Adhesion Proteins Research Articles

Molecular control of PDPNhi macrophage subset induction by ADAP as a host defense in sepsis.

Induction of podoplanin (PDPN) expression is a critical response of macrophages to LPS stimulation or bacterial infection in sepsis, but how this key process of TLR4-stimulated PDPN upregulation is regulated and the impact of PDPN expression on macrophage function remain elusive. Here, we determined how this process is regulated in vitro and in vivo. PDPN failed to be upregulated in TLR4 stimulated macrophages deficient in adhesion and degranulation-promoting adapter protein (ADAP), which could be rescued by the reconstitution of ADAP. A distinct PDPNhi peritoneal macrophage (PM) subset, which exhibited an M2-like phenotype and enhanced phagocytic activity, was generated in WT but not in ADAP-deficient septic mice. The blockade of PDPNhi PMs mimicked the effect of ADAP deficiency, which exacerbated sepsis. Mechanistically, BTK-mediated ADAP Y571 phosphorylation worked together with mTOR to converge on STAT3 activation for the transactivation of the PDPN promoter. Moreover, agonist activation of STAT3 profoundly potentiated the PDPNhi PM subset generation and alleviated sepsis severity in mice. Together, our findings reveal a mechanism whereby ADAP resets macrophage function by controlling the TLR4-induced upregulation of PDPN as a host innate immune defense during sepsis.

Efficacy and Cellular Mechanism of Biomimetic Marine Adhesive Protein-Based Coating Against Skin Photoaging.

Skin photoaging is a problem worldwide, clinically often accompanied by collagen decline, increased wrinkles, loss of skin elasticity, structurally weakened skin, and other complications,which urgently demand effective treatment strategies. The biosafety and efficacy of single-function therapies for repairing skin photoaging are still challenging for clinical medicine today. At present, numerous studies report that the wet adhesive proteins driven from marine organisms play a critical role in the biomedical material field, particularly in aquatic environments. In this study, a natural recombinant protein-based coating from scallop byssal protein is prepared to investigate the efficacy and cellular mechanism in accelerating the repair of UVB-induced photoaging in a mouse model. In vitro experiments demonstrate the safety of the coating and its efficacy in enhancing cell adhesion, spreading, proliferation, and migration. Additionally, the coating effectively scavenges reactive oxygen species, promotes the expression of cell adhesion molecules and anti-apoptotic proteins, and inhibits inflammatory responses. In animal tests, the coating exhibited remarkable adsorption properties, showing significant potential for in situ regenerative therapy, as evidenced by its ability to protect against UVB-induced skin photoaging and oxidative stress. These findings suggest that Sbp9Δ coating provides a simple, safe, and innovative strategy for treating skin photoaging.

GW4064 inhibits migration and invasion in human glioblastoma multiforme through the downregulation of PKCα.

Glioblastoma multiforme (GBM) is a deadly type of brain tumor with low patient survival rates. Previous studies have shown that inhibiting the intracellular bile acid transport protein can suppress brain tumor growth, migration, and angiogenesis. This study aims to investigate the effects of the bile acid nuclear receptor (farnesoid X receptor, FXR) agonist GW4064 on the migration, and invasion in GBM cells. GW4064 treatment inhibited the migration and invasion of GBM cells. The protein expression of phosphorylated focal adhesion kinase and protein kinase C alpha (PKCα) and activity of matrix metalloproteinase-2 (MMP2) were decreased by GW4064. The PKC activator phorbol 12-myristate 13-acetate (PMA) reversed the GW4064-reduced invasion ability in LN229 cells. Moreover, GW4064 combined with temozolomide (TMZ) treatment inhibited tumor progression in null mice. According to the hematoxylin and eosin stain (HE) and immunostaining, the tumor area and p-PKCα were reduced in the GW4064 combined with TMZ group. These results suggested that GW4064 declined the progression of GBM cells, with the inhibition of invasion mediated through PKC signaling. Targeting FXR may contribute to future therapeutic strategies for GBM.

The accessory secretion system in Streptococcus agalactiae regulates protein secretion, stress resistance, adhesion, immune evasion, and virulence.

Streptococcus agalactiae is a significant co-pathogenic bacterium in humans and animals, including fish. Bacteria secrete a variety of proteins through an accessory secretion system to modulate their interactions with the host. To investigate the role of the accessory secretion system in S. agalactiae, a deletion mutant strain (ΔaccSec) was constructed via homologous recombination. The accessory secretion system was found to be essential for the viability of S. agalactiae, and its absence led to increased cell death and lysis. In the extracellular fraction of the ΔaccSec mutant, a reduction in the secretion of 33 proteins was observed. Analyses of biological properties indicated that ΔaccSec exhibited significantly reduced stress tolerance and envelope stability. Pathogenicity experiments demonstrated that the ΔaccSec mutant had significantly lower adhesion to cells and fish tissues, as well as decreased resistance to whole blood killing and phagocytosis by macrophages. The cumulative mortality of ΔaccSec in tilapia after intraperitoneal injection was reduced by 55.3-74.2%. The ΔaccSec mutant exhibited a markedly diminished capacity for colonization in tilapia. Furthermore, we found that ΔaccSec mutant induced higher macrophage reactive oxygen species (ROS) levels and significantly upregulated MHC-II, TLR-2 transcript levels in tilapia spleens compared to the wild-type. Overall, these findings underscore the importance of the accessory secretion system in S. agalactiae pathogenicity, particularly in stabilizing the bacterial envelope, facilitating adhesion, and evading host immunity. The results of this study provide new insights into the mechanisms of virulence regulation in S. agalactiae and lay a foundation for developing live attenuated vaccines.

