Stretchable, Environment-Stable, and Knittable Ionic Conducting Fibers Based on Metallogels for Wearable Wide-Range and Durable Strain Sensors.

The construction of fibrous ionic conductors and sensors with large stretchability, low-temperature tolerance, and environmental stability is highly desired for practical wearable devices yet is challenging. Herein, metallogels (MOGs) with a rapidly reversible force-stimulated sol-gel transition were employed and encapsulated into a hollow thermoplastic elastomer (TPE) microfiber through a simple coaxial spinning. The resultant MOG@TPE coaxial fiber exhibited a high stretchability (>100%) in a broad temperature range (-50 to 50 °C). The MOG@TPE fibrous strain sensor demonstrated a high-yet-linear working curve, fast response time (<100 ms), highly stable conductivity under large deformation, and excellent cycling stability (>3000 cycles). The MOG@TPE fibrous sensors were demonstrated to be directly attached to the human skin to monitor the real-time movements of large/facet joints of the elbow, wrist, finger, and knee. It is believed that the present work for preparing the stretchable ionic conductive fibers holds great promise for applications in fibrous wearable sensors with broad temperature range, large stretchability, stable conductivity, and high wearing comfort.

Dual Tumor Microenvironment Remodeling by Glucose-Contained Radical Copolymer for MRI-Guided Photoimmunotherapy.

Aberrant glucose metabolism and immune evasion are recognized as two hallmarks of cancer, which contribute to poor treatment efficiency and tumor progression. Herein, a novel material system consisting of a glucose and TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl) at the distal ends of PEO-b-PLLA block copolymer (glucose-PEO-b-PLLA-TEMPO), is designed to encapsulate clinical therapeutics CUDC101 and photosensitizer IR780. The specific core-shell rod structure formed by the designed copolymer renders TEMPO radicals excellent stability against reduction-induced magnetic resonance imaging (MRI) silence. Tumor-targeting moiety endowed by glucose provides the radical copolymer outstanding multimodal imaging capabilities, including MRI, photoacoustic imaging, and fluorescence imaging. Efficient delivery of CUDC101 and IR780 is achieved to synergize the antitumor immune activation through IR780-mediated photodynamic therapy (PDT) and CUDC101-triggered CD47 inhibition, showing M1 phenotype polarization of tumor-associated macrophages (TAMs). More intriguingly, this study demonstrates PDT-stimulated p53 can also re-educate TAMs, providing a combined strategy of using dual tumor microenvironment remodeling to achieve the synergistic effect in the transition from cold immunosuppressive to hot immunoresponsive tumor microenvironment.

Template-free construction of hollow mesoporous carbon spheres from a covalent triazine framework for enhanced oxygen electroreduction.

The construction of hollow mesoporous carbon nanospheres (HMCS) avoiding the use of traditional soft/hard templates is highly desired for nanoscience yet challenging. Herein, we report a simple and straightforward template-free strategy for preparing nitrogen, sulfur dual-doped HMCSs (N/S-HMCSs) as oxygen reduction reaction (ORR) electrocatalysts. The unique hollow spherical and mesoporous structure was in-situ formed via a thermally initiated hollowing pathway from an elaborately engineered covalent triazine framework. Regulation of pyrolysis temperatures contributed to precisely tailoring of the shell thickness of HMCSs. The resulting N/S-HMCS900 (pyrolyzed at 900 °C) possessed high N and S contents, large specific surface areas, rich and uniform mesopores distribution. Consequently, as a metal-free ORR electrocatalyst, N/S-HMCS900 exhibits a high half-wave potential, excellent methanol tolerance and great long-term durability. Additionally, density functional theory calculations demonstrate that N, S-dual dopant can create extra active sites with higher catalytic activity than the isolated N-dopant. This strategy provides new insights into the construction of hollow and mesoporous multi-heteroatom-doped carbon materials with tunable nanoarchitecture for various electrochemical applications.

Self-organization of unimolecular micelles in beam stream for functional mesoporous metal oxide nanofibers.

