Overcoming Concealment Effects of Targeting Moieties in the PEG Corona: Controlled Permeable Polymersomes Decorated with Folate‐Antennae for Selective Targeting of Tumor Cells

In the context of diligent efforts to improve the tumor targeting efficiency of drug carriers, a shape‐persistent polymersome which possess a pH‐tunable membrane as well as folate targeting antennae is reported. The membrane of such polymersomes behaves as gate which undergoes “on” and “off” switches in response to pH stimuli. Thus, polymersomes can effectively prohibit the premature release of chemotherapeutic agents such as doxorubicin in physiological conditions, but promote drug release once they are triggered in the acidified endosomal compartment. Importantly, the folate moieties are installed on the surface of polymersomes as protruding antennae by doping the polymersomes with folate‐terminated block copolymers designed to have longer PEG segments. Thereby, the folate moieties are freed from concealment and steric effects exerted by the dense PEG corona. The cellular uptake of the FA‐antennae polymersomes by tumor cells is significantly enhanced facilitated by the freely accessible folate antennae; however, the normal cells record a low level of cellular uptake due to the stealth property of the PEG corona. Overall, the excellent biocompatibility, controlled permeability, targeted internalization, as well as selective cytotoxicity of such polymersomes set up the basis for properly smart carrier for targeted drug delivery.     

Light‐Driven Proton Transfer for Cyclic and Temporal Switching of Enzymatic Nanoreactors

Temporal activation of biological processes by visible light and subsequent return to an inactive state in the absence of light is an essential characteristic of photoreceptor cells. Inspired by these phenomena, light‐responsive materials are very attractive due to the high spatiotemporal control of light irradiation, with light being able to precisely orchestrate processes repeatedly over many cycles. Herein, it is reported that light‐driven proton transfer triggered by a merocyanine‐based photoacid can be used to modulate the permeability of pH‐responsive polymersomes through cyclic, temporally controlled protonation and deprotonation of the polymersome membrane. The membranes can undergo repeated light‐driven swelling–contraction cycles without losing functional effectiveness. When applied to enzyme loaded‐nanoreactors, this membrane responsiveness is used for the reversible control of enzymatic reactions. This combination of the merocyanine‐based photoacid and pH‐switchable nanoreactors results in rapidly responding and versatile supramolecular systems successfully used to switch enzymatic reactions ON and OFF on demand.     

Polymersome-loaded capsules for controlled release of DNA

The formation of a novel drug-delivery carrier for the controlled release of plasmid DNA that comprises layer-by-layer polymer capsules subcompartmentalized with pH-sensitive nanometer-sized polymersomes is reported. The amphiphilic diblock copolymer poly(oligoethylene glycol methacrylate)-block-poly(2-(diisopropylamino)ethyl methacrylate) forms polymersomes at physiological pH, but transitions to unimeric polymer chains upon acidification to cellular endocytic pH. These polymersomes can thus release an encapsulated payload in response to a change in pH from physiological to endocytic conditions. Multicomponent layer-by-layer capsules are formed by exploiting the ability of tannic acid to act as an efficient hydrogen-bond donor for both the polymersomes and poly(N-vinyl pyrrolidone) at physiological pH. These capsules show release of a plasmid DNA payload encapsulated within the polymersome subcompartments in response to changes in pH between physiological and endocytic conditions.     

Polymersomes Containing a Hydrogel Network for High Stability and Controlled Release

Capillary microfluidic devices are used to prepare monodisperse polymersomes consisting of a hydrogel core and a bilayer membrane of amphiphilic diblock‐copolymers. To make polymersomes, water‐in‐oil‐in‐water double‐emulsion drops are prepared as templates through single‐step emulsification in a capillary microfluidic device. The amphiphile‐laden middle oil phase of the double‐emulsion drop dewets from the surface of the innermost water drop, which contains hydrogel prepolymers; this dewetting leads to the formation of a bilayer membrane. Subsequently, the oil phase completely separates from the innermost water drop, leaving a polymersome. Upon UV illumination of the polymersome, the prepolymers encapsulated within the interior are crosslinked, forming a hydrogel core. The hydrogel network within the polymersomes facilitates sustained release of the encapsulated materials and increases the stability of the polymersomes through the formation of a scaffold to support the bilayer. In addition, this approach provides a facile method to make monodisperse hydrogel particles directly dispersed in water.     