Exploring Nectin-4 expression in hepatocellular carcinoma.

632 Background: Nectin cell adhesion protein 4 (Nectin-4) is overexpressed in various malignancies, contributing to cancer progression and poor prognosis. We aimed to assess Nectin-4 expression in hepatocellular carcinoma (HCC). Methods: Patients who underwent primary liver tumor resection for HCC upon initial diagnosis at National Taiwan University Hospital in 2019 were included. Exclusion criteria consisted of prior systemic or loco-regional therapy, or death within three months post-surgery. Immunohistochemical (IHC) staining for Nectin-4 (EPR15613-68, Abcam) was conducted and independently reviewed by two pathologists. Nectin-4 expression patterns (membranous, cytoplasmic, and nuclear) and intensity were scored on a 0–3 scale, with normal eccrine glands (2+) serving as a positive control. Nectin-4 expression was further assessed in primary and paired progressive or metastatic tissue samples from patients with available paired samples. Results: Of the 193 patients, 175 had specimens available for IHC analysis. Nectin-4 expression was detected in 22.9% of these patients, with intensity scores of 0 in 77.1%, 1 in 22.3%, and 2 in 0.6%. The majority of staining pattern was cytoplasmic (94.3%), with membranous staining observed in 5.1% of cases. Nectin-4 expression was significantly associated with higher pathological grades ( p = 0.005) but showed no correlation with recurrence-free survival ( p = 0.771) or overall survival ( p = 0.396) after surgery. Importantly, Nectin-4 expression intensity significantly increased in paired progressive or metastatic samples compared to initial HCC specimens ( p = 0.046; n = 27). Conclusions: Nectin-4 expression is associated with higher pathological grades but not related to clinical outcomes in HCC. Increased Nectin-4 expression in progressive or metastatic disease highlights its potential as a therapeutic target.

From Vision Correction to Drug Delivery: Unraveling the Potential of Therapeutic Contact Lens.

Contact lenses (CLs) have become an essential tool in ocular drug delivery, providing effective treatment options for specific eye conditions. In recent advancements, Therapeutic CLs (TCLs) have emerged as a promising approach for maintaining therapeutic drug concentrations on the eye surface. TCLs offer unique attributes, including prolonged wear and a remarkable ability to enhance the bioavailability of loaded medications by more than 50%, thus gaining widespread usage. They have proven beneficial in pain management, medication administration, corneal healing, and protection. To achieve sustained drug delivery from TCLs, researchers are exploring diverse systems, such as polymeric nanoparticulate systems, lipidic systems, and the incorporation of agents like vitamin E or rate-limiting polymers. However, despite breakthrough successes, certain challenges persist, including ensuring drug stability during processing and manufacturing, controlling release kinetics, and biomaterial interaction, reducing protein adhesion, and addressing drug release during packaging and storage etc. While TCLs have shown overall success in treating corneal and ocular surface disorders, careful consideration of potential issues and contraindications is vital. This review offers an insightful perspective on the critical aspects that need to be addressed regarding TCLs, with a specific emphasis on their advantages and limitations.

Outside-in engineering of cadherin endocytosis using a conformation strengthening antibody

P-cadherin, a crucial cell-cell adhesion protein which is overexpressed in numerous malignant cancers, is a popular target for drug delivery antibodies. However, molecular guidelines for engineering antibodies that can be internalized upon binding to P-cadherin are unknown. Here, we use a combination of biophysical, biochemical, and cell biological methods to demonstrate that trapping the P-cadherin extracellular region in an X-dimer adhesive conformation triggers cadherin endocytosis via an outside-in signaling mechanism. We show that the anti-cancer drug delivery monoclonal antibody CQY684, traps P-cadherin in an X-dimer conformation and strengthens this adhesive structure. Formation of stable X-dimers results in the phosphorylation of p120-catenin, a suppressor of cadherin endocytosis. This triggers the dissociation of p120-catenin from the X-dimer cytoplasmic region, which increases P-cadherin turnover and targets the cadherin-antibody complex to the lysosome. Our results establish an outside-in signaling mechanism that provides fundamental insights into how cells regulate adhesion and that can be exploited by anti-cadherin antibodies for intracellular drug delivery.

G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration.