The use of linear amphiphilic block copolymers as templates is an important method for the preparation of mesoporous materials. However, the obtained assemblies are usually sensitive to synthetic conditions, which impedes the preparation of such mesoporous materials in certain environments. Herein, we report a universal strategy applying an amphiphilic multi-arm triblock copolymer in the preparation of mesoporous metal oxide nanofibers (NFs) using one metal oxide (TiO2, ZrO2, WO3, CeO2), or two (TiO2/WO3, TiO2/ZrO2, TiO2/CeO2) and three (TiO2/WO3/CuO) metal oxides as composites. The template consists of modified ß-cyclodextrin as the center of the macromolecule which is attached sequentially to a block of polystyrene, poly(acrylic acid), and poly(ethylene oxide). Under electrospinning conditions, stable unimolecular micelles are formed and effectively co-assemble with metal ions to form fibrous nanostructures. As indicated by various characterization methods, the synthesized TiO2 and its derived composite NFs maintain a straight and continuous fibrous structure after calcination, and TiO2 NFs exhibit uniform mesopores of 10.8 nm in diameter and a large Brunauer-Emmett-Teller surface area of 143.3 m2 g-1. Benefiting from the characteristic structure, still present after modification, Pt-decorated mesoporous TiO2 NFs display excellent ability in the visible-light photocatalytic degradation of tetracycline, which is superior to the commercial P25 catalyst. This study reveals a promising strategy for the preparation of fibrous mesoporous metal oxides.

Ultrastretchable and Stable Conductive Elastomer Based on Micro-Ionicgel for Wide-Working-Range Sensors.

A facile route to novel stretchable conductive elastomers with micro-ionicgel acting as conductive fillers was developed via oil-in-oil Pickering emulsion polymerization of nonpolar monomers A and a mixture of polar monomers B and ionic liquids (ILs). Oil-in-oil Pickering emulsions were first fabricated by mixing n-butyl acrylate (n-BA), acrylic acid (AA), ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate, [EMIM]+[BF4]-), and alkyl vinyl-functionalized silica particles. The emulsion structure was directly observed using the dye-labeled AA-IL phase by confocal fluorescence microscopy. Upon polymerization, the IL-based conductive composite elastomers were obtained, where the continuous phase and the dispersed phase are poly(n-butyl acrylate) (PnBA) and poly(acrylic acid) containing ILs (PAA-ILs, referred to as micro-ionicgel), respectively. The PnBA matrix endows the formed elastomer with extremely large stretchability (up to 12 000% strain) and insensitivity to moisture. The micro-ionicgels PAA-ILs not only contribute to good conductivity but can also prevent the leakage of ILs upon stretching or folding. The electrical impedance-based stretchable sensors fabricated using this IL elastomer could detect various human motions including the bending of a finger, wrist, elbow, and knee. Therefore, the as-developed sensors show promising applications for human-machine interfaces of flexible wearable sensors.

Enhanced drug retention by anthracene crosslinked nanocomposites for bimodal imaging-guided phototherapy.

Efficient drug delivery, multifunctional combined therapy and real-time diagnosis are the main hallmarks in the exploitation of precision nanomedicine. Herein, an anthracene-functionalized micelle containing a magnetic resonance imaging (MRI) contrast agent, upconversion nanoparticles (UCNPs) and the photosensitizer IR780 is designed to achieve sustained drug release and enhanced photothermal and photodynamic therapy. The polymer-coated hybrid micelle was achieved by crosslinking anthracene-dimer with UV light (λ > 300 nm), which is converted from near-infrared (NIR) irradiation upon UCNPs. Besides, the water-insoluble photosensitizer IR780 is introduced into the system to achieve efficient drug delivery and photothermal and photodynamic synergistic therapy. As a consequence of NIR-induced anthracene-dimer formation, the cross-linked nanocomposite shows sustained drug release, and the enhanced retention effect of IR780 could increase the photothermal conversion efficiency. Importantly, the incorporation of 2,2,6,6-tetramethyl-piperidineoxyl (TEMPO) as a nitroxide MRI contrast agent presents the potential for real-time diagnosis via nanotheranostics, and the fluorescence imaging of IR780 is applied to monitor drug distribution and metabolism. This strategy of sustained drug delivery by anthracene-dimer formation through the better penetration depth of NIR-II fluorescence provides an executable platform to achieve enhanced phototherapy in biomedical applications.