Bioadhesive Polymersome for Localized and Sustained Drug Delivery at Pathological Sites with Harsh Enzymatic and Fluidic Environment via Supramolecular Host–Guest Complexation

Targeted and sustained delivery of drugs to diseased tissues/organs, where body fluid exchange and catabolic activity are substantial, is challenging due to the fast cleansing and degradation of the drugs by these harsh environmental factors. Herein, a multifunctional and bioadhesive polycaprolactone‐β‐cyclodextrin (PCL‐CD) polymersome is developed for localized and sustained co‐delivery of hydrophilic and hydrophobic drug molecules. This PCL‐CD polymersome affords multivalent crosslinking action via surface CD‐mediated host–guest interactions to generate a supramolecular hydrogel that exhibits evident shear thinning and efficient self‐healing behavior. The co‐delivery of small molecule and proteinaceous agents by the encapsulated PCL‐CD polymersomes enhances the differentiation of stem cells seeded in the hydrogel. Furthermore, the PCL‐CD polymersomes are capable of in situ grafting to biological tissues via host–guest complexation between surface CD and native guest groups in the tissue matrix both in vitro and in vivo, thereby effectively extending the retention of loaded cargo in the grafted tissue. It is further demonstrated that the co‐delivery of small molecule and proteinaceous drugs via PCL‐CD polymersomes averts cartilage degeneration in animal osteoarthritic (OA) knee joints, which are known for their biochemically harsh and fluidically dynamic environment.     

Effects of Water and Different Solutes on Carbon‐Nanotube Low‐Voltage Field‐Effect Transistors

Semiconducting single‐walled carbon nanotubes (swCNTs) are a promising class of materials for emerging applications. In particular, they are demonstrated to possess excellent biosensing capabilities, and are poised to address existing challenges in sensor reliability, sensitivity, and selectivity. This work focuses on swCNT field‐effect transistors (FETs) employing rubbery double‐layer capacitive dielectric poly(vinylidene fluoride‐co‐hexafluoropropylene). These devices exhibit small device‐to‐device variation as well as high current output at low voltages (<0.5 V), making them compatible with most physiological liquids. Using this platform, the swCNT devices are directly exposed to aqueous solutions containing different solutes to characterize their effects on FET current–voltage (FET I–V) characteristics. Clear deviation from ideal characteristics is observed when swCNTs are directly contacted by water. Such changes are attributed to strong interactions between water molecules and sp²‐hybridized carbon structures. Selective response to Hg²⁺ is discussed along with reversible pH effect using two distinct device geometries. Additionally, the influence of aqueous ammonium/ammonia in direct contact with the swCNTs is investigated. Understanding the FET I–V characteristics of low‐voltage swCNT FETs may provide insights for future development of stable, reliable, and selective biosensor systems.     

The Binary Effect on Methicillin‐Resistant Staphylococcus aureus of Polymeric Nanovesicles Appended by Proline‐Rich Amino Acid Sequences and Inorganic Nanoparticles

Prevalent research underscores efforts to engineer highly sophisticated nanovesicles that are functionalized to combat antibiotic‐resistant bacterial infections, especially those caused by methicillin‐resistant Staphylococcus aureus (MRSA), and that aid with wound healing or immunomodulation. This is especially relevant for patients who are susceptible to Staphylococcus aureus infections postoperatively. Here, antibacterial formulations are incorporated into polymeric, biocompatible vesicles called polymersomes (PsNPs) that self‐assemble via hydrophobic interactions of admixed aqueous and organic substances. Nano‐PsNPs are synthesized using a high molecular weight amphiphilic block copolymer, and are conjugated to include antimicrobial peptides (AMPs) along the peripheral hydrophilic region and silver nanoparticles (AgNPs) inside their hydrophobic corona. In vitro testing on bacterial and human cell lines indicates that finely tuned treatment concentrations of AMP and AgNPs in PsNPs synergistically inhibits the growth of MRSA without posing significant side effects, as compared with other potent treatment strategies. A ratio of silver‐to‐AMP of about 1:5.8 corresponding to ≈11.6 µg mL^?1 of silver nanoparticles and 14.3 × 10^?6 m of the peptide, yields complete MRSA inhibition over a 23 h time frame. This bacteriostatic activity, coupled with nominal cytotoxicity toward native human dermal fibroblast cells, extends the potential for AMP/AgNP polymersome therapies to replace antibiotics in the clinical setting.     

Poly(N‐phenylglycine)‐Based Nanoparticles as Highly Effective and Targeted Near‐Infrared Photothermal Therapy/Photodynamic Therapeutic Agents for Malignant Melanoma

Malignant melanoma is a highly aggressive tumor resistant to chemotherapy. Therefore, the development of new highly effective therapeutic agents for the treatment of malignant melanoma is highly desirable. In this study, a new class of polymeric photothermal agents based on poly(N‐phenylglycine) (PNPG) suitable for use in near‐infrared (NIR) phototherapy of malignant melanoma is designed and developed. PNPG is obtained via polymerization of N‐phenylglycine (NPG). Carboxylate functionality of NPG allows building multifunctional systems using covalent bonding. This approach avoids complicated issues typically associated with preparation of polymeric photothermal agents. Moreover, PNPG skeleton exhibits pH‐responsive NIR absorption and an ability to generate reactive oxygen species, which makes its derivatives attractive photothermal therapy (PTT)/photodynamic therapy (PDT) dual‐modal agents with pH‐responsive features. PNPG is modified using hyaluronic acid (HA) and polyethylene glycol diamine (PEG‐diamine) acting as the coupling agent. The resultant HA‐modified PNPG (PNPG‐PEG‐HA) shows negligible cytotoxicity and effectively targets CD44‐overexpressing cancer cells. Furthermore, the results of in vitro and in vivo experiments reveal that PNPG‐PEG‐HA selectively kills B16 cells and suppresses malignant melanoma tumor growth upon exposure to NIR light (808 nm), indicating that PNPG‐PEG‐HA can serve as a very promising nanoplatform for targeted dual‐modality PTT/PDT of melanoma.     

Controlling Cellular Uptake by Surface Chemistry,Size, and Surface Topology at the Nanoscale

Cell cytosol and the different subcellular organelles house the most important biochemical processes that control cell functions. Effective delivery of bioactive agents within cells is expected to have an enormous impact on both gene therapy and the future development of new therapeutic and/or diagnostic strategies based on single‐cell–bioactive‐agent interactions. Herein a biomimetic nanovector is reported that is able to enter cells, escape from the complex endocytic pathway, and efficiently deliver actives within clinically relevant cells without perturbing their metabolic activity. This nanovector is based on the pH‐controlled self‐assembly of amphiphilic copolymers into nanometer‐sized vesicles (or polymersomes). The cellular‐uptake kinetics can be regulated by controlling the surface chemistry, the polymersome size, and the polymersome surface topology. The latter is controlled by the extent of polymer–polymer phase separation within the external envelope of the polymersome.     

Stimuli‐Directed Colorimetric Interconversion of Helical Polymers Accompanied by a Tunable Self‐Assembly Process

Interconversion between extended and bent structures at the pendant groups of a chiral polyene framework [poly(phenylacetylene) with (R)‐(2‐methoxy‐2‐phenylacetyl)glycine residues linked to 4‐vinylanilines] allows the reversible colorimetric transformation from stretched to compressed helical cis‐transoid polyenic structures through manipulation of the flexible spacer. This transformation generates either organogels (stretched helical form) or nanoparticles (compressed helical form) under the control of polar/low polar stimuli respectively and opens the way to the development of new sensors and stimuli‐sensitive materials based on these concepts.     

Ultrahigh‐Conductivity Polymer Hydrogels with Arbitrary Structures

A poly(3,4‐ethylenedioxythiophene):poly(4‐styrenesulfonate) (PEDOT:PSS) hydrogel is prepared by thermal treatment of a commercial PEDOT:PSS (PH1000) suspension in 0.1 mol L^?1 sulfuric acid followed by partially removing its PSS component with concentrated sulfuric acid. This hydrogel has a low solid content of 4% (by weight) and an extremely high conductivity of 880 S m^?1. It can be fabricated into different shapes such as films, fibers, and columns with arbitrary sizes for practical applications. A highly conductive and mechanically strong porous fiber is prepared by drying PEDOT:PSS hydrogel fiber to fabricate a current‐collector‐free solid‐state flexible supercapacitor. This fiber supercapacitor delivers a volumetric capacitance as high as 202 F cm^?3 at 0.54 A cm^?3 with an extraordinary high‐rate performance. It also shows excellent electrochemical stability and high flexibility, promising for the application as wearable energy‐storage devices.     

Practical Approach in Developing Desirable Peel–Seal and Clear Lidding Films Based on Poly(Lactic Acid) and Poly(Butylene Adipate‐Co‐Terephthalate) Blends

In this research, poly(lactic acid) (PLA) blend with poly(butylene adipate‐co‐terephthalate) (PBAT) were selected to fabricate peelable lidding films. In general, blending PLA with PBAT results in hazy films; however, desirable low haze films (<10%) could be achieved in this study by designing proper blend composition and cast film process under optimum conditions. Based on various blends containing PBAT ranging from 15 to 30% by weight, it could be seen that a PBAT/PLA blend of 20/80 showed desired optical and peel–seal property, which had a haze of <10% and low peel strength in an easy‐peel characteristic. It was also observed that not only the blend composition but also the film thickness could influence both optical and peel–seal behaviours because the bulk morphology and surface irregularities of the films could vary by changing films' thicknesses. Thus, cast extruded pristine and PBAT/PLA (20/80) blend films of three different thicknesses (20, 35 and 50 μm) were studied. Peel–seal behaviour and optical properties of these films were examined. An I‐peel test (180°) of films sealed on PLA sheet (thickness of ~350 μm) with different interfacial sealing temperature illustrated failure mechanism of four types, i.e. tearing, partial tearing, cohesive and adhesive failure. Based on this study, the PBAT/PLA of 20/80 wt% films with thickness of 20 μm can be used as easy‐peel lidding film sealed with PLA container. Such PBAT/PLA blend films possess a low haze of ~4% and a low peel strength of 8–10 N/15 mm at a broad range of interfacial sealing temperature of 76–105°C. Copyright © 2017 John Wiley & Sons, Ltd.     

Goosebumps‐Inspired Microgel Patterns with Switchable Adhesion and Friction

A substrate mimicking the surface topography and temperature sensitivity of skin goosebumps is fabricated. Close‐packed arrays of thermoresponsive microgel particles undergo topographical changes in response to temperature changes between 25 and 37 °C, resembling the goosebump structure that human skin develops in response to temperature changes or other circumstances. Specifically, positively charged poly[2‐(methacryloyloxy)ethyltrimethylammonium chloride] (PMETAC) brushes serve as an anchoring substrate for negatively charged poly(NIPAm‐co‐AA) microgels. The packing density and particle morphology can be tuned by brush layer thickness and pH of the microgel suspension. For brush layer thickness below 50 nm, particle monolayers are observed, with slightly flattened particle morphology at pH 3 and highly collapsed particles at pH above 7. Polymer brush films with thickness above 50 nm lead to the formation of particle multilayers. The temperature responsiveness of the monolayer assemblies allows reversible changes in the film morphology, which in turn affects underwater adhesion and friction at 25 and 37 °C. These results are promising for the design of new functional materials and may also serve as a model for biological structures and processes.     

Erythrocyte‐Membrane‐Enveloped Perfluorocarbon as Nanoscale Artificial Red Blood Cells to Relieve Tumor Hypoxia and Enhance Cancer Radiotherapy

Hypoxia, a common feature within many types of solid tumors, is known to be closely associated with limited efficacy for cancer therapies, including radiotherapy (RT) in which oxygen is essential to promote radiation‐induced cell damage. Here, an artificial nanoscale red‐blood‐cell system is designed by encapsulating perfluorocarbon (PFC), a commonly used artificial blood substitute, within biocompatible poly(d ,l ‐lactide‐co‐glycolide) (PLGA), obtaining PFC@PLGA nanoparticles, which are further coated with a red‐blood‐cell membrane (RBCM). The developed PFC@PLGA‐RBCM nanoparticles with the PFC core show rather efficient loading of oxygen, as well as greatly prolonged blood circulation time owing to the coating of RBCM. With significantly improved extravascular diffusion within the tumor mass, owing to their much smaller nanoscale sizes compared to native RBCs with micrometer sizes, PFC@PLGA‐RBCM nanoparticles are able to effectively deliver oxygen into tumors after intravenous injection, leading to greatly relieved tumor hypoxia and thus remarkably enhanced treatment efficacy during RT. This work thus presents a unique type of nanoscale RBC mimic for efficient oxygen delivery into solid tumors, favorable for cancer treatment by RT, and potentially other types of therapy as well.     

Desktop‐Stereolithography 3D‐Printing of a Poly(dimethylsiloxane)‐Based Material with Sylgard‐184 Properties

The advantageous physiochemical properties of poly(dimethylsiloxane) (PDMS) have made it an extremely useful material for prototyping in various technological, scientific, and clinical areas. However, PDMS molding is a manual procedure and requires tedious assembly steps, especially for 3D designs, thereby limiting its access and usability. On the other hand, automated digital manufacturing processes such as stereolithography (SL) enable true 3D design and fabrication. Here the formulation, characterization, and SL application of a 3D‐printable PDMS resin (3DP‐PDMS) based on commercially available PDMS‐methacrylate macromers, a high‐efficiency photoinitiator and a high‐absorbance photosensitizer, is reported. Using a desktop SL‐printer, optically transparent submillimeter structures and microfluidic channels are demonstrated. An optimized blend of PDMS‐methacrylate macromers is also used to SL‐print structures with mechanical properties similar to conventional thermally cured PDMS (Sylgard‐184). Furthermore, it is shown that SL‐printed 3DP‐PDMS substrates can be rendered suitable for mammalian cell culture. The 3DP‐PDMS resin enables assembly‐free, automated, digital manufacturing of PDMS, which should facilitate the prototyping of devices for microfluidics, organ‐on‐chip platforms, soft robotics, flexible electronics, and sensors, among others.     

Stimuli‐Responsive,Shape‐Transforming Nanostructured Particles

Development of particles that change shape in response to external stimuli has been a long‐thought goal for producing bioinspired, smart materials. Herein, the temperature‐driven transformation of the shape and morphology of polymer particles composed of polystyrene‐b‐poly(4‐vinylpyridine) (PS‐b‐P4VP) block copolymers (BCPs) and temperature‐responsive poly(N‐isopropylacrylamide) (PNIPAM) surfactants is reported. PNIPAM acts as a temperature‐responsive surfactant with two important roles. First, PNIPAM stabilizes oil‐in‐water droplets as a P4VP‐selective surfactant, creating a nearly neutral interface between the PS and P4VP domains together with cetyltrimethylammonium bromide, a PS‐selective surfactant, to form anisotropic PS‐b‐P4VP particles (i.e., convex lenses and ellipsoids). More importantly, the temperature‐directed positioning of PNIPAM depending on its solubility determines the overall particle shape. Ellipsoidal particles are produced above the critical temperature, whereas convex lens‐shaped particles are obtained below the critical temperature. Interestingly, given that the temperature at which particle shape change occurs depends solely on the lower critical solution temperature (LCST) of the polymer surfactants, facile tuning of the transition temperature is realized by employing other PNIPAM derivatives with different LCSTs. Furthermore, reversible transformations between different shapes of PS‐b‐P4VP particles are successfully demonstrated using a solvent‐adsorption annealing with chloroform, suggesting great promise of these particles for sensing, smart coating, and drug delivery applications.     

Spray‐Dried Nanoparticle‐in‐Microparticle Delivery Systems (NiMDS) for Gene Delivery,Comprising Polyethylenimine (PEI)‐Based Nanoparticles in a Poly(Vinyl Alcohol) Matrix

Nucleic acid‐based therapies rely on efficient formulations for nucleic acid protection and delivery. As nonviral strategies, polymeric and lipid‐based nanoparticles have been introduced; however, biological efficacy and biocompatibility as well as poor storage properties due to colloidal instability and their unavailability as ready‐to‐use systems are still major issues. Polyethylenimine is the most widely explored and promising candidate for gene delivery. Polyethylenimine‐based polyplexes and their combination with liposomes, lipopolyplexes, are efficient for DNA or siRNA delivery in vitro and in vivo. In this study, a highly potent spray‐dried nanoparticle‐in‐microparticle delivery system is presented for the encapsulation of polyethylenimine‐based polyplexes and lipopolyplexes into poly(vinyl alcohol) microparticles, without requiring additional stabilizing agents. This easy‐to‐handle gene delivery device allows prolonged nanoparticle storage and protection at ambient temperature. Biological analyses reveal further advantages regarding profoundly reduced cytotoxicity and enhanced transfection efficacies of polyethylenimine‐based nanoparticles from the nanoparticle‐in‐microparticle delivery system over their freshly prepared counterparts, as determined in various cell lines. Importantly, this nanoparticle‐in‐microparticle delivery system is demonstrated as ready‐to‐use dry powder to be an efficient device for the inhalative delivery of polyethylenimine‐based lipopolyplexes in vivo, as shown by transgene expression in mice after only one administration.     

