Hybrid Shear-Thinning Hydrogel Integrating Hyaluronic Acid with ROS-Responsive Nanoparticles

Nanoparticle (NP) supra-assembly offers unique opportunities to tune macroscopic hydrogels’ mechanical strength, material degradation, and drug delivery properties. Here, synthetic, reactive oxygen species (ROS)-responsive NPs are physically cross-linked with hyaluronic acid (HA) through guest-host chemistry to create shear-thinning NP/HA hydrogels. A library of triblock copolymers composed of poly(propylene sulfide)-b-poly(N,N-dimethylacrylamide)-b-poly(N,N-dimethylacrylamide-co-N-(1-adamantyl)acrylamide) are synthesized with varied triblock architectures and adamantane grafting densities and then self-assembled into NPs displaying adamantane on their surface. Self-assembled NPs are mixed with β-cyclodextrin grafted HA to yield eighteen NP/HA hydrogel formulations. The NP/HA hydrogel platform demonstrates superior mechanical strength to HA-only hydrogels, susceptibility to oxidative/enzymatic degradation, and inherent cell-protective, antioxidant function. The performance of NP/HA hydrogels is shown to be affected by triblock architecture, guest/host grafting densities, and HA composition. In particular, the length of the hydrophilic second block and adamantane grafting density of self-assembled NPs significantly impacts hydrogel mechanical properties and shear-thinning behavior, while ROS-reactivity of poly(propylene sulfide) protects cells from cytotoxic ROS and reduces oxidative degradation of HA compared to HA-only hydrogels. This study provides insight into polymer structure-function considerations for designing hybrid NP/HA hydrogels and identifies antioxidant, shear-thinning hydrogels as promising injectable delivery platforms for small molecule drugs and therapeutic cells.     

Poly(N‐isopropylacrylamide)‐Clay Nanocomposite Hydrogels with Responsive Bending Property as Temperature‐Controlled Manipulators

Novel poly(N‐isopropylacrylamide)‐clay (PNIPAM‐clay) nanocomposite (NC) hydrogels with both excellent responsive bending and elastic properties are developed as temperature‐controlled manipulators. The PNIPAM‐clay NC structure provides the hydrogel with excellent mechanical property, and the thermoresponsive bending property of the PNIPAM‐clay NC hydrogel is achieved by designing an asymmetrical distribution of nanoclays across the hydrogel thickness. The hydrogel is simply fabricated by a two‐step photo polymerization. The thermoresponsive bending property of the PNIPAM‐clay NC hydrogel is resulted from the unequal forces generated by the thermoinduced asynchronous shrinkage of hydrogel layers with different clay contents. The thermoresponsive bending direction and degree of the PNIPAM‐clay NC hydrogel can be adjusted by controlling the thickness ratio of the hydrogel layers with different clay contents. The prepared PNIPAM‐clay NC hydrogels exhibit rapid, reversible, and repeatable thermoresponsive bending/unbending characteristics upon heating and cooling. The proposed PNIPAM‐clay NC hydrogels with excellent responsive bending property are demonstrated as temperature‐controlled manipulators for various applications including encapsulation, capture, and transportation of targeted objects. They are highly attractive material candidates for stimuli‐responsive “smart” soft robots in myriad fields such as manipulators, grippers, and cantilever sensors.     

A pH‐Responsive Gating Membrane System with Pumping Effects for Improved Controlled Release

In this study, we report on a novel composite membrane system for pH‐responsive controlled release, which is composed of a porous membrane with linear grafted, positively pH‐responsive polymeric gates acting as functional valves, and a crosslinked, negatively pH‐responsive hydrogel inside the reservoir working as a functional pumping element. The proposed system features a large responsive release rate that goes effectively beyond the limit of concentration‐driven diffusion due to the pumping effects of the negatively pH‐responsive hydrogel inside the reservoir. The pH‐responsive gating membranes were prepared by grafting poly(methacrylic acid) (PMAA) linear chains onto porous polyvinylidene fluoride (PVDF) membrane substrates using a plasma‐graft pore‐filling polymerization, and the crosslinked poly(N,N‐dimethylaminoethyl methacrylate) (PDM) hydrogels were synthesized by free radical polymerization. The volume phase‐transition characteristics of PMAA and PDM were opposite. The proposed system opens new doors for pH‐responsive “smart” or “intelligent” controlled‐release systems, which are highly attractive for drug‐delivery systems, chemical carriers, sensors, and so on.     

