Recently, numerous polymer materials have been employed as drug carrier systems in medicinal research, and their detailed properties have been thoroughly evaluated. Water-soluble polymer carriers play a significant role between these studied polymer systems as they are advantageously applied as carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, antimicrobial molecules, or multidrug resistance inhibitors. Covalent attachment of carried molecules using a biodegradable spacer is strongly preferred, as such design ensures the controlled release of the drug in the place of a desired pharmacological effect in a reasonable time-dependent manner. Importantly, the synthetic polymer biomaterials based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are recognized drug carriers with unique properties that nominate them among the most serious nanomedicines candidates for human clinical trials. This review focuses on advances in the development of HPMA copolymer-based nanomedicines within the passive and active targeting into the place of desired pharmacological effect, tumors, inflammation or bacterial infection sites. Specifically, this review highlights the safety issues of HPMA polymer-based drug carriers concerning the structure of nanomedicines. The main impact consists of the improvement of targeting ability, especially concerning the enhanced and permeability retention (EPR) effect.

In this paper, we revised the current understanding of the protein corona that is created on the surface of nanoparticles in blood plasma after an intravenous injection. We have focused on nanoparticles that have a proven therapeutic outcome. These nanoparticles are based on two types of biocompatible amphiphilic copolymers based on N-(2-hydroxypropyl)methacrylamide (HPMA): a block copolymer, poly(ε-caprolactone) (PCL)-b-poly(HPMA), and a statistical HPMA copolymer bearing cholesterol moieties, which have been tested both in vitro and in vivo. We studied the interaction of nanoparticles with blood plasma and selected blood plasma proteins by electron paramagnetic resonance (EPR), isothermal titration calorimetry, dynamic light scattering, and cryo-transmission electron microscopy. The copolymers were labeled with TEMPO radicals at the end of hydrophobic PCL or along the hydrophilic HPMA chains to monitor changes in polymer chain dynamics caused by protein adsorption. By EPR and other methods, we were able to probe specific interactions between nanoparticles and blood proteins, specifically low- and high-density lipoproteins, immunoglobulin G, human serum albumin (HSA), and human plasma. It was found that individual proteins and plasma have very low binding affinity to nanoparticles. We observed no hard corona around HPMA-based nanoparticles; with the exception of HSA the proteins showed no detectable binding to the nanoparticles. Our study confirms that a classical “hard corona–soft corona” paradigm is not valid for all types of nanoparticles and each system has a unique protein corona that is determined by the nature of the NP material.

Targeted drug delivery using nano-sized carrier systems with targeting functions to malignant and inflammatory tissue and tailored controlled drug release inside targeted tissues or cells has been and is still intensively studied. A detailed understanding of the correlation between the pharmacokinetic properties and structure of the nano-sized carrier is crucial for the successful transition of targeted drug delivery nanomedicines into clinical practice. In preclinical research in particular, fluorescence imaging has become one of the most commonly used powerful imaging tools. Increasing numbers of suitable fluorescent dyes that are excitable in the visible to near-infrared (NIR) wavelengths of the spectrum and the non-invasive nature of the method have significantly expanded the applicability of fluorescence imaging. This chapter summarizes non-invasive fluorescence-based imaging methods and discusses their potential advantages and limitations in the field of drug delivery, especially in anticancer therapy. This chapter focuses on fluorescent imaging from the cellular level up to the highly sophisticated three-dimensional imaging modality at a systemic level. Moreover, we describe the possibility for simultaneous treatment and imaging using fluorescence theranostics and the combination of different imaging techniques, e.g., fluorescence imaging with computed tomography.

Galectin-3 (Gal-3) is a promising target in cancer therapy with a high therapeutic potential due to its abundant localization within the tumor tissue and its involvement in tumor development and proliferation. Potential clinical application of Gal-3-targeted inhibitors is often complicated by their insufficient selectivity or low biocompatibility. Nanomaterials based on N-(2-hydroxypropyl)methacrylamide (HPMA) nanocarrier are attractive for in vivo application due to their good water solubility and lack of toxicity and immunogenicity. Their conjugation with tailored carbohydrate ligands can yield specific glyconanomaterials applicable for targeting biomedicinally relevant lectins like Gal-3. In the present study we describe the synthesis and the structure-affinity relationship study of novel Gal-3-targeted glyconanomaterials, based on hydrophilic HPMA nanocarriers. HPMA nanocarriers decorated with varying amounts of Gal-3 specific epitope GalNAcβ1,4GlcNAc (LacdiNAc) were analyzed in a competitive ELISA-type assay and their binding kinetics was described by surface plasmon resonance. We showed the impact of various linker types and epitope distribution on the binding affinity to Gal-3. The synthesis of specific functionalized LacdiNAc epitopes was accomplished under the catalysis by mutant β-N-acetylhexosaminidases. The glycans were conjugated to statistic HPMA copolymer precursors through diverse linkers in a defined pattern and density using Cu(I)-catalyzed azide–alkyne cycloaddition. The resulting water-soluble and structurally flexible synthetic glyconanomaterials exhibited affinity to Gal-3 in low μM range. The results of this study reveal the relation between the linker structure, glycan distribution and the affinity of the glycopolymer nanomaterial to Gal-3. They pave the way to specific biomedicinal glyconanomaterials that target Gal-3 as a therapeutic goal in cancerogenesis and other disorders.