Abstract
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-co-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.
Footnotes
- Received October 16, 2018.
- Accepted January 18, 2019.
This work received financial support from the project [NORTE-01-0145-FEDER-000012], supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This project was also supported by FEDER–Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020–Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT–Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” [POCI-01-0145-FEDER-007274]. B.S. also holds funding from the CESPU/IINFACTS under the project NanoCEA-CESPU-2018. The authors declare no conflict of interest.
- Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics