Search

Melanin and polydopamine are potent biopolymers for the development of biomedical nanosystems. However, applications of melanin or polydopamine-based nanoparticles are limited by drawbacks related to a compromised colloidal stability over long time periods and associated cytotoxicity. To overcome these hurdles, a novel strategy is proposed that mimics the confinement of natural melanin in melanosomes. Melanosome mimics are developed by co-encapsulating the melanin/polydopamine precursors L-DOPA/dopamine with melanogenic enzyme Tyrosinase within polymersomes. The conditions of polymersome formation are optimized to obtain melanin/polydopamine polymerization within the cavity of the polymersomes. Similar to native melanosomes, polymersomes containing melanin/polydopamine show long-term colloidal stability, cell-compatibility, and potential for cell photoprotection. This novel kind of artificial melanogenesis is expected to inspire new applications of the confined melanin/polydopamine biopolymers., (© 2021 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)

How to precisely detect and effectively cure cancer which is defined as precise nanomedicine has drawn great attention worldwide. Polymeric nanoreactors which can in situ catalyze inert species into activated ones, can greatly increase imaging quality and enhance therapeutic effects along with decreased background interference and reduced serious side effects. After a brief introduction, the design and preparation of polymeric nanoreactors are discussed from the following aspects, that is, solvent-switch, pH-tuning, film rehydration, hard template, electrostatic interaction, and polymerization-induced self-assembly (PISA). Subsequently, the biomedical applications of these nanoreactors in the fields of cancer imaging, cancer therapy, and cancer theranostics are highlighted. The last but not least, conclusions and future perspectives about polymeric nanoreactors are given. It is believed that polymeric nanoreactors can bring a great opportunity for future fabrication and clinical translation of precise nanomedicine., (© 2021 Wiley-VCH GmbH.)

The use of glycopolymer-functionalized resins (Resin-Glc), as a solid support, in column mode for bacterial/protein capture and quantification is explored. The Resin-Glc is synthesized from commercially available chloromethylated polystyrene resin and glycopolymer, and is characterized by fourier transform infrared spectroscopy, thermogravimetry, and elemental analysis. The percentage of glycopolymer functionalized on Resin-Glc is accounted to be 5 wt%. The ability of Resin-Glc to selectively capture lectin, Concanavalin A, over Peanut Agglutinin, reversibly, is demonstrated for six cycles of experiments. The bacterial sequestration study using SYBR (Synergy Brands, Inc.) Green I tagged Escherichia coli/Staphylococcus aureus reveals the ability of Resin-Glc to selectively capture E. coli over S. aureus. The quantification of captured cells in the column is carried out by enzymatic colorimetric assay using methylumbelliferyl glucuronide as the substrate. The E. coli capture studies reveal a consistent capture efficiency of 10 5  CFU (Colony Forming Units) g -1 over six cycles. Studies with spiked tap water samples show satisfactory results for E. coli cell densities ranging from 10 2 to 10 7  CFU mL -1 . The method portrayed can serve as a basis for the development of a reusable solid support in capture and detection of proteins and bacteria., (© 2020 Wiley-VCH GmbH.)

Small molecular antioxidants are almost ineffective in regulating harmful oxidative stress in vivo because of their poor bioavailability. Polymer antioxidants are a promising alternative to address this issue, but their laborious synthetic routes limit their development. In this study, aliphatic and aromatic aldehydes are used to synthesize a family of polymers containing different α-aminophosphonate pendant groups via a facile one-pot method that combines the Kabachnik-Fields (KF) reaction and free radical polymerization. The structure-property relationship study of these polymers reveals the KF moieties in polymer structures confer radical scavenging ability on polymers. The radical scavenging ability and cytotoxicity of these polymers are evaluated in a stepwise manner to identify a biocompatible polymer antioxidant that can effectively protect the cells from H 2 O 2 -induced oxidative damage. This is the first attempt to develop antioxidative polymers by the KF reaction. It highlights the feasibility of synthesizing new functional polymers using multicomponent reactions, which has important implications for organic and polymer chemistry., (© 2020 Wiley-VCH GmbH.)

Mechanical properties and degradation profile are important parameters for the applications of biodegradable polyester such as poly(glycerol sebacate) in biomedical engineering. Here, a strategy is reported to make palmitate functionalized poly(glycerol sebacate) (PPGS) to alter the polymer hydrophobicity, crystallinity, microstructures and thermal properties. The changes of these intrinsic properties impart tunable degradation profiles and mechanical properties to the resultant elastomers depending on the palmitate contents. When the palmitates reach up to 16 mol%, the elastic modulus is tuned from initially 838 ± 55 kPa for the PGS to 333 ± 21 kPa for the PPGS under the same crosslinking conditions. The elastomer undergoes reversible elastic deformations for at least 1000 cycles within 20% strain without failure and shows enhanced elasticity. The polymer degradation is simultaneously inhibited because of the increased hydrophobicity. This strategy is different with other PGS modifications which could form a softer elastomer with less crosslinks but typically lead to a quicker degradation. Because the materials are made from endogenous molecules, they possess good cytocompatibility similar to the PGS control. Although these materials are designed specifically for small arteries, it is expected that they will be useful for other soft tissues too., (© 2020 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

