Selenium in Photochemical Vapor Generation: Mechanism Study and Potential Nonchromatographic Speciation Analysis.

The mechanism of selenium in the UV photochemical vapor generation (PVG) process was investigated by the use of multiple analytical methods. It was found that the UV-induced photooxidation trapping of the generated volatile SeH2 should be responsible for the previous opinion of relative inertness of Se(VI) in PVG with formic acid. Furthermore, the formation of Se(IV) was found during the PVG process, and the comproportionation of Se(IV) with SeH2 and the photooxidation of Se(IV) into Se(VI) were investigated. Then, a preliminary model was proposed for the PVG process of Se(VI) and Se(IV) with low-molecular-weight organic acids. Then, a novel, simple, and green photocontrolled method without any photocatalyst was thus proposed for the nonchromatographic speciation analysis of Se(IV) and Se(VI), with a limit of detection of 0.2 and 5 ng/mL, respectively.

Prussian Blue-Assisted NIR Triggered In-Situ Polymerized Nanocomposite Hydrogel for Wound Repair.

Hydrogels are commonly used as wound dressings to help maintain a moist environment around the wound and isolate contaminants, thus promoting healing. For irregular wounds, the slow healing process and even infection may occur due to the inability of dressings to adhere well to the wound. Prussian blue (PB) is a metal-organic framework (MOF) material with excellent photothermal conversion and superior stability. In this paper, a kind of near-infrared (NIR) light triggered in-situ polymerized antimicrobial hydrogel was prepared. The free radical initiator was encapsulated in the hollow PB by a phase change material (PCM) to maintain stability. The raised temperature triggered by NIR induced the release and decomposition of the initiator. The matrix was formed by the cross-linking of double bonds on modified chitosan. The quaternary amine groups of modified chitosan and the photothermal properties of PB enhanced the antimicrobial properties of the hydrogel. High-quality wound healing was demonstrated in the whole skin defect model. This study provides a new reference for the preparation of in-situ polymerized hydrogel dressings for irregular wounds.

Improved Cell Adhesion on Self-Assembled Chiral Nematic Cellulose Nanocrystal Films.

Chirality is ubiquitous in nature, and closely related to biological phenomena. Nature-originated nanomaterials such as cellulose nanocrystals (CNCs) are able to self-assemble into hierarchical chiral nematic CNC films and impart handedness to nano and micro scale. However, the effects of the chiral nematic surfaces on cell adhesion are still unknown. Herein, this work presents evidence that the left-handed self-assembled chiral nematic CNC films (L-CNC) significantly improve the adhesion of L929 fibroblasts compared to randomly arranged isotropic CNC films (I-CNC). The fluidic force microscopy-based single-cell force spectroscopy is introduced to assess the cell adhesion forces on the substrates of L-CNC and I-CNC, respectively. With this method, a maximum adhesion force of 133.2 nN is quantified for mature L929 fibroblasts after culturing for 24 h on L-CNC, whereas the L929 fibroblasts exert a maximum adhesion force of 78.4 nN on I-CNC under the same condition. Moreover, the instant SCFS reveals that the integrin pathways are involved in sensing the chirality of substrate surfaces. Overall, this work offers a starting point for the regulation of cell adhesion via the self-assembled nano and micro architecture of chiral nematic CNC films, with potential practical applications in tissue engineering and regenerative medicine.

Targeting endothelial tight junctions to predict and protect thoracic aortic aneurysm and dissection.

AIMS: Whether changes in endothelial tight junctions (TJs) lead to the formation of thoracic aortic aneurysm and dissection (TAAD) and serve as an early indicator and therapeutic target remains elusive. METHODS AND RESULTS: Single-cell RNA sequencing analysis showed aberrant endothelial TJ expressions in the thoracic aortas of patients with TAAD. In a ß-aminopropionitrile (BAPN)-induced TAAD mouse model, endothelial TJ function was disrupted in the thoracic aortas at an early stage (5 and 10 days) as observed by a vascular permeability assay, while the intercellular distribution of crucial TJ components was significantly decreased by en face staining. For the non-invasive detection of endothelial TJ function, two dextrans of molecular weights 4 and 70 kDa were conjugated with the magnetic resonance imaging (MRI) contrast agent Gd-DOTA to synthesize FITC-dextran-DOTA-Gd and rhodamine B-dextran-DOTA-Gd. MRI images showed that both probes accumulated in the thoracic aortas of the BAPN-fed mice. Particularly, the mice with increased accumulated signals from 5 to 10 days developed TAAD at 14 days, whereas the mice with similar signals between the two time points did not. Furthermore, the protease-activated receptor 2 inhibitor AT-1001, which seals TJs, alleviated the BAPN-induced impairment of endothelial TJ function and expression and subsequently reduced TAAD incidence. Notably, endothelial-targeted ZO-1 conditional knockout increased TAAD incidence. Mechanistically, vascular inflammation and edema were observed in the thoracic aortas of the BAPN-fed mice, whereas these phenomena were attenuated by AT-1001. CONCLUSION: The disruption of endothelial TJ function is an early event prior to TAAD formation, herein serving as a potential indicator and a promising target for TAAD.

