The ability to gain spatiotemporal information, and in some cases achieve spatiotemporal control, in the context of drug delivery makes theranostic fluorescent probes an attractive and intensely investigated research topic. This interest is reflected in the steep rise in publications on the topic that have appeared over the past decade. Theranostic fluorescent probes, in their various incarnations, generally comprise a fluorophore linked to a masked drug, in which the drug is released as the result of certain stimuli, with both intrinsic and extrinsic stimuli being reported. This release is then signaled by the emergence of a fluorescent signal. Importantly, the use of appropriate fluorophores has enabled not only this emerging fluorescence as a spatiotemporal marker for drug delivery but also has provided modalities useful in photodynamic, photothermal, and sonodynamic therapeutic applications. In this review we highlight recent work on theranostic fluorescent probes with a particular focus on probes that are activated in tumor microenvironments. We also summarize efforts to develop probes for other applications, such as neurodegenerative diseases and antibacterials. This review celebrates the diversity of designs reported to date, from discrete small-molecule systems to nanomaterials. Our aim is to provide insights into the potential clinical impact of this still-emerging research direction.
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http://dx.doi.org/10.1021/acs.chemrev.3c00778 | DOI Listing |
Drug Deliv Transl Res
January 2025
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland.
Functionalization of polymer nanoparticles (NPs) with targeting peptides is of interest for drug delivery applications to enhance tumor accumulation and penetration. Herein, we evaluated the feasibility of two different methods for the attachment of a tumor-penetrating peptide LinTT1 (AKRGARSTA) to poly(ethylene glycol)-block-poly(ε-caprolactone) (PCL-PEG) NPs: (1) "post-conjugation" onto pre-formed nanoparticles, and (2) "pre-conjugation", the synthesis and purification of peptide-polymer conjugates and subsequent nanoprecipitation of the conjugates diluted with non-functionalized polymers. Conjugation of the labelled peptide via maleimide-thiol chemistry was verified by gel permeation chromatography (GPC) and fluorescence measurements.
View Article and Find Full Text PDFEur J Surg Oncol
December 2024
Vrije Universiteit Brussel (VUB), Molecular Imaging and Therapy Research Group, MITH, Aartselaar 103, 1090, Brussels, Belgium.
Background: Fluorescence molecular imaging, a potent and non-invasive technique, has become indispensable in medicine for visualizing molecular processes. In surgical oncology, it aids treatment by allowing visualization of tumor cells during fluorescence-guided surgery (FGS). Targeting the urokinase plasminogen activator receptor (uPAR), overexpressed during tissue remodeling and inflammation, holds promise for advancing FGS by specifically highlighting tumors.
View Article and Find Full Text PDFBiomacromolecules
January 2025
Polymer Research Centre and Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Nadia, Mohanpur 741246, West Bengal, India.
The present investigation aims to develop a reactive oxygen species (ROS) and esterase-responsive biodegradable mannosylated polyurethane to effectively deliver the encapsulated antileishmanial drug amphotericin B (AmB) selectively to infected macrophage cells. Owing to suitable amphiphilic balance, the as-synthesized glycosylated polyurethane () with aryl boronic ester-based diol () moiety as ROS-trigger, water-soluble mannose pendants, and fluorescent 4,4-difluoro-4-bora-3a,4a-diaza--indacene (BODIPY) chain ends for bioimaging formed nanoaggregates in an aqueous medium as confirmed by H NMR spectroscopy, dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and critical aggregation concentration (CAC) measurements. Aided by two endogenous stimuli present in phagolysosome, ROS and esterase, AmB-encapsulated polymeric nanoaggregates as drug delivery vehicles achieved an efficient reduction of both and intracellular amastigote burden compared to the free AmB.
View Article and Find Full Text PDFEpilepsia
January 2025
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
Objective: Somatic variants causing epilepsy are challenging to detect, as they are only present in a subset of brain cells (e.g., mosaic), resulting in low variant allele frequencies.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Johns Hopkins University, Baltimore, MD, USA.
Background: By 2050 the number of Alzheimer's Disease (AD) patients is projected to exceed 150 million worldwide. AD is an incurable, insufficiently understood, and devastating neurodegenerative disease, with high patient heterogeneity in terms of progression, clinical manifestation (including neuropsychiatric symptoms, NPS) and, importantly, responsiveness to treatment options.[1] In the last 20 years, 98% of clinical trials for AD have failed, highlighting the urgent need to drastically change pre-clinical research to develop better predictors of drug safety and effectiveness.
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