The glycosaminoglycan heparin is a clinically important anticoagulant drug, primarily used to reduce the risk of blood clots (thrombosis) during surgery. Despite its importance in medicine and its continuous use over many decades, heparin suffers from several limitations associated with its heterogeneity and its extraction from animal tissues. In order to address these limitations, reversible addition-fragmentation chain transfer polymerization is utilized to prepare a library of heparin mimetic copolymers from the sulfonated monomers sodium 4-styrene sulfonate, potassium-3-sulfopropyl acrylate, potassium-3-sulfopropyl methacrylate, and sodium-2-acrylamido-2-methyl-1-propane sulfonate. Copolymers are prepared using combinations of two different monomers in various ratios. Monomer reactivity ratios are also determined for some representative monomer combinations, and all polymers are characterized by 1 H NMR spectroscopy and gel permeation chromatography. The anticoagulant activities of the copolymers are determined by activated partial thromboplastin time and thrombin clotting time assays and structure-activity relationships are explored., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photo/pH dual-responsive amphiphilic diblock copolymers with alkyne functionalized pendant o-nitrobenzyl ester group are synthesized using poly(ethylene glycol) as a macroinitiator. The pendant alkynes are functionalized as aldehyde groups by the azide-alkyne Huisgen cycloaddition. The anticancer drug doxorubicin (DOX) molecules are then covalently conjugated through acid-sensitive Schiff-base linkage. The resultant prodrug copolymers self-assemble into nanomicelles in aqueous solution. The prodrug nanomicelles have a well-defined morphology with an average size of 20-40 nm. The dual-stimuli are applied individually or simultaneously to study the release behavior of DOX. Under UV light irradiation, nanomicelles are disassembled due to the ONB ester photocleavage. The light-controlled DOX release behavior is demonstrated using fluorescence spectroscopy. Due to the pH-sensitive imine linkage the DOX molecules are released rapidly from the nanomicelles at the acidic pH of 5.0, whereas only minimal amount of DOX molecules is released at the pH of 7.4. The DOX release rate is tunable by applying the dual-stimuli simultaneously. In vitro studies against colon cancer cells demonstrate that the nanomicelles show the efficient cellular uptake and the intracellular DOX release, indicating that the newly designed copolymers with dual-stimuli-response have significant potential applications as a smart nanomedicine against cancer., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Targeting the distinct cholesterol metabolism of tumor cells is proposed as a novel way to treat tumors. Blocking acyl-CoA cholesterol acyltransferase-1 (ACAT-1) by the inhibitor avasimible (Ava), which elevates intracellular free cholesterol levels, is shown to effectively induce apoptosis. However, Ava faces disadvantages of poor water solubility, a short half-life, and no capability for fluorescence detection, which have greatly limited its application. Herein, a fluorescent hyperstar polymer (FHSP) is developed to encapsulate Ava to improve its ability to inhibit HeLa cells and K562 cells. The results of this study show that the obtained Ava-FHSP micelles possess a high drug loading capacity of 22.7% and bright green fluorescence. Ava and Ava-FHSP are cytotoxic to both HeLa and K562 cells and cause reductions in cell size, nuclear lysis, and chromatin condensation and hindered proliferation of both cell types by causing S phase cell cycle arrest. Further mechanistic analysis indicates that Ava-FHSP reduces the protein and messenger RNA expression of ACAT-1 and significantly increases intracellular free cholesterol levels, which can increase endoplasmic reticulum stress and finally cause cell apoptosis. All these results suggest that this fluorescent hyperstar polymer represents a potential therapeutic tumor strategy by changing the cholesterol metabolism of tumor cells., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The antimicrobial properties of polycations are strongly affected by the structural features such as the backbone flexibility and topology (isomerism) through the polymer ability to attain proper conformation in interaction with the cell membrane. In this paper, a synthesis and biocidal properties evaluation of ionenes characterized by different backbone topology (isomerism) and flexibility are presented. The findings reveal influence of variation in topology on activity against different microorganisms, and general positive effect of improved flexibility. Furthermore, one of the obtained ionenes displays degradable properties in near physiological environment (phosphate-buffered saline pH 7.4, 37 °C). The degradation proceeds via Hofmann elimination reaction and the products are not of acidic character. For the first time a new class of degradable ionenes with a high antimicrobial potential is presented., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Freestanding multilayer films prepared by layer-by-layer technique have attracted interest as promising materials for wound dressings. The goal is to fabricate freestanding films using chitosan (CHI) and alginate (ALG) including subsequent crosslinking to improve the mechanical properties of films while maintaining their biocompatibility. Three crosslinking strategies are investigated, namely use of calcium ions for crosslinking ALG, 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide combined with N-hydroxysuccinimide for crosslinking ALG with CHI, and Genipin for crosslinking chitosan inside the films. Different characteristics, such as surface morphology, wettability, swelling, roughness, and mechanical properties are investigated showing that films became thinner, exhibited rougher surfaces, had lower water uptake, and increased mechanical strength after crosslinking. Changes of wettability are moderate and dependent on the crosslinking method. In vitro cytotoxicity and cell attachment studies with human dermal fibroblasts show that freestanding CHI-ALG films represent a poorly adhesive substratum for fibroblasts, while studies using incubation of plastic-adherent fibroblast beneath floating films show no signs of cytotoxicity in a time frame of 7 days. Results from cell experiments combined with film characteristics after crosslinking, indicate that crosslinked freestanding films made of ALG and CHI may be interesting candidates for wound dressings., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Mucoadhesion is defined as the adherence of a synthetic or natural polymer to a mucosal membrane via physical or chemical interactions. Mucoadhesive materials are widely used to develop dosage forms for transmucosal drug delivery via ocular, nasal, esophageal, oral, vaginal, rectal, and intravesical routes of administration. This review will discuss some of the most prominent and recent synthetic methodologies employed to modify polymeric materials in order to enhance their mucoadhesive properties. This includes chemical conjugation of polymers with molecules bearing thiol-, catechol-, boronate-, acrylate-, methacrylate-, maleimide-, and N-hydroxy(sulfo)succinimide ester- groups., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Increasing recognition of the role of oxidative stress in the pathogenesis of many clinical conditions and the existence of defined redox potential in healthy tissues has led to extensive research in the development of redox-responsive materials for biomedical applications. Especially, considerable growth has been seen in the fabrication of polymeric nanogel-based drug delivery carriers utilizing redox-responsive cross-linkers bearing a variety of functional groups via various synthetic strategies. Redox-responsive polymeric nanogels provide an advantage of facile chemical modification post synthesis and exhibit a remarkable response to biological