RESUMO
The role of nanoparticles in cancer medicine is vast with debate still surrounding the distinction between therapeutic efficacy of actively targeted nanoparticles versus passively targeted systems for drug delivery. While it is commonly accepted that methodologies that result in homing a high concentration of drug loaded nanoparticles to the tumor is beneficial, the role of intracellular trafficking of these nanoparticles in dictating the overall therapeutic outcome remains unresolved. Herein we demonstrate that the therapeutic outcome of drug loaded nanoparticles is governed beyond simply enabling nanoparticle internalization in cells. Using two model polymeric nanoparticles, one decorated with the GE11 peptide for active targeting of the epidermal growth factor receptor (EGFR) and the other without, we demonstrate that EGFR mediated intracellular internalization results in an enhanced therapeutic effect compared to the nontargeted formulation. Our findings demonstrate that the intracellular destination of nanoparticles beyond its ability to internalize is an important parameter that has to be accounted for in the design of targeted drug delivery systems.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Docetaxel/farmacologia , Nanopartículas/química , Antineoplásicos/química , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Docetaxel/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Feminino , Humanos , Células MCF-7 , Nanopartículas/metabolismo , Tamanho da Partícula , Peptídeos/química , Peptídeos/metabolismo , Polímeros/química , Polímeros/metabolismo , Propriedades de SuperfícieRESUMO
Advances in nanotechnology have resulted in the design of effective, safe and tissue-selective nanocarriers for delivering therapeutics to treat malignancies, infections and other diseases. In pregnancy, nanoparticle-based drug formulations could have the potential to selectively target either the placenta and/or fetus, enabling 'fetal-friendly' drugs to be administered in pregnancy with minimal risk of off-target effects. A considerable amount of research has been carried out on maternal-placental-fetal nanoparticle uptake, transfer and toxicity using rodent and ex vivo models. However, the development of placental targeting strategies and the therapeutic evaluation of nanoformulations in pregnancy remains in its infancy. While some promising avenues are currently under investigation, much work is needed to bring the advantages of nanoparticle-based drug therapy in pregnancy to clinical reality.