Nanostructured Poly(styrene‐b‐butadiene‐b‐styrene) (SBS) Membranes for the Separation of Nitrogen from Natural Gas

The preparation and characterization of new, tailor‐made polymeric membranes using poly(styrene‐b‐butadiene‐b‐styrene) (SBS) triblock copolymers for gas separation are reported. Structural differences in the copolymer membranes, obtained by manipulation of the self‐assembly of the block copolymers in solution, are characterized using atomic force microscopy, transmission electron microscopy, and the transport properties of three gases (CO₂, N₂, and CH₄). The CH₄/N₂ ideal selectivity of 7.2, the highest value ever reported for block copolymers, with CH₄ permeability of 41 Barrer, is obtained with a membrane containing the higher amount of polybutadiene (79 wt%) and characterized by a hexagonal array of columnar polystyrene cylinders normal to the membrane surface. Membranes with such a high separation factor are able to ease the exploitation of natural gas with high N₂ content. The CO₂/N₂ ideal selectivity of 50, coupled with a CO₂ permeability of 289 Barrer, makes SBS a good candidate for the preparation of membranes for the post‐combustion capture of carbon dioxide.     

Positively K+‐Responsive Membranes with Functional Gates Driven by Host–Guest Molecular Recognition

A novel positively K⁺‐responsive membrane with functional gates driven by host‐guest molecular recognition is prepared by grafting poly(N‐isopropylacrylamide‐co‐acryloylamidobenzo‐15‐crown‐5) (poly(NIPAM‐co‐AAB₁₅C₅)) copolymer chains in the pores of porous nylon‐6 membranes with a two‐step method combining plasma‐induced pore‐filling grafting polymerization and chemical modification. Due to the cooperative interaction of host‐guest complexation and phase transition of the poly(NIPAM‐co‐AAB₁₅C₅), the grafted gates in the membrane pores could spontaneously switch from “closed” state to “open” state by recognizing K⁺ ions in the environment and vice versa; while other ions (e.g., Na⁺, Ca²⁺ or Mg²⁺) can not trigger such an ion‐responsive switching function. The positively K⁺‐responsive gating action of the membrane is rapid, reversible, and reproducible. The proposed K⁺‐responsive gating membrane provide a new mode of behavior for ion‐recognizable “smart” or “intelligent” membrane actuators, which is highly attractive for controlled release, chemical/biomedical separations, tissue engineering, sensors, etc.     

Multifunctional Up‐Converting Nanocomposites with Smart Polymer Brushes Gated Mesopores for Cell Imaging and Thermo/pH Dual‐Responsive Drug Controlled Release

Multifunctional nanocarriers based on the up‐conversion luminescent nanoparticles of NaYF₄:Yb³⁺/Er³⁺ core (UCNPs) and thermo/pH‐coupling sensitive polymer poly[(N‐isopropylacrylamide)‐co‐(methacrylic acid)] (P(NIPAm‐co‐MAA)) gated mesoporous silica shell are reported for cancer theranostics, including fluorescence imaging, and for controlled drug release for therapy. The as‐synthesized hybrid nanospheres UCNPs@mSiO₂‐P(NIPAm‐co‐MAA) show bright green up‐conversion fluorescence under 980 nm laser excitation and the thermo/pH‐sensitive polymer is active as a “valve” to moderate the diffusion of the embedded drugs in‐and‐out of the pore channels of the silica container. The anticancer drug doxorubicin hydrochloride (DOX) can be absorbed into UCNPs@mSiO₂‐P(NIPAm‐co‐MAA) nanospheres and the composite drug delivery system (DDS) shows a low level of leakage at low temperature/high pH values but significantly enhanced release at higher temperature/lower pH values, exhibiting an apparent thermo/pH controlled “on‐off” drug release pattern. The as‐prepared UCNPs@mSiO₂‐P(NIPAm‐co‐MAA) hybrid nanospheres can be used as bioimaging agents and biomonitors to track the extent of drug release. The reported multifunctional nanocarriers represent a novel and versatile class of platform for simultaneous imaging and stimuli‐responsive controlled drug delivery.     

