Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation and one of the main causes of chronic disability worldwide with high prevalence in the ageing population. RA is characterized by autoantibody production, synovial inflammation and bone destruction, and the most accepted biomarker is rheumatoid factor (RF) autoantibodies. In this work, we developed a low-cost approach for the detection and quantification of the RF marker. This colorimetric immunosensor is based on gold nanoprobe crosslinking that results in extensive aggregation in the presence of the pentameric IgM RF. Aggregation of the nanoconjugates yields a color change from red to purple that can be easily observed by the naked eye. The interaction between nanoconjugates and the specific target was confirmed via dynamic light scattering (DLS), Raman spectroscopy and atomic force microscopy (AFM) imaging. This conceptual system shows a LOD of 4.15 UA mL(-1) IgM RF (clinical threshold is set for 20 IU mL(-1)). The one-step biosensor strategy herein proposed is much faster than conventional detection techniques, without the need for secondary antibodies, additional complex washing or signal amplification protocols. To the best of our knowledge this is the first report on target induced aggregation of gold nanoprobes for quantitative colorimetric autoantibody detection.

Nearly 1.5 million people worldwide suffer from chronic myeloid leukemia (CML), characterized by the genetic translocation t(9;22)(q34;q11.2), involving the fusion of the Abelson oncogene (ABL1) with the breakpoint cluster region (BCR) gene. Early onset diagnosis coupled to current therapeutics allow for a treatment success rate of 90, which has focused research on the development of novel diagnostics approaches. In this review, we present a critical perspective on current strategies for CML diagnostics, comparing to gold standard methodologies and with an eye on the future trends on nanotheranostics.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) represents the most common genetic subtype of adult ALL (20%-30%) and accounts for approximately 50% of all cases in the elderly. It has been considered the subgroup of ALL with the worst outcome. The introduction of tyrosine kinase inhibitors (TKIs) allows complete hematologic remission virtually in all patients, with improved disease-free survival and overall survival. Nevertheless, the emergence of resistant mutations in BCR-ABL1 may require different TKI strategies to overcome the patient's resistance and disease relapse. Here, we report a Ph+B-ALL case with persistent minimal residual disease (MRD) after treatment with dasatinib. The patient expressed the P190(BCR-ABL1) isoform and a novel BCR-ABL1 mutation, p.Y440C. The latter is in the C-terminal lobe of the kinase domain, which likely induces deviations in the protein structure and activity and destabilizes its inactive conformation. The treatment was substituted by bosutinib, which binds to the active conformation of the protein, prior to allogeneic bone marrow transplant to overcome the lack of a complete response to dasatinib. These findings strengthen the importance of BCR-ABL1 mutational screening in Ph+ patients, particularly for those who do not achieve complete molecular remission.

Introduction of tyrosine kinase inhibitors for chronic myeloid leukemia treatment is associated with a 63% probability of maintaining a complete cytogenetic response, meaning that over 30% patients require an alternative methodology to overcome resistance, tolerance, or side effects. Considering the potential of nanotechnology in cancer treatment and the benefits of a combined therapy with imatinib, a nanoconjugate was designed to achieve BCR-ABL1 gene silencing. Gold nanoparticles were functionalized with a single-stranded DNA oligonucleotide that selectively targets the e14a2 BCR-ABL1 transcript expressed by K562 cells. This gold (Au)-nanoconjugate showed great efficacy in gene silencing that induced a significant increase in cell death. Variation of BCL-2 and BAX protein expression, an increase of caspase-3 activity, and apoptotic bodies in cells treated with the nanoconjugate demonstrate its aptitude for inducing apoptosis on K562 BCR-ABL1-expressing cells. Moreover, the combination of the silencing Au-nanoconjugate with imatinib prompted a decrease of imatinib IC50. This Au-nanoconjugate was also capable of inducing the loss of viability of imatinib-resistant K562 cells. This strategy shows that combination of Au-nanoconjugate and imatinib make K562 cells more vulnerable to chemotherapy and that the Au-nanoconjugate alone may overcome imatinib-resistance mechanisms, thus providing an effective treatment for chronic myeloid leukemia patients who exhibit drug tolerance.

Nanotheranostics takes advantage of nanotechnology-based systems in order to diagnose and treat a specific disease. This approach is particularly relevant for personalized medicine, allowing the detection of a disease at an early stage, to direct a suitable therapy toward the target tissue based on the molecular profile of the altered phenotype, subsequently facilitating disease monitoring and following treatment. A tailored strategy also enables to reduce the off-target effects associated with universal treatments and improve the safety profile of a given treatment. The unique optical properties of gold nanoparticles, their ease of surface modification, and high surface-to-volume ratio have made them central players in this area. By combining imaging, targeting, and therapeutic agents in a single vehicle, these nanoconjugates are (ought to be) an important tool in the clinics. In this review, the multifunctionality of gold nanoparticles as theranostics agents will be highlighted, as well as the requirements before the translation of these nanoplatforms into routine clinical practice.

Nanotechnology has become a powerful approach to improve the way we diagnose and treat cancer. In particular, nanoparticles possess unique features for enhanced sensitivity and selectivity for earlier detection of circulating cancer biomarkers. In vivo, nanoparticles enhance the therapeutic efficacy of anticancer agents when compared to conventional chemotherapy, improving vectorization and delivery, and helping to overcome drug resistance. Nanomedicine has been mostly focused on solid cancers due to take advantage from the enhanced permeability and retention (EPR) effect experienced by tissues in the close vicinity of tumors, which enhance nanomedicine’s accumulation and, consequently, improve efficacy. Nanomedicines for leukemia and lymphoma, where EPR effect is not a factor, are addressed differently from solid tumors. Nevertheless, nanoparticles have provided innovative approaches to simple and non-invasive methodologies for diagnosis and treatment in liquid tumors. In this review, we consider the state of the art on different types of nanoconstructs for the management of liquid tumors, from pre-clinical studies to clinical trials. We also discuss the advantages of nanoplatforms for theranostics and the central role played by nanoparticles in this combined strategy.

Gold nanoparticles functionalized with thiolated oligonucleotides (Au-nanoprobes) have been used in a range of applications for the detection of bioanalytes of interest, from ions to proteins and DNA targets. These detection strategies are based on the unique optical properties of gold nanoparticles, in particular, the intense color that is subject to modulation by modification of the medium dieletric. Au-nanoprobes have been applied for the detection and characterization of specific DNA sequences of interest, namely pathogens and disease biomarkers. Nevertheless, despite its relevance, only a few reports exist on the detection of RNA targets. Among these strategies, the colorimetric detection of DNA has been proven to work for several different targets in controlled samples but demonstration in real clinical bioanalysis has been elusive. Here, we used a colorimetric method based on Au-nanoprobes for the direct detection of the e14a2 BCR-ABL fusion transcript in myeloid leukemia patient samples without the need for retro-transcription. Au-nanoprobes directly assessed total RNA from 38 clinical samples, and results were validated against reverse transcription-nested polymerase chain reaction (RT-nested PCR) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The colorimetric Au-nanoprobe assay is a simple yet reliable strategy to scrutinize myeloid leukemia patients at diagnosis and evaluate progression, with obvious advantages in terms of time and cost, particularly in low- to medium-income countries where molecular screening is not routinely feasible.