redox stimuli. Due to the interdisciplinary nature of the subject, a more profound combined conceptual knowledge from a chemical and biological point of view is imperative for the rational design of redox-responsive nanogels. The present review provides an insight into the design and fabrication of redox-responsive nanogels with particular emphasis on synthetic strategies utilized for the development of redox-responsive cross-linkers, polymerization techniques being followed for nanogel development and biomedical applications. Cooperative effect of redox trigger with other stimuli such as pH and temperature in the evolution of dual and triple stimuli-responsive nanogels is also discussed., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Dendritic polyglycerol-co-polycaprolactone (PG-co-PCL)-derived block copolymers are synthesized and explored as nanoscale drug delivery platforms for a chemotherapeutic agent, gemcitabine (GEM), which is the cornerstone of therapy for pancreatic ductal adenocarcinoma (PDAC). Current treatment strategies with GEM result in suboptimal therapeutic outcome owing to microenvironmental resistance and rapid metabolic degradation of GEM. To address these challenges, physicochemical and cell-biological properties of both covalently conjugated and non-covalently stabilized variants of GEM-containing PG-co-PCL architectures have been evaluated. Self-assembly behavior, drug loading and release capacity, cytotoxicity, and cellular uptake properties of these constructs in monolayer and in spheroid cultures of PDAC cells are investigated. To realize the covalently conjugated carrier systems, GEM, in conjunction with a tertiary amine, is attached to the polycarbonate block grafted from the PG-co-PCL core. It is observed that pH-dependent ionization properties of these amine side-chains direct the formation of self-assembly of block copolymers in the form of nanoparticles. For non-covalent encapsulation, a facile "solvent-shifting" technique is adopted. Fabrication techniques are found to control colloidal and cellular properties of GEM-loaded nanoconstructs. The feasibility and potential of these newly developed architectures for designing carrier systems for GEM to achieve augmented prognosis for pancreatic cancer are reported., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photodynamic therapy (PDT) is a promising cancer treatment approach. However, the photosensitizers (PS) used for PDT are often limited by their poor solubility and selectivity for tumors. The goal of this study is to improve water solubility and delivery of the photosensitizer 2-[1-hexyloxyethyl]-2-divinyl pyropheophorbide-a (HPPH) to breast cancer cells. An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-HPPH photosensitizer conjugate is synthesized with heat shock receptor glucose-regulated protein 78 (GRP78), targeting to GRP78 receptors of MCF-7 cells, which are upregulated under mild hyperthermia. It is found that the uptake of the GRP78 targeted pep-HPMA-HPPH copolymer conjugate in MCF-7 cells is improved through heat induction. Under mild hyperthermia the targeted copolymers are more effective compared to free HPPH. These results show potential for the utility of mild hyperthermia and copolymer delivery vehicles to enhance the efficacy of photodynamic therapy., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Amino acid ester substituted polyphosphazenes are osteoactive benefiting from their phosphorus-containing chemical structure, which highlights interests in bone tissue engineering. To correlate their chemical structures with cell activities, in this study, poly[(ethyl alanato) 0.3 (ethyl glycinato) 0.7 phosphazene] (PAGP) and poly[(ethyl phenylalanato) 0.3 (ethyl glycinato) 0.7 phosphazene] (PPGP) are synthesized to carry out studies on cell osteogenic differentiation. In the non-contact culture manner, bone mesenchymal stromal cells (BMSCs) are cultured in transwell chambers containing PAGP or PPGP films, while the cells and the materials do not contact. In the contact culture manner, BMSCs are cultured on the PAGP or PPGP films. In the meantime, solutions containing PAGP or PPGP degradation products (i.e., phosphate, ammonium, and corresponding amino acids) are applied for cell culture using inorganic phosphate (Pi) ion as control. Thus, the influences from substrate surface and degradation products can be identified separately. The results reveal that both the phosphorus-containing surface of PAGP and PPGP films and their degradation products play significant roles in regulating cell behaviors. In comparison with PAGP, PPGP seems able to provide relatively stable phosphorus-containing surface to strengthen the cell-scaffold interaction because of its slower degradation rate and higher Young's modulus, leading to greater promotion in osteogenic differentiation via contact effect., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The integration of additive manufacturing (AM) technology within biological systems holds significant potential, specifically when refining the methods utilized for the creation of in vitro models. Therefore, examination of cellular interaction with the physical/physicochemical properties of 3D-printed polymers is critically important. In this work, skeletal muscle (C 2 C 12 ), neuronal (SH-SY5Y) and hepatic (HepG2) cell lines are utilized to ascertain critical evidence of cellular behavior in response to 3D-printed candidate polymers: Clear-FL (stereolithography, SL), PA-12 (laser sintering, LS), and VeroClear (PolyJet). This research outlines initial critical evidence for a framework of polymer/AM process selection when 3D printing biologically receptive scaffolds, derived from industry standard, commercially available AM instrumentation. C 2 C 12 , SH-SY5Y, and HepG2 cells favor LS polymer PA-12 for applications in which cellular adherence is necessitated. However, cell type specific responses are evident when cultured in the chemical leachate of photopolymers (Clear-FL and VeroClear). With the increasing prevalence of 3D-printed biointerfaces, the development of rigorous cell type specific biocompatibility data is imperative. Supplementing the currently limited database of functional 3D-printed biomaterials affords the opportunity for experiment-specific AM process and polymer selection, dependent on biological application and intricacy of design features required., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In contrast to chemical routes, enzymatic polymerization possesses favorable characteristics of mild reaction conditions, few by-products, and high activity toward cyclic lactones which make it a promising technique for constructing polymeric materials. Meanwhile, it can avoid the trace residue of metallic catalysts and potential toxicity, and thus exhibits great potential in the biomedical fields. More importantly, lipase-catalyzed polymer synthesis usually shows favorable enantio-, regio-, and chemoselectivity. Here, the history and recent developments in lipase-catalyzed selective polymerization for constructing