Conductive “Smart” Hybrid Hydrogels with PNIPAM and Nanostructured Conductive Polymers

Stimuli‐responsive hydrogels with decent electrical properties are a promising class of polymeric materials for a range of technological applications, such as electrical, electrochemical, and biomedical devices. In this paper, thermally responsive and conductive hybrid hydrogels are synthesized by in situ formation of continuous network of conductive polymer hydrogels crosslinked by phytic acid in poly(N‐isopropylacrylamide) matrix. The interpenetrating binary network structure provides the hybrid hydrogels with continuous transporting path for electrons, highly porous microstructure, strong interactions between two hydrogel networks, thus endowing the hybrid hydrogels with a unique combination of high electrical conductivity (up to 0.8 S m^?1), high thermoresponsive sensitivity (significant volume change within several seconds), and greatly enhanced mechanical properties. This work demonstrates that the architecture of the filling phase in the hydrogel matrix and design of hybrid hydrogel structure play an important role in determining the performance of the resulting hybrid material. The attractive performance of these hybrid hydrogels is further demonstrated by the developed switcher device which suggests potential applications in stimuli‐responsive electronic devices.     

Confinement of Thermoresponsive Hydrogels in Nanostructured Porous Silicon Dioxide Templates

A thermoresponsive hydrogel, poly(N‐isopropylacrylamide) (poly(NIPAM)), is synthesized in situ within an oxidized porous Si template, and the nanocomposite material is characterized. Infiltration of the hydrogel into the interconnecting nanoscale pores of the porous SiO₂ host is confirmed by scanning electron microscopy. The optical reflectivity spectrum of the nanocomposite hybrid displays Fabry–Pérot fringes characteristic of thin film interference, enabling direct, real‐time observation of the volume phase transition of the confined poly(NIPAM) hydrogel. Reversible optical reflectivity changes are observed to correlate with the temperature‐dependent volume phase transition of the hydrogel, providing a new means of studying nanoscale confinement of responsive hydrogels. The confined hydrogel displays a swelling and shrinking response to changes in temperature that is significantly faster than that of the bulk hydrogel. The porosity and pore size of the SiO₂ template, which are precisely controlled by the electrochemical synthesis parameters, strongly influence the extent and rate of changes in the reflectivity spectrum of the nanocomposite. The observed optical response is ascribed to changes in both the mechanical and the dielectric properties of the nanocomposite.     

An Injectable Supramolecular Polymer Nanocomposite Hydrogel for Prevention of Breast Cancer Recurrence with Theranostic and Mammoplastic Functions

The high locoregional breast cancer recurrence rate poses a significant risk for patients' survival. Injecting theranostic drugs‐laden soft tissue‐like hydrogels into the resected breast cavity is a promising strategy to achieve both precisely local therapy of breast cancer and reconstructive mammoplasty. In this work, a robust injectable thermoresponsive supramolecular poly(N‐acryloyl glycinamide‐co‐acrylamide) (PNAm) hydrogel bearing polydopamine (PDA) coated‐gold nanoparticles (AuNPs) and doxorubicin (DOX) is fabricated. The supramolecular polymer nanocomposite (SPN) hydrogels exhibit an excellent photothermal effect arising from PDA‐AuNPs that are tightly fixed to the hydrogel matrix via PDA and amide moieties in the network, built‐in near infrared (NIR) light‐triggered gel–sol transition as well as tunable drug delivery. The PNAm‐PDAAu‐DOX sol driven by prior heating is injected into the cavity of resected cancerous breasts of rats where gelation occurred rapidly while the temperature decreased to body temperature, thereby finely serving as a breast filler. During 4 week of implantation, interval NIR light irradiation can mediate photothermal effect and concertedly controllable DOX release, thus collectively preventing the recurrence of breast cancer. Remarkably, this stable remoldable SPN hydrogel facilitates the breast reconstruction and can be tracked by computed tomography (CT) imaging owing to the intrinsic X‐ray attenuation property of the loaded AuNPs.     