AuNPs Decorated PLA Stereocomplex Micelles for Synergetic Photothermal and Chemotherapy.

A unique platform for combined photothermal and chemotherapy using PLA stereocomplex (PLA SC) micelles-induced hybrid gold nanocarriers is designed. The PLA SC micelles, made from the self-assembly of poly(ethylene glycol)-block-poly(l-lactide) (PEG-PLLA) and poly(2-(dimethylamino) ethyl methacrylate)-block-poly(d-lactide) (PDMAEMA-PDLA), for the first time are used as a template to fabricate the hybrid PLA SC@Au core-shell nanocarriers, in which the anticancer drugs are encapsulated within the core, while the Au nanoparticles are tethered in the shell via the in situ reduction of AuCl4- by PDMAEMA. The obtained PLA SC@Au hybrid nanocarriers exhibit low toxicity and remarkable photothermal effect. Upon near-infrared laser irradiation, the on-site photothermal therapy can further induce an accelerated drug release from the hybrid nanocarrier reservoir via hyperthermia heating of the nanocarriers, thus leading to a synergistic photothermal and chemotherapy toward a significantly improved efficacy in tumor shrinkage. The as-designed PLA SC@Au hybrid nanocarriers, with their biocompatible compositions, dual-drug delivery characteristics, and combined photothermal/chemotherapy, show high potential as a novel platform for cancer treatment.

Cyclodextrin-Based Hybrid Polymeric Complex to Overcome Dual Drug Resistance Mechanisms for Cancer Therapy.

Drug resistance always reduces the efficacy of chemotherapy, and the classical mechanisms of drug resistance include drug pump efflux and anti-apoptosis mediators-mediated non-pump resistance. In addition, the amphiphilic polymeric micelles with good biocompatibility and high stability have been proven to deliver the drug molecules inside the cavity into the cell membrane regardless of the efflux of the cell membrane pump. We designed a cyclodextrin (CD)-based polymeric complex to deliver chemotherapeutic doxorubicin (DOX) and Nur77ΔDBD gene for combating pumps and non-pump resistance simultaneously. The natural cavity structure of the polymeric complex, which was comprised with ß-cyclodextrin-graft-(poly(ε-caprolactone)-adamantly (ß-CD-PCL-AD) and ß-cyclodextrin-graft-(poly(ε-caprolactone)-poly(2-(dimethylamino) ethyl methacrylate) (ß-CD-PCL-PDMAEMA), can achieve the efficient drug loading and delivery to overcome pump drug resistance. The excellent Nur77ΔDBD gene delivery can reverse Bcl-2 from the tumor protector to killer for inhibiting non-pump resistance. The presence of terminal adamantyl (AD) could insert into the cavity of ß-CD-PCL-PDMAEMA via host-guest interaction, and the releasing rate of polymeric inclusion complex was higher than that of the individual ß-CD-PCL-PDMAEMA. The polymeric inclusion complex can efficiently deliver the Nur77ΔDBD gene than polyethylenimine (PEI-25k), which is a golden standard for nonviral vector gene delivery. The higher transfection efficacy, rapid DOX cellular uptake, and significant synergetic tumor cell viability inhibition were achieved in a pump and non-pump drug resistance cell model. The combined strategy with dual drug resistance mechanisms holds great potential to combat drug-resistant cancer.

A review on the methods of determining ecological thresholds.