Rapid Regulation of Cardiomyocytes Adhesion on Substrates with Varied Modulus via Mechanical Cues.

In-depth understanding of the mechanisms underlying the adhesion of myocardial cells holds significant importance for the development of effective therapeutic biomaterials aimed at repairing damaged or pathological myocardial tissues. Herein, we present evidence that myocardial cells (H9C2) exhibit integrin-based mechanosensing during the initial stage of adhesion (within the first 2 h), enabling them to recognize and respond to variations in substrate stiffnesses. Moreover, the bioinformatics analysis of RNA transcriptome sequencing (RNA-seq) reveals that the gene expressions associated with initial stage focal adhesion (Ctgf, Cyr61, Amotl2, Prickle1, Serpine1, Akap12, Hbegf, and Nedd9) are up-regulated on substrates with elevated Young's modulus. The fluorescent immunostaining results also suggest that increased substrate stiffness enhances the expression of Y397-phosphorylated focal adhesion kinase (FAK Y397), talin, and vinculin and the assembly of F-actin in H9C2 cells, thereby facilitating the adhesion of myocardial cells on the substrate. Next, we utilize fluidic force microscopy (FluidFM)-based single-cell force spectroscopy (SCFS) to quantitatively evaluate the impact of substrate stiffness on the cell adhesion force and adhesion work, thus providing novel insights into the biomechanical regulation of initial cell adhesion. Our findings demonstrate that the maximum adhesion forces of myocardial cells exhibit a rise from 23.6 to 248.0 nN when exposed to substrates with different moduli. It is worth noting that once the αvß3 integrins are blocked, the disparities in the adhesion forces of myocardial cells on these substrates become negligible. These results exhibit remarkable sensitivity of myocardial cells to mechanical cues of the substrate, highlighting the role of αvß3 integrin as a biomechanical sensor for the regulation of cell adhesion. Overall, this work offers a prospective approach for the regulation of cell adhesion via integrin mechanosensing with potential practical applications in the areas of tissue engineering and regenerative medicine.

Recyclable fluorescence sensing based on copper clusters for simultaneous determination of copper ions and ammonia.

A one-step strategy for synthesizing fluorescent copper clusters stabilized by L-cysteine has been successfully established in aqueous solutions. The direct determination of copper ions was realized by the fluorescence enhancement phenomenon caused by the preparation and aggregation process. At the same time, ammonia treatment can lead to rapid fluorescence quenching, resulting from the influence on the aggregation behavior of Cu clusters, while the fluorescence can be recovered by the continuous addition of copper ions. Therefore, a recyclable fluorescence sensing system is constructed for the simultaneous determination of copper ions and ammonia. This method is simple, anti-interference and has been successfully applied to the determination of environmental samples.

A Targeting Singlet Oxygen Battery for Multidrug-Resistant Bacterial Deep-Tissue Infections.

Traditional photodynamic therapy (PDT) is dependent on externally applied light and oxygen, and the depth of penetration of these factors can be insufficient for the treatment of deep infections. The short half-life and short diffusion distance of reactive oxygen species (ROS) also limit the antibacterial efficiency of PDT. Herein, we designed a targeting singlet oxygen delivery system, CARG-Py, for irradiation-free and oxygen-free PDT. This system was converted to the "singlet oxygen battery" CARG-1 O2 and released singlet oxygen without external irradiation or oxygen. CARG-1 O2 is composed of pyridones coupled to a targeting peptide that improves the utilization of singlet oxygen in deep multidrug-resistant bacterial infections. CARG-1 O2 was shown to damage DNA, protein, and membranes by increasing the level of reactive oxygen inside bacteria; the attacking of multiple biomolecular sites caused the death of methicillin-resistant Staphylococcus aureus (MRSA). An in vivo study in a MRSA-infected mouse model of pneumonia demonstrated the potential of CARG-1 O2 for the efficient treatment of deep infections. This work provides a new strategy to improve traditional PDT for irradiation- and oxygen-free treatment of deep infections while improving convenience of PDT.

