Redox-Responsive "Catch and Release" Cryogels: A Versatile Platform for Capture and Release of Proteins and Cells.

Macroporous cryogels are attractive scaffolds for biomedical applications, such as biomolecular immobilization, diagnostic sensing, and tissue engineering. In this study, thiol-reactive redox-responsive cryogels with a porous structure are prepared using photopolymerization of a pyridyl disulfide poly(ethylene glycol) methacrylate (PDS-PEG-MA) monomer. Reactive cryogels are produced using PDS-PEG-MA and hydrophilic poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) monomers, along with a PEG-based cross-linker and photoinitiator. Functionalization of cryogels using a fluorescent dye via the disulfide-thiol exchange reactions is demonstrated, followed by release under reducing conditions. For ligand-mediated protein immobilization, first, thiol-containing biotin or mannose is conjugated onto the cryogels. Subsequently, fluorescent dye-labeled proteins streptavidin and concanavalin A (ConA) are immobilized via ligand-mediated conjugation. Furthermore, we demonstrate that the mannose-decorated cryogel could capture ConA selectively from a mixture of lectins. The efficiency of protein immobilization could be easily tuned by changing the ratio of the thiol-sensitive moiety in the scaffold. Finally, an integrin-binding cell adhesive peptide is attached to cryogels to achieve successful attachment, and the on-demand detachment of integrin-receptor-rich fibroblast cells is demonstrated. Redox-responsive cryogels can serve as potential scaffolds for a variety of biomedical applications because of their facile synthesis and modification.

Metal-Free Click-Chemistry: A Powerful Tool for Fabricating Hydrogels for Biomedical Applications.

Increasing interest in the utilization of hydrogels in various areas of biomedical sciences ranging from biosensing and drug delivery to tissue engineering has necessitated the synthesis of these materials using efficient and benign chemical transformations. In this regard, the advent of "click" chemistry revolutionized the design of hydrogels and a range of efficient reactions was utilized to obtain hydrogels with increased control over their physicochemical properties. The ability to apply the "click" chemistry paradigm to both synthetic and natural polymers as hydrogel precursors further expanded the utility of this chemistry in network formation. In particular, the ability to integrate clickable handles at predetermined locations in polymeric components enables the formation of well-defined networks. Although, in the early years of "click" chemistry, the copper-catalyzed azide-alkyne cycloaddition was widely employed, recent years have focused on the use of metal-free "click" transformations, since residual metal impurities may interfere with or compromise the biological function of such materials. Furthermore, many of the non-metal-catalyzed "click" transformations enable the fabrication of injectable hydrogels, as well as the fabrication of microstructured gels using spatial and temporal control. This review article summarizes the recent advances in the fabrication of hydrogels using various metal-free "click" reactions and highlights the applications of thus obtained materials. One could envision that the use of these versatile metal-free "click" reactions would continue to revolutionize the design of functional hydrogels geared to address unmet needs in biomedical sciences.

Porous Microgels for Delivery of Curcumin: Microfluidics-Based Fabrication and Cytotoxicity Evaluation.

Polymeric microgels, fabricated via microfluidic techniques, have garnered significant interest as versatile drug delivery carriers. Despite the advances, the loading and release of hydrophobic drugs such as curcumin from polymeric microgels is not trivial. Herein, we report that effective drug loading can be achieved by the design of porous particles and the use of supramolecular cyclodextrin-based curcumin complexes. The fabrication of porous microgels through the judicious choice of chemical precursors under flow conditions was established. The evaluation of the curcumin loading dependence on the porosity of the microgels was performed. Microgels with higher porosity exhibited better curcumin loading compared to those with lower porosity. Curcumin-loaded microgels released the drug, which, upon internalization by U87 MG human glioma cancer cells, induced cytotoxicity. The findings reported here provide valuable insights for the development of tailored drug delivery systems using a microfluidics-based platform and outline a strategy for the effective delivery of hydrophobic therapeutic agents such as curcumin through supramolecular complexation.

Plug-and-Play Biointerfaces: Harnessing Host-Guest Interactions for Fabrication of Functional Polymeric Coatings.

Polymeric surface coatings capable of effectively integrating desired functional molecules and ligands are attractive for fabricating bio-interfaces necessary for various applications. Herein, we report the design of a polymeric platform amenable to such modifications in a modular fashion through host-guest chemistry. Copolymers containing adamantane (Ada) moieties, diethylene glycol (DEG) units, and silyloxy groups to provide functionalization handles, anti-biofouling character, and surface attachment, respectively, were synthesized. These copolymers were employed to modify silicon/glass surfaces to enable their functionalization using beta-cyclodextrin (ßCD) containing functional molecules and bioactive ligands. Moreover, surface functionalization could be spatially controlled using a well-established technique like microcontact printing. Efficient and robust functionalization of polymer-coated surfaces was demonstrated by immobilizing a ßCD-conjugated fluorescent rhodamine dye through the specific noncovalent binding between Ada and ßCD units. Furthermore, biotin, mannose, and cell adhesive peptide-modified ßCD were immobilized onto the Ada-containing polymer-coated surfaces to direct noncovalent conjugation of streptavidin, concanavalin A (ConA), and fibroblast cells, respectively. It was demonstrated that the mannose-functionalized coating could selectively bind to the target lectin ConA, and the interface could be regenerated and reused several times. Moreover, the polymeric coating was adaptable for cell attachment and proliferation upon noncovalent modification with cell-adhesive peptides. One can envision that the facile synthesis of the Ada-based copolymers, mild conditions for coating surfaces, and their effective transformation to various functional interfaces in a modular fashion offers an attractive approach to engineering functional interfaces for several biomedical applications.

pH-Responsive nanofiber buttresses as local drug delivery devices.

Electrospun nanofibers are a 3D scaffold of choice for many drug delivery devices due to their high surface area, significant capacity for drug payload, ease of in situ placement, and scalable manufacture. Herein, we report the synthesis of polymeric, pH-responsive nanofiber buttresses via electrospinning. The homopolymer is comprised of an acrylic backbone with acid-sensitive, hydrolyzable, trimethoxybenzaldehyde-protected side chains that lead to buttress transformation from a hydrophobic to a hydrophilic state under physiologically relevant pH conditions (e.g., extracellular tumor environment with pH = 6.5). Hydrolysis of the side chains leads to an increase in fiber diameter from approximately 350 to 900 nm and the release of the encapsulated drug cargo. In vitro drug release profiles demonstrate that significantly more drug is released at pH 5.5 compared to pH 7.4, thereby limiting the release to the target site, with docetaxel releasing over 20 days and doxorubicin over 7 days. Drug burst release, defined as >50% within 24 hours, does not occur at either pH or with either drug. Drug-loaded buttresses preserve drug activity and are cytotoxic to multiple human cancer lines, including breast and lung. Important to their potential application in surgical applications, the tensile strength of the buttresses is 6.3 kPa and, though weaker than commercially available buttresses, they provide sufficient flexibility and mechanical integrity to serve as buttressing materials via the application with a conventional surgical cutting stapler.

Molecularly Imprinted Polymer-Coated Inorganic Nanoparticles: Fabrication and Biomedical Applications.

Molecularly imprinted polymers (MIPs) continue to gain increasing attention as functional materials due to their unique characteristics such as higher stability, simple preparation, robustness, better binding capacity, and low cost. In particular, MIP-coated inorganic nanoparticles have emerged as a promising platform for various biomedical applications ranging from drug delivery to bioimaging. The integration of MIPs with inorganic nanomaterials such as silica (SiO2), iron oxide (Fe3O4), gold (Au), silver (Ag), and quantum dots (QDs) combines several attributes from both components to yield highly multifunctional materials. These materials with a multicomponent hierarchical structure composed of an inorganic core and an imprinted polymer shell exhibit enhanced properties and new functionalities. This review aims to provide a general overview of key recent advances in the fabrication of MIPs-coated inorganic nanoparticles and highlight their biomedical applications, including drug delivery, biosensor, bioimaging, and bioseparation.

"Clickable" Polymer Brush Interfaces: Tailoring Monovalent to Multivalent Ligand Display for Protein Immobilization and Sensing.

Facile and effective functionalization of the interface of polymer-coated surfaces allows one to dictate the interaction of the underlying material with the chemical and biological analytes in its environment. Herein, we outline a modular approach that would enable installing a variety of "clickable" handles onto the surface of polymer brushes, enabling facile conjugation of various ligands to obtain functional interfaces. To this end, hydrophilic anti-biofouling poly(ethylene glycol)-based polymer brushes are fabricated on glass-like silicon oxide surfaces using reversible addition-fragmentation chain transfer (RAFT) polymerization. The dithioester group at the chain-end of the polymer brushes enabled the installation of azide, maleimide, and terminal alkene functional groups, using a post-polymerization radical exchange reaction with appropriately functionalized azo-containing molecules. Thus, modified polymer brushes underwent facile conjugation of alkyne or thiol-containing dyes and ligands using alkyne-azide cycloaddition, Michael addition, and radical thiol-ene conjugation, respectively. Moreover, we demonstrate that the radical exchange approach also enables the installation of multivalent motifs using dendritic azo-containing molecules. Terminal alkene groups containing dendrons amenable to functionalization with thiol-containing molecules using the radical thiol-ene reaction were installed at the interface and subsequently functionalized with mannose ligands to enable sensing of the Concanavalin A lectin.

Fast-Forming Dissolvable Redox-Responsive Hydrogels: Exploiting the Orthogonality of Thiol-Maleimide and Thiol-Disulfide Exchange Chemistry.

Fast-forming yet easily dissolvable hydrogels (HGs) have potential applications in wound healing, burn incidences, and delivery of therapeutic agents. Herein, a combination of a thiol-maleimide conjugation and thiol-disulfide exchange reaction is employed to fabricate fast-forming HGs which rapidly dissolve upon exposure to dithiothreitol (DTT), a nontoxic thiol-containing hydrophilic molecule. In particular, maleimide disulfide-terminated telechelic linear poly(ethylene glycol) (PEG) polymer and PEG-based tetrathiol macromonomers are employed as gel precursors, which upon mixing yield HGs within a minute. The selectivity of the thiol-maleimide conjugation in the presence of a disulfide linkage was established through 1H NMR spectroscopy and Ellman's test. Rapid degradation of HGs in the presence of thiol-containing solution was evident from the reduction in storage modulus. HGs encapsulated with fluorescent dye-labeled dextran polymers and bovine serum albumin were fabricated, and their cargo release was investigated under passive and active conditions upon exposure to DTT. One can envision that the rapid gelation and fast on-demand dissolution under relatively benign conditions would make these polymeric materials attractive for a range of biomedical applications.

Redox-Responsive Hydrogels for Tunable and "On-Demand" Release of Biomacromolecules.

In recent years, stimuli-responsive degradation has emerged as a desirable design criterion for functional hydrogels to tune the release of encapsulated payload as well as ensure degradation of the gel upon completion of its function. Herein, redox-responsive hydrogels with a well-defined network structure were obtained using a highly efficient thiol-disulfide exchange reaction. In particular, gelation occurred upon combining thiol-terminated tetra-arm polyethylene glycol (PEG) polymers with linear telechelic PEG-based polymers containing pyridyl disulfide units at their chain ends. Rapid gelation proceeds with good conversions (>85%) to yield macroporous hydrogels possessing high water uptake. Furthermore, due to the presence of the disulfide linkages, the thus-obtained hydrogels can self-heal. The obtained hydrogels undergo complete degradation when exposed to environments rich in thiol-containing agents such as dithiothreitol (DTT) and L-glutathione (GSH). Also, the release profile of encapsulated protein, namely, bovine serum albumin, can be tuned by varying the molecular weight of the polymeric precursors. Additionally, it was demonstrated that complete dissolution of the hydrogel to rapidly release the encapsulated protein occurs upon treating these hydrogels with DTT. Cytotoxicity evaluation of the hydrogels and their degradation products indicated the benign nature of these hydrogels. Additionally, the cytocompatible nature of these materials was also evident from a live/dead cell viability assay. One can envision that the facile fabrication and their ability to degrade on-demand and release their payload will make these benign polymeric scaffolds attractive for various biomedical applications.