The drastic changes or threshold phenomena of ecosystems in response to environmental changes are main research focuses in ecology. However, the difficulty in quantitative detection of ecological thresholds hinders the further research progress and application of this topic. Based on typical cases, we analzyed the driving-response mechanism of S-shaped curve type, subsidy-stress type, step type of the potential ecological thresholds. Seven methods to determine ecological thre-shold were summarized, including locally weighted scatterplot smoothing, piecewise regression, Gaussian model, change-point analyzer, regime shift detection, threshold indicator taxa analysis and system dynamics simulation model. The advantages, disadvantages and applicability of those methods were also addressed. This study could provide references for quantitative detection of ecological threshold.

Preparation of mixed micelles carrying folates and stable radicals through PLA stereocomplexation for drug delivery.

Multifunctional mixed micelles possessing targeting folates on the periphery and stable radicals in the core were prepared from the mixture of folate-poly(ethylene glycol)-block-poly(d-lactide) (FA-PEG-b-PDLA) and poly(ethylene glycol) methyl ether-block-poly(l-lactide)- 2,2,6,6-tetramethylpiperidine-1-oxyl (mPEG-b-PLLA-TEMPO). FA-PEG-b-PDLA and mPEG-b-PLLA-TEMPO were prepared by combining ring-opening polymerization (ROP) of lactide with a series of conversion of the end functional groups. The synthesized block copolymers and their intermediates were well characterized by gel permeation chromatography (GPC) and 1H nuclear magnetic resonance (1H NMR) spectroscopy. The mixture of FA-PEG-b-PDLA and mPEG-b-PLLA-TEMPO self-assembled into spherical micelles with the average diameter about 200 nm through PLA stereocomplexation, which were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). The formed micelles were confirmed to emit electron paramagnetic resonance (EPR) signals by EPR spectroscopy. Additionally, the formed micelles exhibited high loading capacity of hydrophobic anticancer drug, controlled in vitro drug release, satisfied biocompatibility and a significantly higher cellular uptake, indicating promising applications in smart drug delivery.

Cyclodextrin based unimolecular micelles with targeting and biocleavable abilities as chemotherapeutic carrier to overcome drug resistance.

An amphiphilic star-shaped copolymer ß-CD-g-PCL-SS-PEG-FA, consisting of a ß-cyclodextrin (ß-CD) core as well as grafted with bioreducible disulfide linkage in PCL-SS-PEG multiarms and targeting folic acid (FA) as end moiety, is designed with unimolecular micelles formation ability for targeted transport of chemotherapeutics to drug resistant tumor cells. Firstly, ß-CD was utilized as core to growth PCL arms by ring-opening polymerization (ROP) of ε-CL, before disulfide terminal group transformation to render ß-CD-g-PCL-SS-COOH. Secondly, α-hydroxy-ω-amine protected PEG (HO-PEG-NHBoc) was connected to ß-CD-g-PCL-SS-COOH to obtain amphiphilic ß-CD-g-PCL-SS-PEG, where PCL and PEG were connected via bioreducible disulfide bond. After deprotection of -Boc group, FA was introduced onto the distal end of block arms to obtain the desired ß-CD-g-PCL-SS-PEG-FA copolymer. Because of highly branched core-shell amphiphilic structures, ß-CD-g-PCL-SS-PEG-FA could act as unimolecular micelles. Interestingly, this unimolecular micelle could release the encapsulated drug in a glutathione (GSH) dependent manner due to disulfide linkage. More importantly, this unimolecular micelle could load doxorubicin (DOX) to promote its cellular uptake in multidrug resistance (MDR) protein overexpression tumor cells, by taking the advantage of FA targeting group and intracellular high GSH level in cancer cells. Together with satisfactory biocompatibility, this novel star-like ß-CD-g-PCL-SS-PEG-FA unimolecular micelle could potentially be utilized as targeting nanocarriers in drug resistant cancer therapy.

ICAR ATRP Polymerization-Induced Self-Assembly Using a Mixture of Macroinitiator/Stabilizer with Different Molecular Weights.