Smart Nanovehicles Based on pH‐Triggered Disassembly of Supramolecular Peptide‐Amphiphiles for Efficient Intracellular Drug Delivery

A novel type of nanovehicle (NV) based on stimuli‐responsive supramolecular peptide‐amphiphiles (SPAs, dendritic poly (L‐lysine) non‐covalently linked poly (L‐leucine)) is developed for intracellular drug delivery. To determine the pH‐dependent mechanism, the supramolecular peptide‐amphiphile system (SPAS) is investigated at different pH conditions using a variety of physical and chemical approaches. The pH‐triggered disassembly of SPAS can be attributed to the disappearance of non‐covalent interactions within SPAs around the isoelectric point of poly (L‐leucine). SPAS is found to encapsulate guest molecules at pH 7.4 but release them at pH 6.2. In this way, SPAS is able to act as a smart NV to deliver its target to tumor cells using intracellular pH as a trigger. The DOX‐loaded NVs are approximately 150 nm in size. In vitro release profiles and confocal laser scanning microscopy (CLSM) images of HepG2 cells confirm that lower pH conditions can trigger the disassembly of NVs and so achieve pH‐dependent intracellular DOX delivery. In vitro cytotoxicity of the DOX‐loaded NVs to HepG2 cells demonstrate that the smart NVs enhance the efficacy of hydrophobic DOX. Fluorescence‐activated cell sorting (FACS) and CLSM results show that the NVs can enhance the endocytosis of DOX into HepG2 cells considerably and deliver DOX to the nuclei.     

Self‐Suppression of Lithium Dendrite in All‐Solid‐State Lithium Metal Batteries with Poly(vinylidene difluoride)‐Based Solid Electrolytes

Polymer‐based electrolytes have attracted ever‐increasing attention for all‐solid‐state lithium (Li) metal batteries due to their ionic conductivity, flexibility, and easy assembling into batteries, and are expected to overcome safety issues by replacing flammable liquid electrolytes. However, it is still a critical challenge to effectively block Li dendrite growth and improve the long‐term cycling stability of all‐solid‐state batteries with polymer electrolytes. Here, the interface between novel poly(vinylidene difluoride) (PVDF)‐based solid electrolytes and the Li anode is explored via systematical experiments in combination with first‐principles calculations, and it is found that an in situ formed nanoscale interface layer with a stable and uniform mosaic structure can suppress Li dendrite growth. Unlike the typical short‐circuiting that often occurs in most studied poly(ethylene oxide) systems, this interface layer in the PVDF‐based system causes an open‐circuiting feature at high current density and thus avoids the risk of over‐current. The effective self‐suppression of the Li dendrite observed in the PVDF–LiN(SO₂F)₂ (LiFSI) system enables over 2000 h cycling of repeated Li plating–stripping at 0.1 mA cm^?2 and excellent cycling performance in an all‐solid‐state LiCoO₂||Li cell with almost no capacity fade after 200 cycles at 0.15 mA cm^?2 at 25 °C. These findings will promote the development of safe all‐solid‐state Li metal batteries.     

Solvent‐Induced Self‐Assembly Strategy to Synthesize Well‐Defined Hierarchically Porous Polymers

Porous polymers with well‐orchestrated nanomorphologies are useful in many fields, but high surface area, hierarchical structure, and ordered pores are difficult to be satisfied in one polymer simultaneously. Herein, a solvent‐induced self‐assembly strategy to synthesize hierarchical porous polymers with tunable morphology, mesoporous structure, and microporous pore wall is reported. The poly(ethylene oxide)‐b‐polystyrene (PEO‐b‐PS) diblock copolymer micelles are cross‐linked via Friedel–Crafts reaction, which is a new way to anchor micelles into porous polymers with well‐defined structure. Varying the polarity of the solvent has a dramatic effect upon the oleophobic/oleophylic interaction, and the self‐assembly structure of PEO‐b‐PS can be tailored from aggregated nanoparticles to hollow spheres even mesoporous bulk. A morphological phase diagram is accomplished to systematically evaluate the influence of the composition of PEO‐b‐PS and the mixed solvent component on the pore structure and morphology of products. The hypercrosslinked hollow polymer spheres provide a confined microenvironment for the in situ reduction of K₂PdCl₄ to ultrasmall Pd nanoparticles, which exhibit excellent catalytic performance in solvent‐free catalytic oxidation of hydrocarbons and alcohols.