Dermal delivery and follicular targeting of adapalene using PAMAM dendrimers.

Acne is a chronic dermatological disease of pilosebaceous units existing in the form of hair follicles (HFs) and accompanying sebaceous glands. In topical acne treatment, localisation of drug substance at the target site, in pilosebaceous units, especially in HFs is essential. The aims of this study were to develop and optimise adapalene (ADA)-loaded PAMAM dendrimer-based nanocarriers for topical acne treatment and to prepare gel formulations of the selected nanocarriers and to characterise their rheological properties and spreadability. ADA accumulation in HFs and in the skin from PAMAM dendrimers' aqueous colloidal formulations and their gel formulations were quantitatively determined using punch biopsy technique. Follicular targeting efficiency from PAMAM dendrimers and their gel formulation was compared with the commercial gel product, Differin® Gel. The localisation of fluorescently labelled PAMAM dendrimers was visualised using a confocal microscope, which confirmed a successful delivery of the carrier system to the HFs. It was also quantified that PAMAM dendrimers improved follicular localisation and skin deposition of ADA. PAMAM dendrimers' gel formulation including lower ADA doses compared with the commercial product exhibited efficient performance in terms of drug accumulation in HFs. In vitro cell viability studies showed the relative safety of G2-PAMAM dendrimers which could be considered to possibly be well tolerated by the skin. Overall, PAMAM dendrimers' potential to selectively target drugs to the site of action, reduce dose administrated, therefore minimise side effects and provide efficiency in topical treatment of dermatological diseases such as acne was shown.

Photothermally Active Cryogel Devices for Effective Release of Antimicrobial Peptides: On-Demand Treatment of Infections.

There has been significant interest in the use of peptides as antimicrobial agents, and peptide containing hydrogels have been proposed as biological scaffolds for various applications. Limited stability and rapid clearance of small molecular weight peptides pose challenges to their widespread implementation. As a common approach, antibacterial peptides are physically loaded into hydrogel scaffolds, which leads to continuous release through the passive mode with spatial control but provides limited control over drug dosage. Although utilization of peptide covalent linkage onto hydrogels addresses partially this problem, the peptide release is commonly too slow. To alleviate these challenges, in this work, maleimide-modified antimicrobial peptides are covalently conjugated onto furan-based cryogel (CG) scaffolds via the Diels-Alder cycloaddition at room temperature. The furan group offers a handle for specific loading of the peptides, thus minimizing passive and burst drug release. The porous nature of the CG matrix provides rapid loading and release of therapeutic peptides, apart from high water uptake. Interfacing the peptide adduct containing a CG matrix with a reduced graphene oxide-modified Kapton substrate allows "on-demand" photothermal heating upon near-infrared (NIR) irradiation. A fabricated photothermal device enables tunable and efficient peptide release through NIR exposure to kill bacteria. Apart from spatial confinement offered by this CG-based bandage, the selective ablation of planktonic Staphylococcus aureus is demonstrated. It can be envisioned that this modular "on-demand" peptide-releasing device can be also employed for other topical applications by appropriate choice of therapeutic peptides.

An 'on-demand' photothermal antibiotic release cryogel patch: evaluation of efficacy on an ex vivo model for skin wound infection.

