Poly(2-alkyl-2-oxazoline)s are biocompatible polymers with polypeptide-isomeric structures that are attracting increasing interest as biomaterials for drug, gene, protein, and radionuclide delivery. They are, however, still relatively new in comparison to other classes of hydrophilic water-soluble polymers already established for such use, including poly(ethylene oxide), polyvinylpyrrolidone, and polymethacrylamides such as poly[N-(2-hydroxypropyl)methacrylamide]. This feature article critically compares the synthetic aspects and physicochemical and biological properties of poly(2-alkyl-2-oxazoline)s and these commonly studied polymers in terms of their suitability for biomedical applications.

The majority of the human genome encodes RNAs that do not code for proteins. These non-coding RNAs (ncRNAs) affect normal expression of the genes, including oncogenes and tumour suppressive genes, which make them a new class of targets for drug development in cancer. Although microRNAs (miRNAs) are the most studied regulatory ncRNAs to date, and miRNA-targeted therapeutics have already reached clinical development, including the mimics of the tumour suppressive miRNAs miR-34 and miR-16, which reached phase I clinical trials for the treatment of liver cancer and mesothelioma, the importance of long non-coding RNAs (lncRNAs) is increasingly being recognised. Here, we describe obstacles and advances in the development of ncRNA therapeutics and provide the comprehensive overview of the ncRNA chemistry and delivery technologies. Furthermore, we summarise recent knowledge on the biological functions of miRNAs and their involvement in carcinogenesis, and discuss the strategies of their therapeutic manipulation in cancer. We review also the emerging insights into the role of lncRNAs and their potential as targets for novel treatment paradigms. Finally, we provide the up-to-date summary of clinical trials involving miRNAs and future directions in the development of ncRNA therapeutics.

Magnetic resonance imaging using fluorinated contrast agents (F MRI) enables to achive highcontrast in images due to the negligible fluorine background in living tissues. In this pilot study, we developed new biocompatible, temperature-responsive, and easily synthesized polymeric nanogels containing a sufficient concentration of magnetically equivalent fluorine atoms for F MRI purposes. The structure of the nanogels is based on amphiphilic copolymers containing two blocks, a hydrophilic poly[ N-(2-hydroxypropyl)methacrylamide] (PHPMA) or poly(2-methyl-2-oxazoline) (PMeOx) block, and a thermoresponsive poly[ N(2,2difluoroethyl)acrylamide] (PDFEA) block. The thermoresponsive properties of the PDFEA block allow us to control the process of nanogel self-assembly upon its heating in an aqueous solution. Particle size depends on the copolymer composition, and the most promising copolymers with longer thermoresponsive blocks form nanogels of suitable size for angiogenesis imaging or the labeling of cells (approximately 120 nm). The in vitroF MRI experiments reveal good sensitivity of the copolymer contrast agents, while the nanogels were proven to be noncytotoxic for several cell lines.

Poly(2‐oxazoline)s (PAOx) represent an established class of polymer materials with a wide range of applications. In contrast, the homologous poly(2‐oxazine)s (PAOzi) are only gaining increasing attention in the past years. Despite their high synthetic modularity and excellent biological properties, reports describing their use as a platform for construction of drug delivery systems are still relatively sparse. In this report, an overview of the recent progress in the field of drug delivery systems based on PAOx and PAOzi polymers is provided and a comparison is made with systems based on other polymer carriers, particularly poly(ethylene glycol) (PEG) and poly(N‐hydroxypropylmethacrylamide) (PHPMA). The emerging potential of PAOx and PAOzi is highlighted in the context of current polymer therapeutics research.

In this report, monodisperse upconversion NaYF:Yb/Er nanoparticles with superior optical properties were synthesized by the oleic acid-stabilized high-temperature co-precipitation of lanthanide chlorides in octadec-1-ene as a high-boiling organic solvent. To render the particles with biocompatibility and colloidal stability in bioanalytically relevant phosphate buffered saline (PBS), they were modified by using in-house synthesized poly(ethylene glycol)-neridronate (PEG-Ner), a bisphosponate. The NaYF:Yb/Er@PEG nanoparticles showed excellent long-term stability in PBS and/or albumin without any aggregation or morphology transformation. The in vitro cytotoxicity of the nanoparticles was evaluated using primary fibroblasts (HF) and a cell line derived from human cervical carcinoma (HeLa). The particles were subsequently modified by using Bolton-Hunter-hydroxybisphosphonate to enable radiolabeling with I for single-photon emission computed tomography/computed tomography (SPECT/CT) bimodal imaging to monitor the biodistribution of the nanoparticles in non-tumor mice. The bimodal upconversionI-radiolabeled NaYF:Yb/Er@PEG nanoparticles are prospective for near-infrared (NIR) photothermal/photodynamic and SPECT/CT cancer theranostics.

Poly(2-alkyl-2-oxazoline)s (PAOx) are regaining interest for biomedical applications.H owever,t heir full potential is hampered by the inability to synthesise uniform high-molar mass PAOx. In this work, we proposed alternative intrinsic chain transfer mechanisms based on 2-oxazoline and oxazolinium chain-end tautomerisation and derived improved polymerization conditions to suppress chain transfer,allowing the synthesis of highly defined poly(2-ethyl-2-oxazoline)s up to ca. 50 kDa (dispersity () < 1.05) and defined polymers up to at least 300 kDa ( < 1.2). The determination of the chain transfer constants for the polymerisations hinted towards the tautomerisation of the oxazolinium chain end as most plausible cause for chain transfer.Finally,the method was applied for the preparation of up to 60 kDa molar mass copolymers of 2-ethyl-2-oxazoline and 2-methoxycarbonylethyl-2-oxazoline.

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