Stepwise Drug‐Release Behavior of Onion‐Like Vesicles Generated from Emulsification‐Induced Assembly of Semicrystalline Polymer Amphiphiles

Tailoring unique nanostructures of biocompatible and degradable polymers and the consequent elucidation of shape effects in drug delivery open tremendous opportunities not only to broaden their biomedical applications but also to identify new directions for the design of nanomedicine. Cellular organelles provide the basic structural and functional motif for the development of novel artificial nanoplatforms. Herein, aqueous onion‐like vesicles structurally mimicking multicompartmentalized cellular organelles by exhibiting exquisite control over the molecular assembly of poly(ethylene oxide)‐block‐poly(ε‐caprolactone) (PEO‐b‐PCL) semicrystalline amphiphiles are reported. Compared to in situ self‐assembly, emulsification‐induced assembly endows the resulting nanoaggregates of PEO‐b‐PCL with structural diversity such as helical ribbons and onion‐like vesicles through the molecular packing modification in the hydrophobic core with a reduction of inherent crystalline character of PCL. In particular, onion‐like vesicles composed of alternating walls and water channels are interpreted by nanometer‐scale 3D visualization via cryogenic‐electron tomo­graphy (cryo‐ET). Interestingly, the nature of the multi‐walled vesicles results in high drug‐loading capacity and stepwise drug release through hydrolytic cleavage of the PCL block. The crystalline arrangement of PCL at the molecular scale and the spatial organization of assembled structure at the nanoscale significantly affect the drug‐release behavior of PEO‐b‐PCL nanovehicles.     

Biocompatible Poly(2‐hydroxyethyl methacrylate)‐b‐poly(L‐histidine) Hybrid Materials for pH‐Sensitive Intracellular Anticancer Drug Delivery

A series of synthetic polymer bioconjugate hybrid materials consisting of poly(2‐hydroxyethyl methacrylate) (p(HEMA)) and poly(l‐ histidine) (p(His)) are synthesized by combining atom transfer radical polymerization of HEMA with ring opening polymerization of benzyl‐N‐carboxy‐L ‐histidine anhydride. The resulting biocompatible and membranolytic p(HEMA)₂₅‐b‐p(His)_n (n = 15, 25, 35, and 45) polymers are investigated for their use as pH‐sensitive drug‐carrier for tumor targeting. Doxorubicin (Dox) is encapsulated in nanosized micelles fabricated by a self‐assembly process and delivered under different pH conditions. Micelle size is characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM) observations. Dox release is investigated according to pH, demonstrating the release is sensitive to pH. Antitumor activity of the released Dox is assessed using the HCT 116 human colon carcinoma cell line. Dox released from the p(HEMA)‐b‐p(His) micelles remains biologically active and has the dose‐dependent capability to kill cancer cells at acidic pH. The p(HEMA)‐b‐p(His) hybrid materials are capable of self‐assembling into nanomicelles and effectively encapsulating the chemotherapeutic agent Dox, which allows them to serve as suitable carriers of drug molecules for tumor targeting.     

pH‐Responsive Flower‐Type Micelles Formed by a Biotinylated Poly(2‐vinylpyridine)‐block‐poly(ethylene oxide)‐block‐poly(ε‐caprolactone) Triblock Copolymer