A myriad of topical therapies and dressings are available to the clinicians for wound healing skin, but only a very few have shown their effectiveness in promoting wound repair due to challenges in controlling drug release. To address this issue, in this work, a near infrared (NIR)-light activable cryogel based on butyl methacrylate (BuMA) and poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) incorporated with reduced graphene oxide (rGO) was fabricated. The obtained cryogel provides the required hydrophilicity beneficial for wound treatment. The excellent photo-thermal properties of rGO allow for heating the cryogel, which results in subsequent swelling of the cryogel (CG) followed by release of the encapsulated drug load, cefepime in our case. Without photothermal activation, no release of payload was observed. The potential of this bandage for wound healing was examined using an ex vivo human skin model infected with Staphylococcus aureus (S. aureus). Apart from the efficacy of the cryogel based wound healing system, our results also suggest that the ex vivo wound model evaluated here provides a rapid and valuable tool to study superficial skin infections in humans and test the efficacy of antimicrobial agents.

Thiol-Reactive Clickable Cryogels: Importance of Macroporosity and Linkers on Biomolecular Immobilization.

Macroporous cryogels that are amenable to facile functionalization are attractive platforms for biomolecular immobilization, a vital step for fabrication of scaffolds necessary for areas like tissue engineering and diagnostic sensing. In this work, thiol-reactive porous cryogels are obtained via photopolymerization of a furan-protected maleimide-containing poly(ethylene glycol) (PEG)-based methacrylate (PEGFuMaMA) monomer. A series of cryogels are prepared using varying amounts of the masked hydrophilic PEGFuMaMA monomer, along with poly(ethylene glycol) methyl ether methacrylate and poly(ethylene glycol) dimethacrylate, a hydrophilic monomer and cross-linker, respectively, in the presence of a photoinitiator. Subsequent activation to the thiol-reactive form of the furan-protected maleimide groups is performed through the retro Diels-Alder reaction. As a demonstration of direct protein immobilization, bovine serum albumin is immobilized onto the cryogels. Furthermore, ligand-directed immobilization of proteins is achieved by first attaching mannose- or biotin-thiol onto the maleimide-containing platforms, followed by ligand-directed immobilization of concanavalin A or streptavidin, respectively. Additionally, we demonstrate that the extent of immobilized proteins can be controlled by varying the amount of thiol-reactive maleimide groups present in the cryogel matrix. Compared to traditional hydrogels, cryogels demonstrate enhanced protein immobilization/detection. Additionally, it is concluded that utilization of a longer linker, distancing the thiol-reactive maleimide group from the gel scaffold, considerably increases protein immobilization. It can be envisioned that the facile fabrication, conjugation, and control over the extent of functionalization of these cryogels will make these materials desirable scaffolds for numerous biomedical applications.

Multifunctional and Transformable 'Clickable' Hydrogel Coatings on Titanium Surfaces: From Protein Immobilization to Cellular Attachment.

Multifunctionalizable hydrogel coatings on titanium interfaces are useful in a wide range of biomedical applications utilizing titanium-based materials. In this study, furan-protected maleimide groups containing multi-clickable biocompatible hydrogel layers are fabricated on a titanium surface. Upon thermal treatment, the masked maleimide groups within the hydrogel are converted to thiol-reactive maleimide groups. The thiol-reactive maleimide group allows facile functionalization of these hydrogels through the thiol-maleimide nucleophilic addition and Diels-Alder cycloaddition reactions, under mild conditions. Additionally, the strained alkene unit in the furan-protected maleimide moiety undergoes radical thiol-ene reaction, as well as the inverse-electron-demand Diels-Alder reaction with tetrazine containing molecules. Taking advantage of photo-initiated thiol-ene 'click' reactions, we demonstrate spatially controlled immobilization of the fluorescent dye thiol-containing boron dipyrromethene (BODIPY-SH). Lastly, we establish that the extent of functionalization on hydrogels can be controlled by attachment of biotin-benzyl-tetrazine, followed by immobilization of TRITC-labelled ExtrAvidin. Being versatile and practical, we believe that the described multifunctional and transformable 'clickable' hydrogels on titanium-based substrates described here can find applications in areas involving modification of the interface with bioactive entities.