Nonylphenol regulates TL1A through the AhR/HDAC2/HNF4α pathway in endothelial cells to promote the angiogenesis of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most malignant cancers worldwide. Nonylphenol (NP) is an endocrine-disruptor chemical and plays an important role in the development of cancers. However, the effects of NP on CRC remain unclear. In this study, we aimed to investigate the potential mechanisms of NP in the pathogenesis of CRC. METHODS: The levels of AhR, TL1A and HDAC2 in CRC tissues and endothelial cells were assessed by RT-qPCR or western blot. CHIP and dual luciferase reporter assays were used to confirm the interaction between AhR and HDAC2, or HNF4α and TL1A. The CCK8, would healing and tube formation assays were conducted to evaluate the proliferation, migration and angiogenesis of HUVECs. Western blot determined HNF4α protein and HNF4α acetylation levels. The secreted TL1A protein was detected by ELISA. The angiogenesis-related factor CD31 was tested by IHC. RESULTS: The expression level of AhR was significantly up-regulated in CRC tissues and endothelial cells. Moreover, NP activated the AhR pathway mediated colorectal endothelial cell angiogenesis and proliferation, while TL1A overexpression resisted these effects caused by NP. Besides, NP was found to modulate HNF4α deacetylation through AhR/HDAC2 to inhibit TL1A. Furthermore, in vivo experiments proved that NP regulated CRC growth and angiogenesis via AhR/HDAC2/HNF4α/TL1A axis. CONCLUSION: This study revealed that NP promoted CRC growth and angiogenesis through AhR/HDAC2/HNF4α/TL1A pathway and could be a new therapeutic target for CRC treatment.

Controllable Disulfide Exchange Polymerization of Polyguanidine for Effective Biomedical Applications by Thiol-Mediated Uptake.

New preparation methods of vectors are the key to developing the next generation of biomacromolecule delivery systems. In this study, a controllable disulfide exchange polymerization was established to obtain low-toxicity and efficient bioreducible polyguanidines (mPEG225 -b-PSSn , n=13, 26, 39, 75, 105) by regulating the concentration of activated nucleophiles and reaction time under mild reaction conditions. The relationship between the degrees of polymerization and biocompatibility was studied to identify the optimal polyguanidine mPEG225 -b-PSS26 . Such polyguanidine exhibited good in vitro performance in delivering different functional nucleic acids. The impressive therapeutic effects of mPEG225 -b-PSS26 were further verified in the 4T1 tumor-bearing mice as well as the mice with full-thickness skin defects. Controllable disulfide exchange polymerization provides an attractive strategy for the construction of new biomacromolecule delivery systems.

Site-Specific Scissors Based on Myeloperoxidase for Phosphorothioate DNA.

The tool box of site-specific cleavage for nucleic acid has been an increasingly attractive subject. Especially, the recent emergence of the orthogonally activatable DNA device is closely related to the site-specific scission. However, most of these cleavage strategies are based on exogenous assistance, such as laser irradiation. Endogenous strategies are highly desirable for the orthogonally regulatable DNA machine to explore the crucial intracellular biological process and cell signal network. Here, we found that the accurate site-specific cleavage reaction of phosphorothioate (PT) modified DNA by using myeloperoxidase (MPO). A scissors-like mechanism by which MPO breaks PT modification through chloride oxidation has been revealed. Furthermore, we have successfully applied the scissors to activate PT-modified hairpin-DNA machines to produce horseradish peroxidase (HRP)-mimicking DNAzyme or initiate hybridization chain reaction (HCR) amplification. Since MPO plays an important role in the pathway related to oxidative stress in cells, through the HCR amplification activated by this tool box, the oxidative stress in living cells has been robustly imaged. This work proposes an accurate and endogenous site-specific cleavage tool for the research of biostimuli and the construction of DNA molecular devices.

Optical Imaging in the Second Near Infrared Window for Vascular Bioimaging.