In the present work, a method is proposed to assemble pH‐responsive, flower‐like micelles that can expose a targeting unit at their periphery upon a decrease in pH. The micelles are composed of a novel biotinylated triblock copolymer of poly(εε‐caprolactone)‐block‐poly(ethylene oxide)‐block‐poly(2‐vinylpyridine) (PCL‐b‐PEO‐b‐P2VP) and the non‐biotinylated analogue. The block copolymers are synthesized by sequential anionic and ring‐opening polymerization. The pH‐dependent micellization behaviour in aqueous solution of the triblock copolymers developed is studied using dynamic light scattering, zeta potential, transmission electron microscopy (TEM), and fluorimetric measurements. The shielding of the biotin at neutral pH and their availability at the micelle surface upon protonation is established by TEM and surface plasmon resonance with avidin and streptavidin‐coated gold surfaces. The preliminary stealthy behavior of these pH‐responsive micelles is examined using the complement activation (CH50) test.     

Photothermally Sensitive Poly(N‐isopropylacrylamide)/Graphene Oxide Nanocomposite Hydrogels as Remote Light‐Controlled Liquid Microvalves

A photothermally sensitive poly(N‐isopropylacrylamide)/graphene oxide (PNIPAM/GO) nanocomposite hydrogel can be synthesized by in situ γ‐irradiation‐assisted polymerization of an aqueous solution of N‐isopropylacrylamide monomer in the presence of graphene oxide (GO). The colors and phase‐transition temperatures of the PNIPAM/GO hydrogels change with different GO doping levels. Due to the high optical absorbance of the GO, the nanocomposite hydrogel shows excellent photothermal properties, where its phase transitions can be controlled remotely by near‐infrared (NIR) laser irradiation, and it is completely reversible via laser exposure or non‐exposure. With a higher GO loading, the NIR‐induced temperature of the nanocomposite hydrogel increases more quickly than with a lower doping level and the temperature can be tuned effectively by the irradiation time. The nanocomposite hydrogel with its excellent photothermal properties will have great applications in the biomedical field, especially as microfluidic devices; this has been demonstrated in our experiments by way of remote microvalves to control fluidic flow. Such an “easy” and “clean” synthetic procedure initiated by γ‐irradiation can be extended for the efficient synthesis of other nanocomposite materials.     

Color Tunable Poly (N‐Isopropylacrylamide)‐co‐Acrylic Acid Microgel–Au Hybrid Assemblies

A new class of materials that are capable of color tunability over 300 nm with a 15 °C temperature change is introduced. The materials are assembled from thermoresponsive poly (N‐isopropylacrylamide)‐co‐acrylic acid (pNIPAm‐co‐AAc) microgels, which are deposited on Au coated glass substrates. The films are also pH responsive; the temperature‐induced color change was suppressed at high pH and is consistent with the behavior of a solution of suspended microgels. The mechanism proposed to account for the observed optical properties suggests that they result from the two Au layers being separated from each other by the “monolithic” microgel film, much like a Fabry‐Pérot etalon or interferometer. It is the modulation of the distance between these two layers, facilitated by the microgel collapse transition at high temperature, that allows the color to be tuned. The sensitivity of the system presented here will be used for future sensing and biosensing applications, as well as for light filtering applications.     

Microphase‐Separated Donor–Acceptor Diblock Copolymers: Influence of HOMO Energy Levels and Morphology on Polymer Solar Cells

The synthesis of novel semiconducting donor–acceptor (D–A) diblock copolymers by means of nitroxide‐mediated polymerization (NMP) is reported. The copolymers contain functional moieties for hole transport, electron transport, and light absorption. The first block, representing the donor, is made up of either substituted triphenylamines (poly(bis(4‐methoxyphenyl)‐4′‐vinylphenylamine), PvDMTPA) or substituted tetraphenylbenzidines (poly(N,N′‐bis(4‐methoxyphenyl)‐N‐phenyl‐N′‐4‐vinylphenyl‐(1,1′‐biphenyl)‐4,4′‐diamine), PvDMTPD). The second block consists of perylene diimide side groups attached to a polyacrylate backbone (PPerAcr) via a flexible spacer. This block is responsible for absorption in the visible range and for electron‐transport properties. The electrochemical properties of these fully functionalized diblock copolymers, PvDMTPA‐b‐PPerAcr and PvDMTPD‐b‐PPerAcr, are investigated by cyclic voltammetry (CV), and their morphology is investigated by transmission electron microscopy (TEM). All diblock copolymers exhibit microphase‐separated domains in the form of either wire‐ or wormlike structures made of perylene diimide embedded in a hole‐conductor matrix. In single‐active‐layer organic solar cells, PvDMTPD‐b‐PPerAcr reveals a fourfold improvement in power conversion efficiency (η = 0.26 %, short‐circuit current (I_SC) 1.21 mA cm^–2), and PvDMTPA‐b‐PPerAcr a fivefold increased efficiency (η = 0.32 %, I_SC = 1.14 mA cm^–2) compared with its unsubstituted analogue PvTPA‐b‐PPerAcr (η = 0.065 %, I_SC = 0.23 mA cm^–2).     

