RESUMO
RESUMEN En años recientes hubo un auge del uso de terapias génicas para el tratamiento de enfermedades de gran incidencia, como el cáncer. Generalmente, estas se basan en la liberación de material genético como plásmidos, en el núcleo celular, con lo cual se corrige una función o se induce la producción de proteínas deficientes a nivel fisiológico. Para llevar a cabo la terapia génica se requiere de vectores capaces de encapsular el material genético y garantizar su entrega en el núcleo celular. Los polímeros catiónicos sintéticos han llamado la atención como vectores, debido a su capacidad de condensar ácidos nucleicos para formar partículas que los protegen de la degradación enzimática y facilitan su captación celular. La polietilenimina y el polimetacrilato de N, N-dimetilaminoetilo son los polímeros catiónicos más eficaces para la administración génica. Sin embargo, estos requieren modificaciones químicas específicas para eliminar o disminuir algunas limitaciones tales como su alta citotoxicidad y baja biodegradabilidad. En este artículo se analizan algunas de estas modificaciones, enfocándose en avances recientes en el desarrollo de copolímeros anfifílicos como precursores de nanopartículas usadas como vectores génicos.
SUMMARY During recent years, the use of genetic therapies has taken relevance in the treatment of high-incidence diseases such as cancer. Usually, they are based on the release of genetic material, as plasmids, into the cell nucleus, which corrects a function or induces the production of a deficient protein at the physiological level. To carry out gene therapy, vectors capable of encapsulating the genetic material and guaranteeing its delivery in the target cell nucleus are required. Synthetic cationic polymers have attracted great attention as vectors due to their ability to condense nucleic acids to form particles that protect them from enzymatic degradation and facilitate their cellular uptake. Polyethylenimine and poly (N, N-dimethylaminoethyl methacrylate) are the most effective cationic polymers for gene delivery. However, these polymers require specific chemical modifications to either avoid or diminish their high cytotoxicity and low biodegradability. This review analyzes some of these modifications, focusing on recent advances in the development of amphiphilic copolymers as precursors of nanoparticles used as gene vectors.
RESUMO
Multidrug resistance (MDR) in cancer cells is the development of resistance to a variety of structurally and functionally nonrelated anticancer drugs. This phenomenon has become a major obstacle to cancer chemotherapy seriously affecting the clinical outcome. MDR is associated with increased drug efflux from cells mediated by an energy-dependent mechanism involving the ATP-binding cassette (ABC) transporters, mainly P-glycoprotein (ABCB1), the MDR-associated protein-1 (ABCC1), and the breast cancer resistance protein (ABCG2). The first two transporters have been widely studied already and reviews summarized the results. The ABCG2 protein has been a subject of intense study since its discovery as its overexpression has been detected in resistant cell lines in numerous types of human cancers. To date, a long list of modulators of ABCG2 exists and continues to increase. However, little is known about the clinical consequences of ABCG2 modulation. This makes the design of novel, potent, and nontoxic inhibitors of this efflux protein a major challenge to reverse MDR and thereby increase the success of chemotherapy. The aim of the present review is to describe and highlight specific and nonspecific modulators of ABCG2 reported to date based on the selectivity of the compounds, as many of them are effective against one or more ABC transport proteins.