polymers with unique structures and properties are highlighted. In particular, the synthesis of polymeric materials which are difficult to prepare in a chemical route and the construction of polymers through the combination of selective enzymatic and chemical methods are focused. In addition, the future direction is proposed especially based on the rapid developments in computational chemistry and protein engineering techniques., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This paper presents the synthesis and characterization of d-fructose modified poly(ethylene glycol) (Fru-PEG) and fructose modified poly(ethylene glycol)-block-poly(ethyl hexyl glycidyl ether) (Fru-PEG-b-PEHG) that are both prepared by initiation with isopropyliden protected fructose, followed by deprotection of the sugar. The block copolymers are self-assembled into micelles, and are subsequently characterized by cryo-TEM and dynamic light scattering. The fluorescent dye Nile red is encapsulated as a model hydrophobic compound and fluorescent marker to perform initial uptake tests with breast cancer cells. The uptake of sugar and nonsugar decorated micelles is compared., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Telechelic antimicrobial poly(2-oxazoline)s with quaternary ammonium (quat) end groups are shown to be potent antimicrobial polymers against Gram-positive bacterial strains. In this study, the activity against the Gram-negative bacterium Escherichia coli is additionally implemented by hydrolyzing the poly(2-methyl-2-oxazoline) with two quart end groups to poly(ethylene imine) (PEI). The resulting telechelic polycations are active against Staphylococcus aureus and E. coli. The contribution of the PEI backbone is determined by measuring the antimicrobial activity in the presence of calcium ions. The influence of PEI on the overall activity strongly depends on the molecular weight and increases with higher mass. The PEI dominates the activity against E. coli at lower masses than against S. aureus. The quart end groups require an alkyl substituent of dodecyl or longer to dominate the antimicrobial activity. Additionally, PEI and quart end groups act synergistically., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Polymer masked-unmasked protein therapy (PUMPT) employs polymer conjugation to protect therapeutic proteins during transit through the bloodstream and allow controlled release at a disease site via triggered degradation of the polymeric component. Most reported PUMPT systems are based on the specific enzymatic degradation of the polymeric component to release the protein and reinstate its activity. In these cases, therapeutic output is dependent on the presence of the required enzyme at the disease site at a sufficiently high concentration. The present study aims to overcome this design limitation by using pH as the protein release trigger. An acidic-pH triggered PUMPT system is described herein employing biodegradable polyacetals (PAs) and trypsin as a model protein. While this system protects trypsin activity at the neutral pH of the bloodstream, acidic pH (characteristic of disease sites, tissue damage, or lysosomal compartments) contributes to PA degradation and the "unmasking" of protein activity., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Chloroquine-containing 2-(dimethylamino)ethyl methacrylate copolymers (PDCs) are synthesized by reversible addition-fragmentation chain-transfer polymerization. Systematic evaluation is performed to test the hypothesis that presence of chloroquine (CQ) in the PDC structure will improve miRNA delivery due to enhanced endosomal escape while simultaneously contribute to anticancer activity of PDC/miRNA polyplexes through inhibition of cancer cell migration. The results show that miRNA delivery efficiency is dependent both on the molecular weight and CQ. The best performing PDC/miRNA polyplexes show effective endosomal escape of miRNA. PDC polyplexes with therapeutic miR-210 show promising anticancer activity in human breast cancer cells. PDC/miRNA polyplexes show excellent ability to inhibit migration of cancer cells. Overall, this study supports the use of PDC as a promising polymeric drug platform for use in combination anti-metastatic and anticancer miRNA therapeutic strategies., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The synthesis and characterization of a family of nine pH-responsive, diblock copolymers designed to effectively deliver nucleic acids are reported. The stabilizing A block is comprised of an oligo(ethylene glycol) methyl ether methacrylate to impart water solubility. The cationic blocks of varying degrees of polymerization (DPs) are derived from three pH responsive, tertiary amine-containing methacrylates capable of complexing negatively charged nucleic acids. The cytotoxicity studies utilizing human embryonic kidney cells (HEK-293) and Michigan Cancer Foundation-7 (MCF-7) breast cancer cells indicate no decrease of cell viability with the diblock copolymers, with the exception of the two highest DPs of the cationic blocks with ethyl-substitutes tertiary amine. Gene knockdown experiments indicate high siRNA delivery and MYC gene knockdown in MCF-7 breast cancer cells for eight of the nine studied block copolymers. The results of the current study enable further development of the pH-responsive copolymer family for promising nucleic acid delivery vehicles applicable for clinical use., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Pseudouridine (Ψ) is an important urinary cancer biomarker, especially in human colorectal cancer (CRC). Disclosed herein is the first Ψ molecularly imprinted polymer (Ψ-MIP) material obtained from tailor-engineered functional monomers. The resulting MIP imprint exhibits a remarkable imprinting factor greater than 70. It is successfully used for the selective recognition of Ψ in spiked human urine. This selective functionalized material opens the route to the development of inexpensive disposable chemosensors for noninvasive CRC diagnosis and prognosis., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Polymeric drug delivery system termed as "polyprodrug amphiphile" poly(2-methylacryloyloxyethyl phosphorylcholine)-b-poly(10-hydroxy-camptothecin methacrylate (pMPC-b-pHCPT) is developed for the prolonged-acting cancer therapy. It is obtained by two-step reversible addition-fragmentation chain transfer polymerization of zwitterionic monomer MPC and an esterase-responsive polymerizable prodrug methacrylic anhydride-CPT, respectively. This diblock polymer is composed of both antifouling (pMPC) and bioactive (pHCPT) segments and the drug is designed as a building block to construct the polymer skeleton directly. Due to its distinct amphiphilicity, the polymer can self-assemble into micelles with different dynamic sizes by facilely tuning the ratio of MPC/HCPT under physiological conditions. The outer pMPC shell is superhydrophilic to form dense hydrate layer preventing the nanosystem from unwanted nonspecific protein adsorption, which is the main lead cause