Programmed Deformations of 3D‐Printed Tough Physical Hydrogels with High Response Speed and Large Output Force

Shape‐morphing hydrogels have emerging applications in biomedical devices, soft robotics, and so on. However, successful applications require a combination of excellent mechanical properties and fast responding speed, which are usually a trade‐off in hydrogel‐based devices. Here, a facile approach to fabricate 3D gel constructs by extrusion‐based printing of tough physical hydrogels, which show programmable deformations with high response speed and large output force, is described. Highly viscoelastic poly(acrylic acid‐co‐acrylamide) (P(AAc‐co‐AAm)) and poly(acrylic acid‐co‐N‐isopropyl acrylamide) (P(AAc‐co‐NIPAm)) solutions or their mixtures are printed into 3D constructs by using multiple nozzles, which are then transferred into FeCl₃ solution to gel the structures by forming robust carboxyl–Fe³⁺ coordination complexes. The printed gel fibers containing poly(N‐isopropyl acrylamide) segment exhibit considerable volume contraction in concentrated saline solution, whereas the P(AAc‐co‐AAm) ones do not contract. The mismatch in responsiveness of the gel fibers affords the integrated 3D gel constructs the shape‐morphing ability. Because of the small diameter of gel fibers, the printed gel structures deform and recover with a fast speed. A four‐armed gripper is designed to clamp plastic balls with considerable holding force, as large as 115 times the weight of the gripper. This strategy should be applicable to other tough hydrogels and broaden their applications.     

Self‐Assembly of a Micelle Structure from Graft and Diblock Copolymers: An Example of Overcoming the Limitations of Polyions in Drug Delivery

A novel mixed micelle with a multifunctional core and shell is successfully prepared from a graft copolymer, poly(N‐isopropyl acrylamide‐co‐methacrylic acid)‐g‐poly(d,l ‐lactide) (P(NIPAAm‐co‐MAAc)‐g‐PLA) and two diblock copolymers, poly(ethylene glycol)‐b‐poly(d,l ‐lactide) and poly (2‐ethyl‐2‐oxazoline)‐b‐poly(d,l ‐lactide). This nanostructure completely screens the highly negative charges of the graft copolymer and exhibits multifunctionality because it has a specialized core/shell structure. An example of this micelle structure used in intracellular drug delivery demonstrates a strong relationship between drug release and the functionality of the mixed micelle. Additionally, the efficiency of the screening feature is also displayed in the cytotoxicities; mixed micelles exhibit higher drug activity and lower material cytotoxicity than micelles from P(NIPAAm‐co‐MAAc)‐g‐PLA ([NIPAAm]/[MAAc]/[PLA] = 84:5.9:2.5 mol/mol) copolymer. This study not only presents a new micelle structure generated using a graft–diblock copolymer system, but also elucidates concepts upon which the preparation of a multifunctional micelle from a graft copolymer with a single (or many) diblock copolymer(s) can be based for applications in drug delivery.     