Optical imaging in the second near infrared region (NIR-II, 1000-1700 nm) provides higher resolution and deeper penetration depth for accurate and real-time vascular anatomy, blood dynamics, and function information, effectively contributing to the early diagnosis and curative effect assessment of vascular anomalies. Currently, NIR-II optical imaging demonstrates encouraging results including long-term monitoring of vascular injury and regeneration, real-time feedback of blood perfusion, tracking of lymphatic metastases, and imaging-guided surgery. This review summarizes the latest progresses of NIR-II optical imaging for angiography including fluorescence imaging, photoacoustic (PA) imaging, and optical coherence tomography (OCT). The development of current NIR-II fluorescence, PA, and OCT probes (i.e., single-walled carbon nanotubes, quantum dots, rare earth doped nanoparticles, noble metal-based nanostructures, organic dye-based probes, and semiconductor polymer nanoparticles), highlighting probe optimization regarding high brightness, longwave emission, and biocompatibility through chemical modification or nanotechnology, is first introduced. The application of NIR-II probes in angiography based on the classification of peripheral vascular, cerebrovascular, tumor vessel, and cardiovascular, is then reviewed. Major challenges and opportunities in the NIR-II optical imaging for vascular imaging are finally discussed.

Controlled Synthesis and Surface Engineering of Janus Chitosan-Gold Nanoparticles for Photoacoustic Imaging-Guided Synergistic Gene/Photothermal Therapy.

The unsymmetrical morphology and unique properties of Janus nanoparticles (JNPs) provide superior performances for biomedical applications. In this work, a general and facile strategy is developed to construct a series of symmetrical and unsymmetrical chitosan/gold nanoparticles. Taking advantage of the active motion derived from Janus structure, selective surface functionalization of polysaccharide domain, and photothermal effect of gold nanorods, Janus chitosan/gold nanoparticles (J-Au-CS) are selected as a model system to construct Janus-structured chitosan/gold nanohybrids (J-ACP). Near-infrared (NIR)-responsive J-ACP composed of polycationic chitosan nanospheres and PEGylated gold nanorods hold great potential to realize photoacoustic (PA) imaging-guided complementary photothermal therapy (PTT)/gene therapy for breast cancer. The morphology effect of chitosan/gold nanostructures on enhanced PTT, cellular uptake, and gene transfection is investigated. The feasibility of PA imaging to track the accumulation of J-ACP and guide PTT is also explored. Notably, synergistic therapy is achieved based on PTT-enhanced gene therapy. In addition, the loading function of chitosan/gold nanoparticles for fluorescence imaging is demonstrated. The current work extends the application of JNPs for imaging-guided synergistic cancer therapy and provides flexible candidates with distinct structures for diverse biomedical applications.

Versatile Types of Organic/Inorganic Nanohybrids: From Strategic Design to Biomedical Applications.

Organic/inorganic nanohybrids have attracted widespread interests due to their favorable properties and promising applications in biomedical areas. Great efforts have been made to design and fabricate versatile nanohybrids. Among different organic components, diverse polymers offer unique avenues for multifunctional systems with collective properties. This review focuses on the design, properties, and biomedical applications of organic/inorganic nanohybrids fabricated from inorganic nanoparticles and polymers. We begin with a brief introduction to a variety of strategies for the fabrication of functional organic/inorganic nanohybrids. Then the properties and functions of nanohybrids are discussed, including properties from organic and inorganic parts, synergistic properties, morphology-dependent properties, and self-assembly of nanohybrids. After that, current situations of nanohybrids applied for imaging, therapy, and imaging-guided therapy are demonstrated. Finally, we discuss the prospect of organic/inorganic nanohybrids and highlight the challenges and opportunities for the future investigations.

In Situ Preparation of Mechanically Enhanced Hydrogel via Dispersion Polymerization in Aqueous Solution.

Hydrogels with improved mechanical properties can expand to a greater range of applications. The fabrication of conventional toughened hydrogels typically requires precise modifications, multiple components, and complex steps. Here, a straightforward "one-step" polymerization method for the in situ preparation of hydrogels in aqueous solutions, is reported. Inspired by polymerization-induced self-assembly (PISA), water-miscible monomers are copolymerized during the hydrogel fabrication; the growing blocks eventually form physical bridges thus providing a mechanism for effective energy dissipation. The rheological and mechanical properties are evaluated and the results reveal that this strategy can be an effective approach to design mechanically enhanced hydrogels for a wide range of applications.

