿瘤间质压力增加所带来的靶向限制的方法。