An Intelligent Transdermal Formulation of ALA-Loaded Copolymer Thermogel with Spontaneous Asymmetry by Using Temperature-Induced Sol–Gel Transition and Gel–Sol (Suspension) Transition on Different Sides

Aqueous solutions of some amphiphilic block copolymers undergo a sol–gel transition upon heating and are thus called thermogels. In the thermogel family, some systems also exhibit a gel–sol (suspension) transition at higher temperatures following the sol–gel transition, which is usually ignored in biomedical applications. Herein, for the first time, a case is reported employing both the sol–gel transition and the gel–sol (suspension) transition, which is found in the development of a transdermal hydrogel formulation containing 5-aminolevulinic acid for photodynamic therapy (PDT) of skin disease. Two poly(d ,l -lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d ,l -lactide-co-glycolide) triblock copolymers of different block lengths are synthesized. The transition temperatures of the formulation can be easily adjusted to meet the condition of sol–gel transition temperature (T_gel) < room temperature (T_air) < gel–sol (suspension) temperature (T_{sol (suspension)}) < body temperature (T_body) via changing the blending ratio. Therefore, after applying to skin, formulation of spontaneous asymmetry with a hydrogel outside and a sol (suspension) inside can avoid free flowing and achieve rapid release to ensure an efficient PDT. This study demonstrates such a concept via characterizations of the “block blend” biomaterials and drug release profiles, and also via cell experiments, in vitro permeation, and in vivo transdermal delivery studies.     

A Thermoresponsive Antimicrobial Wound Dressing Hydrogel Based on a Cationic Betaine Ester

This work reports a thermoresponsive multifunctional wound dressing hydrogel based on ABA triblock copolymers synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization. The inner B block consists of a positively‐charged hydrolysable betaine ester loaded with an antimicrobial drug as its counter ion and the B block is flanked by two outer A blocks of thermoresponsive poly (N‐isopropylacrylamide) (PNIPAM). A solution containing the triblock copolymers can be applied to wound sites and immediately turns into a physical gel at the body temperature. This wound dressing can reduce the risk of wound infection by releasing small‐molecular‐weight antimicrobial drug and facilitate the attachment of mammalian cells during tissue regeneration through its positive surface charge. The cationic betaine ester can then hydrolyze at the wound site to its zwitterionic form, which is known to be biocompatible and nonsticky. The thermoresponsive in situ gelation feature along with controlled drug release, enhanced tissue–hydrogel interactions as well as long‐term biocompatibility make this hydrogel a very promising material for antimicrobial wound dressing applications.     

Multifunctional Micelles for Cancer Cell Targeting,Distribution Imaging,and Anticancer Drug Delivery

Multifunctional micelles for cancer cell targeting, distribution imaging, and anticancer drug delivery were prepared from an environmentally‐sensitive graft copolymer, poly(N‐isopropyl acrylamide‐co‐methacryl acid)‐g‐poly(D ,L ‐lactide) (P(NIPAAm‐co‐MAAc)‐g‐PLA), a diblock copolymer, methoxy poly(ethylene glycol)‐b‐poly(D ,L ‐lactide) (mPEG‐PLA) and two functionalized diblock copolymers, galactosamine‐PEG‐PLA (Gal‐PEG‐PLA) and fluorescein isothiocyanate‐PEG‐PLA (FITC‐PEG‐PLA). Anticancer drug, free base doxorubicin (Dox) was incorporated into the inner core of multifunctional micelles by dialysis. From the drug release study, a change in pH (from pH 7.4 to 5.0) deformed the structure of the inner core from that of aggregated P(NIPAAm‐co‐MAAc), causing the release of a significant quantity of doxorubicin (Dox) from multifunctional micelles. Multifunctional micelles target specific tumors by an asialoglycoprotein (HepG2 cells)‐Gal (multifunctional micelle) receptor‐mediated tumor targeting mechanism. This mechanism then causes intracellular pH changes which induce Dox release from multifunctional micelles and that micelles have strong effects on the viability of HepG2 cells and are abolished by galactose. Confocal laser scanning microscopy (CLSM) reveals a clear distribution of multifunctional micelles. With careful design and sophisticated manipulation, polymeric micelles can be widely used in cancer diagnosis, cancer targeting, and cancer therapy simultaneously.