Low Power, Low Temperature and Atmospheric Pressure Plasma-Induced Polymerization: Facile Synthesis and Crystal Regulation of Covalent Organic Frameworks.

Low temperature and atmospheric pressure plasma-induced polymerization was demonstrated as a fast and facile strategy for tailoring of packing phase of COF-1 as well as preparing diverse covalent organic frameworks (COFs) including both two-dimensional (2D) COFs and three-dimensional (3D) COFs. By regulating the solvents, the fast construction of well-ordered AB staggered COF-1 and AA eclipsed COF-1 was facilely realized in minutes. The plasma approach presented here led to the rapid preparation of eight classical 2D COFs, including boronate ester-linkage (COF-5, COF-8 and COF-10), azine-linkage (NUS-2), ß-ketoenamine-linkage (TpPa, TPBD), imine-linkage (ILCOF-1, Py-COF), and 3D-COF-102 (boroxine linkage) in less than 1 hour. Different from conventional methods, the proposed methodology required much less time, lower power, no extra heating, inert-gas protection and pressure. The fast nucleation and growth of COFs with good crystallinity, morphology and thermal stability can be achieved under mild conditions.

Molecular Sizes and Antibacterial Performance Relationships of Flexible Ionic Liquid Derivatives.

Cationic agents, such as ionic liquids (ILs)-based species, have broad-spectrum antibacterial activities. However, the antibacterial mechanisms lack systematic and molecular-level research, especially for Gram-negative bacteria, which have highly organized membrane structures. Here, we designed a series of flexible fluorescent diketopyrrolopyrrole-based ionic liquid derivatives (ILDs) with various molecular sizes (1.95-4.2 nm). The structure-antibacterial activity relationships of the ILDs against Escherichia coli (E. coli) were systematically studied thorough antibacterial tests, fluorescent tracing, morphology analysis, molecular biology, and molecular dynamics (MD) simulations. ILD-6, with a relatively small molecular size, could penetrate through the bacterial membrane, leading to membrane thinning and intracellular activities. ILD-6 showed fast and efficient antimicrobial activity. With the increase of molecular sizes, the corresponding ILDs were proven to intercalate into the bacterial membrane, leading to the destabilization of the lipid bilayer and further contributing to the antimicrobial activities. Moreover, the antibacterial activity of ILD-8 was limited, where the size was not large enough to introduce significant membrane disorder. Relative antibacterial experiments using another common Gram-negative bacteria, Pseudomonas aeruginosa (PAO1), further confirmed the proposed structure-antibacterial activity relationships of ILDs. More impressively, both ILD-6 and ILD-12 displayed significant in vivo therapeutic effects on the PAO1-infected rat model, while ILD-8 performed poorly, which confirmed the antibacterial mechanism of ILDs and proved their potentials for future application. This work clarifies the interactions between molecular sizes of ionic liquid-based species and Gram-negative bacteria and will provide useful guidance for the rational design of high-performance antibacterial agents.

Flexible Photothermal Assemblies with Tunable Gold Patterns for Improved Imaging-Guided Synergistic Therapy.

Self-assembly of gold nanoparticles demonstrates a promising approach to realize enhanced photoacoustic imaging (PAI) and photothermal therapy (PTT) for accurate diagnosis and efficient cancer therapy. Herein, unique photothermal assemblies with tunable patterns of gold nanoparticles (including arcs, rings, ribbons, and vesicles) on poly(lactic-co-glycolic acid) (PLGA) spheres are constructed taking advantage of emulsion-confined and polymer-directed self-assembly strategies. The influencing factors and formation mechanism to produce the assemblies are investigated in details. Both the emulsion structure and migration behaviors of amphiphilic block copolymer tethered gold nanoparticles are found to contribute to the formation of versatile photothermal assemblies. Hyaluronic acid-modified R-PLGA-Au (RPA) exhibits outstanding photothermal performances under NIR laser irradiation, which is induced by strong plasmonic coupling between adjacent gold nanoparticles. It is interesting that secondary assembly of RPA can be triggered by NIR laser irradiation. Prolonged residence time in tumors is achieved after RPA assemblies are fused into superstructures with larger sizes, realizing real-time monitoring of the therapeutic processes via PAI with enhanced photoacoustic signals. Notably, synergistic effect resulting from PTT-enhanced chemotherapy is realized to demonstrate high antitumor performance. This work provides a facile strategy to construct flexible photothermal assemblies with favorable properties for imaging-guided synergistic therapy.

