Iridium-based Polymeric Multifunctional Imaging Tools for Biochemistry.

Herein, we report the development of a macromolecular multifunctional imaging tool for biological investigations, which is comprised of an N-(2-hydroxypropyl)methacrylamide backbone, iridium-based luminescent probe, glutamate carboxypeptidase II (GCPII) targeting ligand, and biotin affinity tag. The iridium luminophore is a tris-cyclometalated complex based on [Ir(ppy)] with one of its 2-phenylpyridine ligands functionalized to allow conjugation. Synthesized macromolecular probes differed in the structure of the polymer and content of the iridium complex.

Reinvestigation of the Automated Synthesis of Stoichiometrically Conjugated Antibodies to Access High Molecular Weight Payloads and Multiplexed Conjugation via an In-Solution Trans-Tagging Process.

Protein conjugates have found applications in a wide variety of fields, ranging from therapeutics to imaging and detection. However, robust control over the parameters of the conjugation process (such as sites and degree of conjugation) remains challenging. Previously, our group introduced Equimolar NAtive Chemical Tagging (ENACT), a method which allows for the monofunctionalization of proteins by combining an iterative low-conversion bioconjugation, an automated process, and a bioorthogonal trans-tagging reaction.

Evaluation of linear versus star-like polymer anti-cancer nanomedicines in mouse models.

Nanomedicines are considered next generation therapeutics with advanced therapeutic properties and reduced side effects. Herein, we introduce tailored linear and star-like water-soluble nanosystems as stimuli-sensitive nanomedicines for the treatment of solid tumors or hematological malignancies. The polymer carrier and drug pharmacokinetics were independently evaluated to elucidate the relationship between the nanosystem structure and its distribution in the body.

The transmission and toxicity of polymer-bound doxorubicin-containing exosomes derived from human adenocarcinoma cells.

Exosomes are extracellular vesicles with the ability to encapsulate bioactive molecules, such as therapeutics. This study identified a new exosome mediated route of doxorubicin and poly(N-(2-hydroxypropyl)methacrylamide) (pHPMA)-bound doxorubicin trafficking in the tumor mass. Exosome loading was achieved via incubation of the therapeutics with an adherent human breast adenocarcinoma cell line and its derived spheroids.

Structure-to-Efficacy Relationship of HPMA-Based Nanomedicines: The Tumor Spheroid Penetration Study.

Nanomedicines are a novel class of therapeutics that benefit from the nano dimensions of the drug carrier. These nanosystems are highly advantageous mainly within cancer treatment due to their enhanced tumor accumulation. Monolayer tumor cells frequently used in routine preclinical assessment of nanotherapeutics do not have a spatial structural architecture that allows the investigation of the penetration of nanomedicines to predict their behavior in real tumor tissue.

Coating Persistent Luminescence Nanoparticles With Hydrophilic Polymers for Imaging.

Persistent luminescence nanoparticles (PLNPs) are innovative nanomaterials highly useful for bioimaging applications. Indeed, due to their particular optical properties, i.e.

HPMA-based star polymer biomaterials with tuneable structure and biodegradability tailored for advanced drug delivery to solid tumours.

Design, controlled synthesis, physico-chemical and biological characteristics of novel well-defined biodegradable star-shaped copolymers intended for advanced drug delivery is described. These new biocompatible star copolymers were synthesised by grafting monodispersed semitelechelic linear (sL) N-(2-hydroxypropyl)methacrylamide copolymers onto a 2,2-bis(hydroxymethyl)propionic acid (bisMPA)-based polyester dendritic core of various structures. The hydrodynamic diameter of the star copolymer biomaterials can be tuned from 13 to 31 nm and could be adjusted to a given purpose by proper selection of the bisMPA dendritic core type and generation and by considering the sL copolymer molecular weight and polymer-to-core molar ratio.

N-(2-Hydroxypropyl)methacrylamide-Based Linear, Diblock, and Starlike Polymer Drug Carriers: Advanced Process for Their Simple Production.

We developed a new simplified method for the synthesis of well-defined linear, diblock, or starlike N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer drug carriers using controlled reversible addition-fragmentation chain transfer polymerization. The prepared monodispersed polymers are after the drug attachment intended for enhanced anticancer therapy. This new approach significantly reduces the number of required synthetic steps and minimizes the consumption of organic solvents during the synthesis.