of the rapid clearance of nanoparticles in vivo, thus facilitating the accumulation of drugs in tumor sites via enhanced permeability and retention effect. The configuration of the polyprodrug amphiphile is confirmed by several measurements. The resistance to albumin adsorption, prolonged plasma retention time, accumulation in tumor sites, and anticancer activity of the micelles is also investigated in vitro and in vivo. This novel amphiphile can be expected as a promising agent for the passive targeted prolonged-acting cancer therapy., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Polymer nanomedicines are very attractive to improve the delivery of chemotherapeutics. Polymer conjugates and other polymer-based nanocarriers allow to increase plasma half-life and drug bioavailability and can also be guided toward tumors using passive and active targeting strategies. Since many chemotherapeutics act on targets that are located in well-defined subcellular compartments, other important factors that contribute to an efficient therapy include cellular internalization and subsequent intracellular trafficking of the polymer nanomedicines and/or its payload to the appropriate organelle in the cytoplasm. This article provides an overview of the different approaches that have been developed to control intracellular delivery of polymer nanomedicines and discusses the different techniques that can be used to monitor these processes., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aggregation-caused quenching (ACQ) is a general phenomenon that is faced by traditional fluorescent polymers. Aggregation-induced emission (AIE) is exactly opposite to ACQ. AIE molecules are almost nonemissive in their molecularly dissolved state, but they can be induced to show high fluorescence in the aggregated or solid state. Incorporation of AIE phenomenon into polymer design has yielded various polymers with AIE characteristics. In this review, the recent progress of AIE polymers for biological applications is summarized., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A multicomponent functional polymer is synthesized to support specific reactivity for successful conjugation with the vast array of functionality present in biological systems and the flexibility to conjugate biomolecules without requiring additional modification to install a terminal functional group. The multifunctional surface is realized using a novel coating composed of distinct N-hydroxysuccinimide (NHS) ester and benzoyl functionalities, which can provide accessibility to both the NHS ester-amine coupling reaction and the photochemically induced benzophenone crosslinking reaction, respectively. In addition, the multifunctional polymer is fabricated and transformed to form nanoscale colloids through the solvent displacement of a water/DMF system due to solubility characteristics of the resulting polymer with high polarity. A facile and efficient fabrication approach using the multifunctional nanocolloid is thus demonstrated to create a drug carrier by installing paclitaxel and folic acid for targeted cancer therapy., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Stimuli-sensitive polymeric vesicles or polymersomes as self-assembled colloidal nanocarriers have received paramount importance for their integral role as delivery system for therapeutics and biotherapeutics. This work describes spontaneous polymersome formation at pH 7, as evidenced by surface tension, steady state fluorescence, dynamic light scattering, and microscopic studies, by three hydrophilic random cationic copolymers synthesized using N,N-(dimethylamino)ethyl methacrylate (DMAEM) and methoxy poly(ethylene glycol) monomethacrylate in different mole ratios. The results suggest that methoxy poly(ethylene glycol) chains constitute the bilayer membrane of the polymersomes and DMAEM projects toward water constituting the positively charged surface. The polymersomes have been observed to release their encapsulated guest at acidic pH as a result of transformation into polymeric micelles. All these highly biocompatible cationic polymers show successful gene transfection ability as nonviral vector on human cell line with different potential. Thus these polymers prove their utility as a potential delivery system for hydrophilic model drug as well as genetic material., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Carbon nanotube (CNT)-hydrogel nanocomposites are beneficial for various biomedical applications, such as nerve regeneration, tissue engineering, sensing, or implant coatings. Still, there are impediments to developing nanocomposites, including attaining a homogeneous CNT-polymer dispersion or patterning CNTs on hydrogels. While few approaches have been reported for patterning CNTs on polymeric substrates, these methods include high temperature, high vacuum or utilize a sacrificial layer and, hence, are incompatible with hydrogels as they lead to irreversible collapse in hydrogel structure. In this study, a novel two-step method is designed to transfer CNTs onto hydrogels. First, dense CNTs are grown on quartz substrates. Subsequently, hydrogel solutions are deposited on the quartz-grown CNTs. Upon gelation, the hydrogel with transferred CNTs is peeled from the quartz. Successful transfer is confirmed by scanning electron microscopy and indirectly by cell attachment. The efficient transfer is attributed to π-interactions pregelation between the polymers in solution and the CNTs., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this contribution, amphiphilic star copolymers (H40-star-PCL-a-PEG) with an H40 hyperbranched polyester core and poly(ε-caprolactone)-a-poly(ethylene glycol) copolymer arms linked with acetal groups are synthesized using ring-opening polymerization and a copper (I)-catalyzed alkyne-azide cycloaddition click reaction. The acid-cleavable acetal groups between the hydrophilic and hydrophobic segments of the arms endow the amphiphilic star copolymers with pH responsiveness. In aqueous solution, unimolecular micelles can be formed with good stability and a unique acid degradability, as is desirable for anticancer drug carriers. For the model drug of doxorubicin, the in vitro release behavior, intracellular release, and inhibition of proliferation of HeLa cells show that the acid-cleavable unimolecular micelles with anticancer activity can be dissociated in an acidic environment and efficiently internalized by HeLa cells. Due to the acid-cleavable and biodegradable nature, unimolecular micelles from amphiphilic star copolymers are promising for applications in intracellular drug delivery for cancer chemotherapy., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Polymeric micelles (PM) have been extensively used for tumor-targeted delivery of hydrophobic anti-cancer drugs. The lipophilic core of PM is naturally suitable for loading hydrophobic drugs and the hydrophilic shell endows them with colloidal stability and stealth properties. Decades of research on PM have resulted in tremendous numbers of PM-forming amphiphilic