Functional Nanocomplexes with Vascular Endothelial Growth Factor A/C Isoforms Improve Collateral Circulation and Cardiac Function.

Protein-based therapies are potential treatments for cancer, immunological, and cardiovascular diseases. However, effective delivery systems are needed because of their instability, immunogenicity, and so on. Crosslinked negatively charged heparin polysaccharide nanoparticle (HepNP) is proposed for protein delivery. HepNP can efficiently condense vascular endothelial growth factor (VEGF) because of the unique electronegative sulfonic acid and carboxyl domain of heparin. HepNP is then assembled with VEGF-C (Hep@VEGF-C) or VEGF-A (Hep@VEGF-A) protein for the therapy of myocardial infarction (MI) via intravenous (iv) injection. Hep@VEGF-A-mediated improvement of cardiac function by promoting angiogenesis is limited because of elevated vascular permeability, while Hep@VEGF-C effectively promotes lymphangiogenesis and reduces edema. On this basis, a graded delivery of VEGF-C (0.5-1 h post-MI) and VEGF-A (5 d post-MI) using HepNP is developed. At the dose ratio of 3:1 (Hep@VEGF-C vs Hep@VEGF-A), Hep@VEGF functional complexes substantially reduce the scar formation (≈-39%; p < 0.05) and improve cardiac function (≈+74%; p < 0.05). Such a HepNP delivery system provides a simple and effective therapeutic strategy for cardiovascular diseases by delivering functional proteins. Because of the unique binding ability of heparin with cytokines and growth factors, HepNP also has considerable application prospects in protein therapy for other serious diseases.

Gradient Functionalization of Various Quaternized Polyethylenimines on Microfluidic Chips for the Rapid Appraisal of Antibacterial Potencies.

The ability to appraise antibacterial potencies of surface-immobilized bactericidal polymers is still a major challenge in the engineering of antibacterial surfaces to combat hospital-acquired (nosocomial) infections. In this work, we fabricated a microfluidic platform with gradiently immobilized bactericidal polymers to enable the rapid appraisal of antibacterial potencies by in situ live/dead staining of bacteria. To this end, a variety of synthetic quaternary polymers, named QPEI-C1, QPEI-C6, QPEI-C8, and QPEI-C10, were gradiently immobilized in microfluidic channels, and their surface densities at different distances along the channels were quantified by using fluorescein-labeled polymers. We found that the surface densities of quaternary polymers could be well-tuned, and the length of the channel, resulting in a 50% reduction of live bacteria (L50), can be used to appraise the antibacterial potency of each bactericidal polymer. For instance, the L50 values of QPEI-C6-, QPEI-C8-, and QPEI-C10-modified channels against Escherichia coli were 35.5, 44.7, and 49.2 mm, respectively, indicating that QPEI-C10 exerted the most potent antibacterial efficacy. More importantly, this microfluidic platform enabled the rapid discrimination of antibacterial potencies of polymers (e.g., QPEI-C8, and QPEI-C10) while the conventional live/dead staining method found no significant difference. This work provides a powerful toolkit by combining advances of microfluidic systems and polymer science for the rapid screening of antibacterial coatings, which would find applications in surface modification of medical devices to combat bacterial infections.

Tunable Adhesion of Different Cell Types Modulated by Thermoresponsive Polymer Brush Thickness.

Tunable adhesion of different cell types on well-defined surfaces has attracted common interests in the field of biomaterial science and surface engineering. Herein, we demonstrate a new strategy for the regulation of cell adhesion by simply controlling the thickness of thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes via surface-initiated atom transfer radical polymerization (ATRP). The adhesion of different cell types (4T1, HEK293, H9C2, HUVEC, and L929) can be easily modulated by varying the thickness of PNIPAAm brushes from 5.9 ± 1.0 nm (PN1) to 69.0 ± 5.0 nm (PN6). The fluorescent staining of different cell types on a variety of surfaces reveals that the thickness of PNIPAAm brushes would regulate the assembly of F-actin and the expression of vinculin and fibronectin, which are essential in regulating the adherent status of cells. Moreover, the cellular morphologies revealed that the adherent cells are well-spread, and multiple pseudopod extensions and protrusions can be observed at the margin of cells. This work provides a facile strategy for regulating tunable adhesion of different cell types, which may find applications in tissue engineering and regenerative medicine.