Trastuzumab targeted micellar delivery of docetaxel using dendron-polymer conjugates.

Incorporation of a therapeutic antibody into nanosized drug delivery systems can improve their target specificity. This work reports an antibody-conjugated targeted delivery system composed of polymer-dendron conjugates. Trastuzumab is chosen as the targeting moiety, since it is clinically used against tumor cells expressing HER2 receptors. A micellar delivery system was generated using amphiphilic polymer-dendron conjugates containing a fourth-generation polyester dendron as the hydrophobic block and a linear poly(ethylene glycol) (PEG) chain as the hydrophilic block. After preparation of docetaxel loaded (ca. 10% wt) micelles, trastuzumab was conjugated onto the micellar shell using an amidation reaction. Micelles remained stable after conjugation of the antibody, with a slight increase in size from 179 nm to 185 nm upon functionalization. Docetaxel release was determined to be responsive to acidic pH, and over the course of 30 h, 54% drug release was measured in acidic media, whereas it was around 30% under neutral conditions. Cytotoxicity experiments on MCF-7 and SK-OV-3 cell lines displayed improved toxicity levels for targeted micelles in comparison with the non-targeted counterparts, whereas pulse-chase experiments indicated effectiveness of micellar formulations and the presence of targeting groups. Cellular internalization experiments using fluorescence microscopy and flow cytometry further demonstrated the enhanced cellular uptake of antibody conjugated targeted micelles.

Fabrication of Patterned Hydrogel Interfaces: Exploiting the Maleimide Group as a Dual Purpose Handle for Cross-Linking and Bioconjugation.

Functional hydrogels that can be obtained through facile fabrication procedures and subsequently modified using straightforward reagent-free methods are indispensable materials for biomedical applications such as sensing and diagnostics. Herein a novel hydrogel platform is obtained using polymeric precursors containing the maleimide functional group as a side chain. The maleimide groups play a dual role in fabrication of functional hydrogels. They enable photochemical cross-linking of the polymers to yield bulk and patterned hydrogels. Moreover, the maleimide group can be used as a handle for efficient functionalization using the thiol-maleimide conjugation and Diels-Alder cycloaddition click reactions. Obtained hydrogels are characterized in terms of their morphology, water uptake capacity, and functionalization. Micropatterned hydrogels are obtained under UV-irradiation using a photomask to obtain reactive micropatterns, which undergo facile functionalization upon treatment with thiol-containing functional molecules such as fluorescent dyes and bioactive ligands. The maleimide group also undergoes conjugation through the Diels-Alder reaction, where the attached molecule can be released through thermal treatment via the retro Diels-Alder reaction. The antibiofouling nature of these hydrogel micropatterns enables efficient ligand-directed biomolecular immobilization, as demonstrated by attachment of streptavidin-coated quantum dots.

Orthogonally "Clickable" Biodegradable Nanofibers: Tailoring Biomaterials for Specific Protein Immobilization.

Multifunctionalizable polymeric nanofibers can be tailored for various biomedical applications by selective conjugation of small molecules and bioactive ligands. This study reports the design, synthesis, and application of novel biodegradable polyester-based nanofibers bearing metal-free "clickable" handles. Polylactide-based polymers were synthesized using organo-catalyzed ring-opening polymerization to contain "clickable" chain-end functional groups that specifically react through radical or nucleophilic thiol-ene reactions. A furan-protected maleimide-containing hydroxyl-bearing initiator yielded polymers containing strained oxanorbornene unit at their chain end. In addition, postpolymerization thermal treatment provides maleimide end group-containing polymers. Solution electrospinning method was utilized to obtain bead-free nanofibers. Efficient conjugation on these nanofibers was demonstrated using metal-free conjugation reactions. It was observed that polylactide nanofibers undergo extensive biofouling, which limits their possible utilization for specific biomolecular immobilization. To alleviate this problem, polymers were modified to contain two orthogonally reactive functional groups, namely, the oxanorbornene unit and an azide group at their chain ends. The former reactive handle was used for conjugation of poly(ethylene glycol) chains to impart hydrophilicity and thus an antibiofouling ability, whereas the azide group undergoes strain-promoted azide-alkyne cycloaddition to install a protein-binding ligand such as biotin. These nanofibers were able to specifically immobilize the protein streptavidin with minimal nonspecific adsorption.

