Palma, SICJ, Fernandes AR, Roque ACA.
2016.
An affinity triggered MRI nanoprobe for pH-dependent cell labeling, 2016. RSC Advances. 6(114):113503-113512.: The Royal Society of Chemistry
AbstractThe pH-sensitive affinity pair composed by neutravidin and iminobiotin was used to develop a multilayered Magnetic Resonance Imaging (MRI) nanoprobe responsive to the acidic pH of tumor microenvironment. The multilayer system was assembled on meso-2,3-dimercaptosuccinic acid-coated iron oxide magnetic nanoparticles (MNP), which convey negative MRI contrast enhancement properties to the nanoprobe. The outer stealth PEG-layer is altered in acidic media due to the disruption of interactions between neutravidin-iminobiotin. As a consequence, the positively charged inner layer is exposed and enhances interactions with cells. The nanoprobe uptake by HCT116 cells cultured in vitro under acidic conditions had a 2-fold increase compared to the uptake at physiological pH. The uptake difference is particularly clear in T2-weighted MRI phantoms of cells incubated with the nanoprobes at both pH conditions. This work sets the proof-of-concept of a MNP-based MRI nanoprobe targeting acidic tumor microenvironment through the use of a specific bio-recognition interaction that is pH-sensitive. This tumor targeting strategy is potentially applicable to the generality of tumors since the typical hypoxic conditions and high glycolysis rate in cancer cells create an acidic environment common to the majority of cancer types.
Pedrosa, P, Mendes R, Cabral R, Martins LMDRS, Baptista PV, Fernandes AR.
2018.
Combination of chemotherapy and Au-nanoparticle photothermy in the visible light to tackle doxorubicin resistance in cancer cells, 2018. Scientific Reports. 8(1):11429.
AbstractDespite great advances in the fight against cancer, traditional chemotherapy has been hindered by the dose dependent adverse side effects that reduce the usable doses for effective therapy. This has been associated to drug resistance in tumor cells that often cause relapse and therapy failure. These drawbacks have been tackled by combining different therapeutic regiments that prevent drug resistance while decreasing the chemotherapy dose required for efficacious ablation of cancer. In fact, new metallic compounds have been in a continuous development to extend the existing chemotherapy arsenal for these combined regimens. Here, we demonstrate that combination of a metallic compound (TS265), previously characterized by our group, with photothermy circumvents cells resistant to Doxorubicin (DOX). We first engendered a colorectal carcinoma cell line (HCT116) highly resistant to DOX, whose viability was diminished after administration of TS265. Cancer cell death was potentiated by challenging these cells with 14 nm spherical gold nanoparticles followed by laser irradiation at 532 nm. The combination of TS265 with photothermy lead to 65% cell death of the DOX resistant cells without impacting healthy cells. These results support the use of combined chemotherapy and photothermy in the visible spectrum as an efficient tool for drug resistant tumors.