Instituto de Investigação e Inovação em Saúde (A.R.S., M.J.O., B.S.), Instituto de Engenharia Biomédica (A.R.S., M.J.O., B.S.), Instituto de Ciências Biomédicas Abel Salazar (A.R.S., M.J.O.), and Faculdade de Medicina da (M.J.O.), Universidade do Porto, Porto, Portugal; Instituto Português de Oncologia do Porto, Porto, Portugal (A.R.S.); and Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde & Instituto Universitário de Ciências da Saúde, Gandra, Portugal (B.S.).
Instituto de Investigação e Inovação em Saúde (A.R.S., M.J.O., B.S.), Instituto de Engenharia Biomédica (A.R.S., M.J.O., B.S.), Instituto de Ciências Biomédicas Abel Salazar (A.R.S., M.J.O.), and Faculdade de Medicina da (M.J.O.), Universidade do Porto, Porto, Portugal; Instituto Português de Oncologia do Porto, Porto, Portugal (A.R.S.); and Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde & Instituto Universitário de Ciências da Saúde, Gandra, Portugal (B.S.)
J Pharmacol Exp Ther. 2019 Sep;370(3):657-670. doi: 10.1124/jpet.118.254441. Epub 2019 Jan 22.
Colorectal cancer (CRC) is one of the most common causes of cancer-related death in the world, mainly owing to distant metastasis events. Developing targeted strategies to treat and follow individuals in more developed stages is needed. The carcinoembryonic antigen (CEA) is a cell surface-overexpressed glycoprotein in most CRC patients, and the evaluation of its serum levels is recommended in the clinic. These reasons motivated the production of CEA-targeted nanotechnologies for monitorization of CRC progression, but only a few centers have reported their use for drug delivery. The cellular internalization of CEA-linked nanosystems occurs by the natural recycling of the CEA itself, enabling longer retention and sustained release of the cargo. The functionalization of nanoparticles with lower affinity ligands for CEA is possibly the best choice to avoid their binding to the soluble CEA. Here, we also highlight the use of nanoparticles made of poly(lactic--glycolic acid) (PLGA) polymer, a well known material, owing to its biocompatibility and low toxicity. This work offers support to the contribution of antibody fragment-functionalized nanoparticles as promising high affinity molecules to decorate nanosystems. The linkers and conjugation chemistries chosen for ligand-nanoparticle coupling will be addressed herein as an elements essential to the modulation of nanosystem features. This review, to our knowledge, is the first that focuses on CEA-targeted nanotechnologies to serve colorectal cancer therapy and monitorization.
结直肠癌（CRC）是世界上癌症相关死亡的最常见原因之一，主要归因于远处转移事件。需要开发针对这些事件的靶向治疗策略，并对处于更晚期的患者进行跟踪。癌胚抗原（CEA）是大多数 CRC 患者中细胞表面过表达的糖蛋白，临床推荐评估其血清水平。这些原因促使人们生产针对 CEA 的纳米技术来监测 CRC 的进展，但只有少数中心报告了其在药物输送方面的应用。CEA 连接的纳米系统的细胞内化是通过 CEA 自身的自然循环实现的，这使得货物的保留时间更长，释放更持续。用对 CEA 亲和力较低的配体对纳米颗粒进行功能化可能是避免与可溶性 CEA 结合的最佳选择。在这里，我们还强调了使用聚（乳酸-乙醇酸）（PLGA）聚合物制成的纳米颗粒，这是一种众所周知的材料，因为其具有生物相容性和低毒性。这项工作为抗体片段功能化纳米颗粒作为有前途的高亲和力分子来修饰纳米系统提供了支持。本文将讨论用于配体-纳米颗粒偶联的连接子和缀合化学，因为它们是调节纳米系统特性的重要元素。据我们所知，这是第一篇专门针对 CEA 靶向纳米技术用于结直肠癌治疗和监测的综述。
