Hyperbranched polyglycerol is one of the most widely studied biocompatible dendritic polymer and showed promising applications. Here, we summarized the recent advancements in the field.

We report the synthesis, characterization, activity, and biocompatibility of a novel series of antimicrobial peptide-polymer conjugates. Using parent peptide aurein 2.2, we designed a peptide array (∼100 peptides) with single and multiple W and R mutations and identified antimicrobial peptides (AMPs) with potent activity against Staphylococcus aureus (S. aureus). These novel AMPs were conjugated to hyperbranched polyglycerols (HPGs) of different molecular weights and number of peptides to improve their antimicrobial activity and toxicity. The cell and blood compatibility studies of these conjugates demonstrated better properties than those of the AMP alone. However, conjugates showed lower antimicrobial activity in comparison to that of peptides, as determined from minimal inhibition concentrations (MICs) against S. aureus, but considerably better than that of the available polymer-AMP conjugates in the literature. In addition to measuring MICs and characterizing the biocompatibility, circular dichroism spectroscopy was used to investigate the interaction of the novel conjugates with model bacterial biomembranes. Moreover, the novel conjugates were exposed to trypsin to evaluate their stability. It was found that the conjugates resist proteolysis in comparison with unprotected peptides. The peptide conjugates were active in serum and whole blood. Overall, the results show that combining a highly active AMP and low-molecular-weight HPG yields bioconjugates with excellent biocompatibility, MICs below 100 μg/mL, and proteolytic stability, which could potentially improve its utility for in vivo applications.

Chronic transfusion of red blood cells (RBCs) to patients with β-thalassemia, sickle cell disease, and other acquired anemic disorders generates significant amounts of bioactive iron deposits in the body. The inactivation and excretion of redox active iron(III) from the blood pool and organs are critical to prevent organ damage, and are the focus of iron chelation therapy (ICT) using low molecular weight Fe(III) specific chelators. However, the current ICT is suboptimal because of the short circulation time of chelators, toxicity, severe side effects, difficult regime of administration, and patient noncompliance. To address this issue, we have designed long circulating and biodegradable nanoconjugates with enhanced circulation time and well-defined biodegradability to improve iron excretion and avoid nonspecific organ accumulation. A series of iron chelating nanoconjugates were generated with deferoxamine (DFO) as the iron(III) specific chelator using polymer scaffolds containing structurally different acidic pH sensitive ketal groups. The type of degradation linkages used in the polymer scaffold significantly influenced the vascular residence time, biodistribution, and mode of excretion of chelators in mice. Remarkably, the conjugate, BGD-60 (140 kDa; R h , 10.6 nm; cyclic ketal), exhibited the long circulation half-life ( t 1/2β , 64 h), a 768-fold increase compared to DFO, and showed minimal polymer accumulation in major organs. The nanoconjugates were found to be nontoxic and excreted iron significantly better than DFO in iron overloaded mice. BGD-60 showed greater iron mobilization from plasma ( p = 0.0390), spleen ( p < 0.0001), and pancreas ( p < 0.0001) whereas BDD-200 (340 kDa; R h , 13.7 nm; linear ketal) mobilized iron significantly better from the spleen, liver, and pancreas ( p < 0.0001, p < 0.0001, and p < 0.0001, respectively) compared to DFO at equivalent doses. The nanoconjugate’s favorable long blood circulation time, biodegradability, and iron excretion profiles highlight their potential for future clinical translation.

Quantification of iron is an important step to assess the iron burden in patients suffering from iron overload diseases, as well as tremendous value in understanding the underlying role of iron in the pathophysiology of these diseases. Current iron determination of total or labile iron, requires extensive sample handling and specialized instruments, whilst being time consuming and laborious. Moreover, there is minimal to no overlap between total iron and labile iron quantification methodologies—i.e. requiring entirely separate protocols, techniques and instruments. Herein, we report a unified-ferene (u-ferene) assay that enables a 2-in-1 quantification of both labile and total iron from the same preparation of a biological specimen. We demonstrate that labile iron concentrations determined from the u-ferene assay is in agreement with confocal laser scanning microscopy techniques employed within the literature. Further, this assay offers the same sensitivity as the current gold standard, inductively coupled plasma mass spectrometry (ICP-MS), for total iron measurements. The new u-ferene assay will have tremendous value for the wider scientific community as it offers an economic and readily accessible method for convenient 2-in-1 measurement of total and labile iron from biological samples, whilst maintaining the precision and sensitivity, as compared to ICP-MS.

Iron is an essential mineral that serves as a prosthetic group for a variety of proteins involved in vital cellular processes. The iron economy within humans is highly conserved in that there is no proper iron excretion pathway. Therefore, iron homeostasis is highly evolved to coordinate iron acquisition, storage, transport, and recycling efficiently. A disturbance in this state can result in excess iron burden in which an ensuing iron-mediated generation of reactive oxygen species imparts widespread oxidative damage to proteins, lipids, and DNA. On the contrary, problems in iron deficiency either due to genetic or nutritional causes can lead to a number of iron deficiency disorders. Iron chelation strategies have been in the works since the early 1900s, and they still remain the most viable therapeutic approach to mitigate the toxic side effects of excess iron. Intense investigations on improving the efficacy of chelation strategies while being well tolerated and accepted by patients have been a particular focus for many researchers over the past 30 years. Moreover, recent advances in our understanding on the role of iron in the pathogenesis of different diseases (both in iron overload and iron deficiency conditions) motivate the need to develop new therapeutics. We summarized recent investigations into the role of iron in health and disease conditions, iron chelation, and iron delivery strategies. Information regarding small molecule as well as macromolecular approaches and how they are employed within different disease pathogenesis such as primary and secondary iron overload diseases, cancer, diabetes, neurodegenerative diseases, infections, and in iron deficiency is provided.