polymers, and approximately a dozen micellar nanomedicines have entered the clinic. The first generation of PM can be considered solubilizers of hydrophobic drugs, with short circulation times resulting from poor micelle stability and unstable drug entrapment. To more optimally exploit the potential of PM for targeted drug delivery, several physical (e.g., π-π stacking, stereocomplexation, hydrogen bonding, host-guest complexation, and coordination interaction) and chemical (e.g., free radical polymerization, click chemistry, disulfide and hydrazone bonding) strategies have been developed to improve micelle stability and drug retention. In this review, the most promising physico-chemical approaches to enhance micelle stability and drug retention are described, and how these strategies have resulted in systems with promising therapeutic efficacy in animal models, paving the way for clinical translation, is summarized., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Three-armed poly(trimethylene carbonate) macromers with a relatively high molecular weight of 28.9 kg mol -1 are prepared by ring opening polymerization and subsequent functionalization with methacrylate end groups. A resin suitable for processing by stereolithography is developed using propylene carbonate as a diluent, a photoinitiator, and a dye to control the curing characteristics. The difficulties in building designed structures with digital light processing stereolithography and the ways of optimizing the resin compositions are described in detail. Using an optimized resin composition, which contained 50 wt% macromer, 50 wt% diluent, 0.05 wt% (relative to the macromer) dye, and 5 wt% (relative to the macromer) photoinitiator, designed 3D porous structures with a gyroid pore network geometry are manufactured. By varying pore sizes and porosities between, respectively, 300 and 1000 μm and 60% and 90%, cylindrical porous poly(trimethylene carbonate) network structures with compression moduli of 85-2320 kPa are prepared. A porous poly(trimethylene carbonate) network meniscus implant is designed on the basis of computed tomography imaging data. By adjusting the characteristics of the gyroid pore architecture, an implant with a compression modulus close to 400 kPa, which fits the compression modulus of human meniscal tissue, is manufactured by stereolithography., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Using suitable polymers as a carrier for growing and delivering retinal progenitor cells (RPCs) is a promising therapeutic strategy in retinal cell-replacement therapy. Herein recently developed polymer, poly(sebacoyl diglyceride) (PSeD), is selected and its nonhydroxylized counterpart poly(1,3-propylene sebacate) (PPS) is designed to evaluate their potentials for RPC growth and future RPC application. The structures and mechanical properties of the polymers are characterized. The cytocompatibility and effects of these polymers on RPC proliferation, differentiation, and migration are systematically investigated in vitro. Our data show that PPS and PSeD display excellent cytocompatibility with low expression of inflammation and apoptosis factors, which benefit RPC growth. In proliferation assays reveal that RPCs expands well on the polymers, but PPS performs the best for RPC expansion, indicating that PPS can remarkably promote RPC proliferation. In differentiation conditions, RPCs grown on PSeD are more likely to differentiate toward retinal neurons, including photoreceptors, the most interesting type of cells for retinal cell-replacement therapy. Additionally, our results demonstrate that RPCs grown on PSeD display an outstanding ability to migrate. In conclusion, PPS can markedly promote RPC proliferation, whereas PSeD can enhance RPC differentiation toward retinal neurons, suggesting that PSeD and PPS have potential applications in future retinal cell-replacement therapies., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Unlabelled: There is an actual need of advanced materials for the emerging field of bioelectronics. One commonly used material is the conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (, Pedot: PSS) due to its general use in organic electronics. However, depending on the application in bioelectronics,, Pedot: PSS is not fully biocompatible due to the high acidity of the residual sulfonate protons of PSS. In this paper, the synthesis and biocompatibility properties of new poly(3,4-ethylenedioxythiophene):GlycosAminoGlycan (, Pedot: GAG) aqueous dispersions and its resulting films are shown. Thus, negatively charged GAGs as an alternative to PSS are presented. Three different commercially available GAGs, hyaluronic acid, heparin, and chondroitin sulfate are used. Indeed,, Pedot: GAGs dispersions are prepared through an oxidative chemical polymerization in water. Biocompatibility assays of the, Pedot: GAGs coatings are performed using SH-SY5Y and CCF-STTG1 cell lines and with ATP and Ca(2+) . Results show full biocompatibility and a pronounced anti-inflammatory effect. This last characteristic becomes crucial if implanted in the body. These materials can be used for in vivo applications, as transistor or electrode for electrical recording and for all the possible situations when there is contact between electronic circuits and living tissues., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The use of light-sensitive polymers for the release of therapeutics is an important approach allowing the timing and amount of the release to be controlled precisely. The use of light has been pioneered to control insulin release from a dermal photoactivated depot, or PAD. One of the main impediments to the use of light-sensitive polymers in this context is the density of the materials: The large majority of the material is the carrier polymer, with the minority being the therapeutic. In this work, the feasibility of using insulin itself as a monomer in the polymerization process is demonstrated. Insulin modified with either one or two light cleavable azide groups is polymerized with a tridentate alkyne-bridging monomer using a click reaction. The resulting material called a "macropolymer" is ≈85% insulin, is insoluble in aqueous solvent, and releases native, soluble insulin upon irradiation., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The aim of this study is to design a polymeric nanogel system with tailorable degradation behavior. To this end, hydroxyethyl methacrylate-oligoglycolates-derivatized poly(hydroxypropyl methacrylamide) (pHPMAm-Gly-HEMA) and hydroxyethyl methacrylamide-oligoglycolates-derivatized poly(hydroxyethyl methacrylamide) (pHEMAm-Gly-HEMAm) are synthesized and characterized. pHEMAm-Gly-HEMAm shows faster hydrolysis rates of both carbonate and glycolate esters than the same ester groups of pHPMAm-Gly-HEMA. pHEMAm-Gly-HEMAm nanogels have tailorable degradation kinetics from 24 h to more than 4 d by varying their crosslink densities. It is shown that the release of a loaded macromolecular model drug is controlled by degradation of nanogels. The