The poly[oligo(ethylene oxide) methyl ether methacrylate]s, POEOMA24 and POEOMA78 with average degree of polymerization (DP) of 24 and 78, respectively, are separately achieved by initiators for continuous activator regeneration (ICAR) atom transfer radical polymerization (ATRP) of OEOMA300 monomer. The mixtures of [POEOMA24 ]0 /[POEOMA78 ]0 = 1/1, 2/1, or 4/1 are employed as macroinitiator/stabilizer to practice the ICAR ATRP polymerization-induced self-assembly (PISA) of benzyl methacrylate (BnMA) at 65 °C. When the obtained dispersions are sequentially cooled to room temperature, diluted into ethanol, and observed by transmission electron microscopy (TEM) measurement, the cases of [POEOMA24 ]0 /[POEOMA78 ]0 = 1/1 or 2/1 and target DPPB n MA = 100 or 200 lead to nanoparticles with irregular sizes, while the cases of [POEOMA24 ]0 /[POEOMA78 ]0 = 4/1 and target DPPB n MA = 300 give the regular ones. When the obtained dispersions at a high temperature (65 °C) are directly diluted into room temperature ethanol and observed by TEM, nanoparticles with light contrast but clear contour can be observed. The results show that the higher content of POEOMA78 tends to improve the solubility of diblock copolymer and thus leads to insufficient stabilization of the nanoparticles. The morphological difference from the room-temperature and 65 °C dispersions help elucidate the intrinsic character of the PISA system.

Reduction-responsive shell cross-linked micelles derived from amphiphilic triblock copolymer as anticancer drug delivery carrier.

Stimuli-responsive crosslinked micelles are attractive carriers for in vivo delivery of water-insoluble therapeutic drugs due to their excellent stability during the blood circulation and high therapeutic effect resulting from the intelligent break-up of the crosslinked structure triggered by intracellular conditions as well as the subsequent fast drug release. Herein, novel amphiphilic triblock copolymer poly(l-lactide)-b-poly(allyl glycidyl ether/propanedithiol)-b-poly(ethylene glycol) (PLLA-b-P(AGE-SH)-b-PEG) was designed and synthesized by combining two successive ring-opening polymerizations and subsequent "thio-ene" reaction. Due to their unique amphiphilic architecture, copolymer PLLA-b-P(AGE-SH)-b-PEG could self-assemble into core-shell micelles, and the stimuli-responsive crosslinked micelles (SCMs) were obtained by crosslinking the P(AGE-SH) segments in the micellar shell under redox condition. The SCMs exhibited good stability against extensive dilution and slow sustained drug release in a simulated normal physiologycal environment, but fast release in the presence of GSH. As revealed by the cytotoxicity assay, the micelles from the copolymer PLLA-b-P(AGE-SH)-b-PEG showed excellent biocompatibility against HEK293T cells. Due to these combined good properties, the stimuli-responsive crosslinked micelles from PLLA-b-P(AGE-SH)-b-PEG are proposed to be an ideal carrier for the in vivo delivery of water-insoluble therapeutics.

Polymeric Janus Nanoparticles: Recent Advances in Synthetic Strategies, Materials Properties, and Applications.

Polymeric Janus nanoparticles with two sides of incompatible chemistry have received increasing attention due to their tunable asymmetric structure and unique material characteristics. Recently, with the rapid progress in controlled polymerization combined with novel fabrication techniques, a large array of functional polymeric Janus particles are diversified with sophisticated architecture and applications. In this review, the most recently developed strategies for controlled synthesis of polymeric Janus nanoparticles with well-defined size and complex superstructures are summarized. In addition, the pros and cons of each approach in mediating the anisotropic shapes of polymeric Janus particles as well as their asymmetric spatial distribution of chemical compositions and functionalities are discussed and compared. Finally, these newly developed structural nanoparticles with specific shapes and surface functions orientated applications in different domains are also discussed, followed by the perspectives and challenges faced in the further advancement of polymeric Janus nanoparticles as high performance materials.

Cyclodextrin-Based Star-Like Amphiphilic Cationic Polymer as a Potential Pharmaceutical Carrier in Macrophages.