Dendron-Polymer Conjugate Based Cross-Linked Micelles: A Robust and Versatile Nanosystem for Targeted Delivery.

Among various nanomedicine platforms, biodegradable polymeric micelles offer a viable approach to targeted cancer therapy. Herein, we report fabrication of core-cross-linked micelles using dendron-polymer conjugates as building blocks. Hydrophobic polyester dendrons containing peripheral alkene groups are conjugated to a hydrophilic poly(ethylene glycol) based copolymer bearing activated ester groups for appending an amine-containing peptide based targeting group, namely, cRGDfK. Micellar constructs assembled in aqueous media were cross-linked using a tetra-thiol molecule via the photochemical thiol-ene reaction. Cross-linked and non-cross-linked micelles were compared in terms of their critical micellar concentration, stability, drug loading, and drug release characteristics. It was observed that the cross-linked micelles were stable upon excessive dilution compared to their non-cross-linked counterparts. Importantly, the amount of passive drug release in neutral pH was considerably lower for the cross-linked micellar systems. Furthermore, treatment of MDA-MB-231 breast cancer cells with nontargeted and targeted cross-linked micelles demonstrated higher internalization of the targeted construct. In corroboration, in vitro assay revealed that drug loaded targeted micelles possessed higher cytotoxicity than the nontargeted ones. Facile fabrication of this modular platform which can carry a desired therapeutic agent and be conjugated with appropriate targeting units, along with the attributes necessary to serve as a viable drug delivery system, offers a platform with potential for addressing various challenges in the field of micellar drug delivery.

Reduced Graphene-Oxide-Embedded Polymeric Nanofiber Mats: An "On-Demand" Photothermally Triggered Antibiotic Release Platform.

The steady increase of antimicrobial resistance of different pathogens requires the development of alternative treatment strategies next to the oral delivery of antibiotics. A photothermally activated platform based on reduced graphene oxide (rGO)-embedded polymeric nanofiber mats for on-demand release of antibiotics upon irradiation in the near-infrared is fabricated. Cross-linked hydrophilic nanofibers, obtained by electrospinning a mixture of poly(acrylic acid) (PAA) and rGO, show excellent stability in aqueous media. Importantly, these PAA@ rGO nanofiber mats exhibit controlled photothermal heating upon irradiation at 980 nm. Nanofiber mats are efficiently loaded with antibiotics through simple immersion into corresponding antibiotics solutions. Whereas passive diffusion based release at room temperature is extremely low, photothermal activation results in increased release within few minutes, with release rates tunable through power density of the applied irradiation. The large difference over passive and active release, as well as the controlled turn-on of release allow regulation of the dosage of the antibiotics, as evidenced by the inhibition of planktonic bacteria growth. Treatment of superficial skin infections with the antibiotic-loaded nanofiber mats shows efficient wound healing of the infected site. Facile fabrication and implementation of these photothermally active nanofiber mats makes this novel platform adaptable for on-demand delivery of various therapeutic agents.

Drug Delivery Systems from Self-Assembly of Dendron-Polymer Conjugates †.

This review highlights the utilization of dendron-polymer conjugates as building blocks for the fabrication of nanosized drug delivery vehicles. The examples given provide an overview of the evolution of these delivery platforms, from simple micellar containers to smart stimuli- responsive drug delivery systems through their design at the macromolecular level. Variations in chemical composition and connectivity of the dendritic and polymeric segments provide a variety of self-assembled micellar nanostructures that embody desirable attributes of viable drug delivery systems.