nanogels show similar cytocompatibility as PLGA nanoparticles and are therefore considered to be attractive systems for drug delivery., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Poly(2-alkenyl-2-oxazoline)s are promising functional polymers for a variety of biomedical applications, such as drug delivery systems, peptide conjugates, or gene delivery. In this study, poly(2-isopropenyl-2-oxazoline) (PIPOx) is prepared through free-radical polymerization initiated with azobisisobutyronitrile. Reactive 2-oxazoline units in the side chain support an addition reaction with different compounds containing a carboxylic group, which facilitates the preparation of polymers labeled with two different fluorescent dyes. The cytotoxicities of 2-oxazoline monomers, PIPOx, and fluorescently labeled PIPOx are evaluated in vitro using an 3-(4,5-Dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and ex vivo using a cell proliferation assay with adenosine triphosphate bioluminescence. The cell uptake of labeled PIPOx is used to determine the colocalization of PIPOx with cell organelles that are part of the endocytic pathway. For the first time, it is shown that poly(2-isopropenyl-2-oxazoline) is a biocompatible material and is suitable for biomedical applications; further, its immunomodulative properties are evaluated., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Pinosylvin is a natural stilbenoid known to exhibit antibacterial bioactivity against foodborne bacteria. In this work, pinosylvin is chemically incorporated into a poly(anhydride-ester) (PAE) backbone via melt-condensation polymerization, and characterized with respect to its physicochemical and thermal properties. In vitro release studies demonstrate that pinosylvin-based PAEs hydrolytically degrade over 40 d to release pinosylvin. Pseudo-first order kinetic experiments on model compounds, butyric anhydride and 3-butylstilbene ester, indicate that the anhydride linkages hydrolyze first, followed by the ester bonds to ultimately release pinosylvin. An antibacterial assay shows that the released pinosylvin exhibit bioactivity, while in vitro cytocompatibility studies demonstrate that the polymer is noncytotoxic toward fibroblasts. These preliminary findings suggest that the pinosylvin-based PAEs can serve as food preservatives in food packaging materials by safely providing antibacterial bioactivity over extended time periods., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This study reports the structural transition of electrospun poly(ε-caprolactone) (PCL)/poly[(propylmethacryl-heptaisobutyl-polyhedral oligomeric silsesquioxane)-co-(methyl meth-acrylate)] (POSS-MMA) blends, from PCL-rich fibers, to bicontinuous PCL core/POSS-MMA shell fibers, to POSS-MMA-rich fibers with a discontinuous PCL inner phase. A ternary phase diagram depicting the electrospinnability of PCL/POSS-MMA solutions is constructed by evaluating the morphological features of fibers electrospun from solutions with various concentrations and PCL/POSS-MMA blend ratios. X-ray diffraction, Raman spectroscopy, and differential scanning calorimetry are further used to characterize the electrospun PCL/POSS-MMA hybrid fibers. These physicochemical characterization results are thoroughly discussed to understand the internal structures of the hybrid fibers, which are directly correlated to the phase separation behavior of the electrospun solutions. The current study provides further insight into the complex phase behavior of POSS-copolymer-based systems, which hold great potential for a broad spectrum of biomedical applications., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Using different type of initiators, the antibacterial moieties are introduced at the chain end of poly(L,L-lactide) (PLLA) and poly(D,D-lactide) (PDLA), and the thermal properties are simultaneously improved using the stereocomplex approach. The physical interaction of polymers and antibacterial compounds is investigated. The double bonds at the chain end are utilized for the interaction of silver ion; however, the silver ions are not detected after stereocomplexation of PLLA and PDLA. On the other hand, catechin (CT) is selected as an initiator precursor of lactide polymerization, protecting the phenolic hydroxyl groups. The linear PLLA and PDLA are obtained by the initiator, resulting in CT conjugated PLAs at the chain end groups after deprotection of phenolic hydroxyl groups. The antibacterial properties are determined by proliferation tests of staphylococcus aureus. The results suggest that the antibacterial properties of CT modified PLAs are derived from the original CT parts., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The repair of large crushed or sectioned segments of peripheral nerves remains a challenge in regenerative medicine due to the complexity of the biological environment and the lack of proper biomaterials and architecture to foster reconstruction. Traditionally such reconstruction is only achieved by using fresh human tissue as a surrogate for the absence of the nerve. However, recent focus in the field has been on new polymer structures and specific biofunctionalization to achieve the goal of peripheral nerve regeneration by developing artificial nerve prostheses. This review presents various tested approaches as well their effectiveness for nerve regrowth and functional recovery., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Polylysine-b-p[HPMA] block copolymers containing a redox-responsive disulfide bond between both blocks are synthesized by RAFT polymerization of pentafluorphenyl-methacrylate with a macro-CTA from Nϵ-benzyloxycarbonyl (Cbz) protected polylysine (synthesized by NCA polymerization). This polylysine-b-p[PFMA] precursor block copolymer is converted to polylysine(Cbz)-b-p[HPMA] by postpolymerization modification with 2-hydroxypropylamine. After removal of the Cbz protecting group, cationic polylysine-b-p[HPMA] copolymers with a biosplittable disulfide moiety became available, which can be used as polymeric transfection vectors. These disulfide linked polylysine-S-S-b-p[HPMA] block copolymers show low cytotoxicity and increased transfection efficiencies (HEK-293T cells) compared to analogous blockcopolymers without disulfide group making them interesting for the transfection of sensitive immune cells., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The design and preparation of highly efficient drug delivery platforms using green methodologies is at the forefront of nanotherapeutics research. POxylated polyurea dendrimers are efficiently synthesized using a supercritical-assisted polymerization in carbon dioxide. These fluorescent, pH-responsive and water-soluble core-shell smart nanocarriers show low toxicity in terms of cell viability and absence of glutathione depletion, two of the major side effect limitations of current vectors. The materials are also found to act as good transfection agents, through a mechanism involving an endosomal pathway, being able to reduce 100-fold the IC50 of