Effective delivery of therapeutic genes or small molecular drugs into macrophages is important for cell based immune therapy, but it remains a challenge due to the intracellular reactive oxygen species and endosomal degradation of therapeutics inside immune cells. In this report, the star-like amphiphilic biocompatible ß-cyclodextrin-graft-(poly(ε-caprolactone)-block-poly(2-(dimethylamino) ethyl methacrylate)x (ß-CD-g-(PCL-b-PDMAEMA)x ) copolymer, consisting of a biocompatible cyclodextrin core, hydrophobic poly(ε-caprolactone) PCL segments and hydrophilic PDMAEMA blocks with positive charge, is optimized to achieve high efficiency gene transfection with enhanced stability, due to the micelle formation by hydrophobic PCL segments. In comparison with lipofetamine, a currently popular nonviral gene carrier, ß-CD-g-(PCL-b-PDMAEMA)x copolymer, shows better transfection efficiency of plasmid desoxyribose nucleic acid in RAW264.7 macrophages. More interestingly, this delivery platform by ß-CD-g-(PCL-b-PDMAEMA)x not only shows low toxicity but also better dexamethasone delivery efficiency, which might indicate its great potential in immunotherapy.

Overcome the Conflict between Strength and Toughness in Poly(lactide) Nanocomposites through Tailoring Matrix-Filler Interface.

Strength and toughness are the two most important prerequisites for structural applications. Unfortunately, these two properties are often in conflict in materials. Here, an effective and yet practical strategy is proposed to simultaneously strengthen and toughen poly(l-lactide) (PLLA) using a simple rigid-rubber "reinforcing element." This element consists of a rigid graphene oxide (GO) sheet covalently coupled with poly(caprolactone-co-lactide) (PCLLA) rubbery layers, which can be easily synthesized and incorporated into PLLA matrix to develop composites with well-tailored GO/PLLA interfaces. It is demonstrated that by adding the "reinforcing element," i.e., GO-graft-rubber-graft-polyd-lactide), PLLA exhibits higher strength and higher toughness, which could be attributed to the synergy of rigid GO and rubbery PCLLA working in tandem during deformation. It is further demonstrated that this strategy can also be applied to other filler systems, such as clay and particulate polyhedral oligomeric silsesquioxane, and other polymer systems, such as poly(methyl methacrylate). The strategy could be considered as a general design principle for reinforcing materials where both strength and toughness are the key concerns.

Precise Synthesis of PS-PLA Janus Star-Like Copolymer.

In this work, an efficient strategy is designed for the precise synthesis of novel Janus star-like copolymer (polystyrene)8 -b-(poly(l-lactide))8 , (PLLA)8 -b-(PS)8 , consisting of two types of chemically distinct polymer arms, PS and PLLA, in an asymmetric structure. During the synthesis, PLLA hemisphere carrying protected hydroxyl groups at the focal point was first synthesized via a combined reactions of esterification, light-induced "Click" chemistry, and ring opening polymerization (ROP) using a specially designed dendron as initiator. After removing the protecting moiety, the terminal hydroxyl groups on the dendron segment is increased fourfold and further modified into bromopropionate-based macroinitiator through a two-step end group transformation reaction, followed by atom transfer radical polymerization (ATRP) of styrene to obtain the desired (PLLA)8 -b-(PS)8 Janus star-like copolymer. The versatility and efficiency of the designed synthetic strategy are demonstrated by the well-defined molecular characteristics and high yields of the targeted product. In addition to the controlled degradation behavior of the PLLA segments, the remaining bromide groups located at the distal end of PS arms could allow for further fabrication of diverse building blocks through consecutive ATRP of various monomers. This work signifies the first time for facile and precise synthesis of Janus star-like copolymer with unique biphasic structure and function control.

Stereocomplexed micelle formation through enantiomeric PLA-based Y-shaped copolymer for targeted drug delivery.