paclitaxel., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In the current study, well-defined polymer brushes are shown as an effective surface modification to resist the adhesion of whole blood and its components. Poly[oligo(ethylene glycol)methylether methacrylate] (poly(MeOEGMA)), poly(hydroxyethyl methacrylate) (poly(HEMA)), poly[N-(2-hydroxypropyl) methacrylamide] (poly(HPMA)), and poly(carboxybetaine acrylamide) (poly(CBAA)) brushes were grown by surface initiated atom transfer radical polymerization (SI-ATRP) and subsequently characterized by Fourier-transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), dynamic contact angle measurements, atomic force microscopy (AFM), and surface plasmon resonance (SPR) spectroscopy. All brushes decreased the fouling from blood plasma over 95% and prevented the adhesion of platelets, erythrocytes, and leukocytes as evidenced by SPR and SEM measurements., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bacterial phenotypes, such as biofilm formation, antibiotic resistance and virulence expression, are associated with quorum sensing. Quorum sensing is a density-dependent regulatory system of gene expression controlled by specific signal molecules, such as N-acyl homoserine lactones (AHLs), produced and released by bacteria. This study reports the development of linear polymers capable to attenuate quorum sensing by adsorption of AHLs. Linear polymers were synthesized using MMA as backbone monomer and methacrylic acid and itaconic acid as functional monomers. Two different quorum sensing-controlled phenotypes, Vibrio fischeri bioluminescence and Aeromonas hydrophila biofilm formation, were evaluated to test the polymers' efficiency. Results showed that both phenotypes were significantly affected by the polymers, with the itaconic acid-containing material being more effective than the methacrylic acid one. The polymer inhibitory effects were reverted by the addition of lactones, confirming attenuation of quorum sensing through sequestration of signal molecules. The polymers also showed no cytotoxicity when tested using a mammalian cell line., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Novel poly(ethylene glycol) and poly(N-(2-hydroxypropyl)methacrylamide) block copolymer (PEG-b-PHPMA) with well-defined composition was synthesized by RAFT polymerization. Folate and doxorubicin (DOX) were quantitatively introduced into the copolymer. The influences of folate content and pH value on folate receptor (FR) mediated cell endocytosis and pH-responsive DOX release were studied. It has been demonstrated that minimum folate content is needed for the enrichment of hydrophobic folate on the hydrophilic part of polymer conjugates. The cytotoxicity of targetable polymer drug conjugates was much higher than that of non-targetable ones and free DOX. It could be concluded that the folate plays a significant role in targeting and internalization of the conjugates against bladder cancer cells., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Polymeric nanostructures obtained through self-assembly of reduction-sensitive amphiphilic triblock copolymers were investigated as potential drug delivery systems. The characteristic feature of these polymers is their cleavable disulfide bond in the center of the hydrophobic block. Therefore, the triblock copolymers can be cleaved into amphiphilic diblock copolymers. A poly(2-hydroxyethyl methacrylate)-b-poly(butyl methacrylate)-S-S-poly(butyl methacrylate)-b-poly(2-hydroxyethyl methacrylate) (PHEMA-b-(PBMA-S-S-PBMA)-b-PHEMA) triblock copolymer was synthesized. It self-assembled into micelles which were used to encapsulate hydrophobic dye molecules (Nile Red, BodiPy 630/650) as model payloads. The self-assembled nanostructures disintegrated upon reduction of the disulfide bond, releasing their cargo and yielding larger particles that formed aggregates in solution after 24 h. A burst release of payload was shown within the first 15 min, followed by a constant release over several hours. As concentration gradients of reducing agents are commonly found in biological systems, the micelles could be used as redox-sensitive nanocarriers for the intracellular delivery of drugs., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photo-polymerizable scaffolds are designed and prepared via short chain poly(organo)phosphazene building blocks bearing glycine allylester moieties. The polyphosphazene was combined with a trifunctional thiol and divinylester in various ratios, followed by thiol-ene photo-polymerization to obtain porous matrices. Degradation studies under aqueous conditions showed increasing rates in correlation with the polyphosphazene content. Preliminary cell studies show the non-cytotoxic nature of the polymers and their degradation products, as well as the cell adhesion and proliferation of adipose-derived stem cells., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Surface engineered nanoparticles (NPs) are fabricated from polycaprolactone-polyethylenimine-folic acid (PCL-PEI-FA) and polycaprolactone-S-S-polyethylene glycol (PCL-S-S-PEG) copolymers. FESEM reveals the core-shell structure of these NPs of about 230 nm size. It is assumed that the inner cores of these NPs are composed of PCL, while the outer shells are adorned with PEG and folic acid, introducing a stealthy nature and specific targeting capability. Moreover, the disulfide bonds in the PCL-S-S-PEG copolymers provide a reduction-induced degradation characteristic in these NPs. Cell line experiments demonstrate the enhanced endocytosis and cytotoxicity of these NPs. Thus PCL-PEI-FA/PCL-S-S-PEG NPs could be a better candidate for the tumor specific delivery of hydrophobic drugs., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Multifunctional polymers with defined structure and biocompatibility are critical to the development of drug delivery systems and bioconjugates. In this article, the synthesis, in vitro blood compatibility, cell viability, in vivo circulation, biodistribution, and clearance of hybrid copolymers based on linear and branched polyglycerol are reported. Hybrid polyglycerols (M(n) ≈ 100 kDa) are synthesized with different compositions (15-80 mol% linear polyglycerol). Relatively small hydrodynamic size and radius of gyration of the hybrid polyglycerols suggest that they are highly compact functional nanostructures. The hybrid polyglycerols show excellent blood compatibility as determined by measuring their effects on blood coagulation, red blood cell aggregation, hemolysis, platelet, and complement activation. The cell viability in presence of hybrid polyglycerols is excellent up to 10 mg mL(-1) concentration and is similar to both dextran and polyvinyl alcohol. Furthermore, tritium labeled hybrid polyglycerol shows long blood circulation (t(1/2β)= 34 h) with minimal organ accumulation in mice. Multifunctionality, compact nature, biocompatibility, and the long blood circulation make these polymers attractive for the development of bioconjugates and drug delivery systems., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)