In this study, a novel stereocomplexed micelle system was prepared from the self-assembly of enantiomeric PLA-based Y-shaped copolymers, i.e. folic acid-adamantane/ß-cyclodextrin-b-[poly(D-lactide)]2 (FA-AD/CD-b-(PDLA)2) and poly(2-dimethylaminoethyl methacrylate)-b-[poly(L-lactide)]2 (PDMAEMA-b-(PLLA)2) in aqueous solution. The newly designed Y-shaped copolymer FA-AD/CD-b-(PDLA)2 was prepared by a combination of "click" reaction and host guest interaction between FA-AD and CD-b-(PDLA)2. In addition, enantiomeric Y-shaped PDMAEMA-b-(PLLA)2 copolymer was synthesized through ring-opening polymerization (ROP) of L-lactide using three-head initiator with bromo and -OH at distal ends, followed by atom transfer radical polymerization (ATRP) of DMAEMA to obtain the desired macromolecular architecture. The resultant copolymers and their intermediates were characterized by 1H nuclear magnetic resonance (1H NMR) and gel permeation chromatography (GPC) techniques. Due to the strong stereocomplexation interaction, FA-AD/CD-b-(PDLA)2 and PDMAEMA-b-(PLLA)2 mixture could self-assemble into stable mixed micelles in aqueous solution. Further, the stereocomplexed micelles exhibited excellent biocompatibility as revealed in the cytotoxicity assay. Together with the intrinsic biodegradability of PLA, it is envisioned that the stereocomplexed micelles developed in this study can be used as a promising nanocarrier for targeting drug delivery.

Hierarchically Self-Assembled Supramolecular Host-Guest Delivery System for Drug Resistant Cancer Therapy.

In this report, a new star-like copolymer ß-CD- g-(PNIPAAm- b-POEGA) x, consisting of a ß-CD core, grafted with temperature-responsive poly( N-isopropylacrylamide) (PNIPAAm) and biocompatible poly(oligo(ethylene glycol) acrylate) (POEGA) in a block copolymer of the arms, was used to deliver chemotherapeutics to drug resistant cancer cells and tumors. The first step of the self-assembly process involves the encapsulation of chemotherapeutics through host-guest inclusion complexation between the ß-cyclodextrin cavity and the anticancer drug. Next, the chain interaction of the PNIPAAm segment at elevated temperature drives the drug-loaded ß-CD- g-(PNIPAAm- b-POEGA) x/PTX inclusion complex to hierarchically self-assemble into nanosized supramolecular assemblies at 37 °C, whereas the presence of poly(ethylene glycol) (PEG) chains in the distal end of the star-like copolymer arms impart enhanced stability to the self-assembled structure. More interestingly, this supramolecular host-guest nanocomplex promoted the enhanced cellular uptake of chemotherapeutics in MDR-1 up-regulated drug resistant cancer cells and exhibited high therapeutic efficacy for suppressing drug resistant tumor growth in an in vivo mouse model, due to the increased stability, improvement in aqueous solubility, enhanced cellular uptake, and partial membrane pump impairment by taking the advantage of PEGylation and supramolecular complex between this star-like copolymer and chemotherapeutics. This work signifies that temperature-sensitive PEGylated supramolecular nanocarriers with good biocompatibility are effective in combating MDR-1 mediated drug resistance in both in vitro and in vivo models, which is of significant importance for the advanced drug delivery platform designed to combat drug resistant cancer.

Biodegradable polyester unimolecular systems as emerging materials for therapeutic applications.

Unimolecular micelles, as a class of single-molecular micelles, are structurally stable regardless of their concentrations or alterations of the outer environment such as pH, temperature, ion strength etc. in comparison with conventional polymeric micelles. Polyester unimolecular micelles are extensively applied in bio-medical fields because of their stability, biocompatibility, biodegradability, structural-controllabilty etc. In this review, the most recent developments in polyester unimolecular micelle designs in terms of Boltorn polymer H40 core, cyclodextrin, dendrimer or dendrimer-like polymer, or polyhedral oligomeric silsesquioxane (POSS) based polyester unimolecular micelles are presented. The significance and application in biomedical fields including drug delivery, bio-imaging and theranostics are also classified in this review. Finally, the remaining challenges and future perspectives for further development of unimolecular micelles as therapeutic materials are also discussed.