The subcellular localization of mRNAs plays a pivotal role in biological processes, including cell migration. For instance, β-actin mRNA and its associated RNA-binding protein (RBP), ZBP1/IGF2BP1, are recruited to focal adhesions (FAs) to support localized β-actin synthesis, crucial for cell migration. However,whether other mRNAs and RBPs also localize at FAs remains unclear. Here, we identify hundreds of mRNAs that are enriched at FAs (FA-mRNAs). FA-mRNAs share characteristics with stress granule (SG) mRNAs and are found in ribonucleoprotein (RNP) complexes with the SG RBP. Mechanistically, G3BP1 binds to FA proteins in an RNA-dependent manner, and its RNA-binding and dimerization domains, essential for G3BP1 to form RNPs in SG, are required for FA localization and cell migration. We find that G3BP1 RNPs promote cell speed by enhancing FA protein mobility and FA size. These findings suggest a previously unappreciated role for G3BP1 RNPs in regulating FA function under non-stress conditions.

Enhancing Bioactivity of Titanium-Based Materials Through Chitosan Based Coating and Calcitriol Functionalization.

Titanium (Ti)-based materials are favored for hard tissue applications, yet their bioinertness limits their success. This study hypothesizes that functionalizing Ti materials with chitosan nano/microspheres and calcitriol (VD) will enhance their bioactivity by improving cellular activities and mineralization. To test this, chitosan particles were applied uniformly onto Ti surfaces using electrophoretic deposition (EPD) at 20V for 3 minutes. VD was then loaded onto the coated surfaces, and the release profile of VD was monitored. Human fetal osteoblastic cells (hFOB) were cultured on the VD-loaded Ti surfaces. Cellular activities such as proliferation, Alkaline phosphatase (ALP) activity, osteogenic gene expression (runt-related transcription factor 2 (Runx2), collagen type 1 (Col I), osteocalcin ( OCn), osteopontin (OP)), and mineralization were assessed. Von Kossa staining was performed to analyze mineralization, and the expression of cell adhesion proteins (N-cadherin (NC), integrin alpha V (IaV), integrin beta 3, (Ib3)) was measured. The results showed that approximately 50% of the VD released over 50 hours. The chitosan coating increased surface roughness three-fold, and this, combined with VD release, resulted in reduced cell proliferation but increased ALP activity, suggesting enhanced differentiation. VD-functionalized Ti surfaces showed statistically significant differences in osteogenic gene expressions, particularly on rougher surfaces. Additionally, the expression of cell adhesion proteins (NC, IaV, Ib3) was upregulated on VD-containing coated surfaces. Von Kossa analysis revealed that surface roughness significantly enhanced mineralization, particularly on VD-free surfaces by day 7, while mineralization on VD-containing bare surfaces started on day 14. These findings demonstrate that VD-loaded chitosan coatings significantly enhance the biocompatibility and bioactivity of Ti-based materials, highlighting their potential for applications in bone regeneration.

An Anticoagulant Coating Based on a Block Phosphocholine Copolymer for Potential Applications in Blood Contact Devices

AbstractAs the core component of ventricular assist devices, blood pumps have been widely used in clinical treatment. However, the thrombus caused by the contact of the inner surface of the blood pumps with blood still remain a serious risk. The zwitterionic coating has the ability to form a hydration layer to inhibit the protein and blood cell adhesion, which makes it a potential strategy to solve the coagulation on the device. Herein, a phosphocholine zwitterionic coating is presented and formed by a block copolymer poly(2‐methylacryloxyethyl phosphatecholine‐b‐glycidyl methacrylate (PMPC‐b‐GMA). Poly(MPC) and poly(GMA) are intended to provide, respectively, resistance to thrombus formation and adhesion to the material surface. The copolymers are synthesized through reversible addition‐fragmentation chain transfer polymerization to achieve an accurate molecular design. After dip‐coated on the materials, the phosphocholine coating exhibits protein and platelet resistance ability, anticoagulant ability, and in vitro biocompatibility. Furthermore, the in vivo biocompatibility is confirmed through the implantation of the coated polycarbonate substrate in rats. This study provides a promising pathway for regulating the interaction between biomaterials and proteins, platelets, and bioactive molecules, and is expected to guide the further development of anticoagulant coatings to ensure the safety of blood contact devices in clinical treatment.

Codon usage analysis in selected virulence genes of Staphylococcal species.

The Staphylococcus genus, composed of Gram-positive bacteria, includes several pathogenic species such as Staphylococcus aureus, S. epidermidis, S. haemolyticus, and S. saprophyticus, each implicated in a range of infections. This study investigates the codon usage patterns in key virulence genes, including Autolysin (alt), Elastin Binding protein (EbpS), Lipase, Thermonuclease, Intercellular Adhesion Protein (IcaR), and V8 Protease, across four Staphylococcus species. Using metrics such as the Effective Number of Codons (ENc), Relative Synonymous Codon Usage (RSCU), Codon Adaptation Index (CAI), alongside neutrality and parity plots, we explored the codon preferences and nucleotide composition biases. Our findings revealed a pronounced AT-rich codon preference, with AT-rich genomes likely aiding in energy-efficient translation and bacterial survival in host environments. These insights provide a deeper understanding of the evolutionary adaptations and translational efficiency mechanisms that contribute to the pathogenicity of Staphylococcus species. This knowledge could pave the way for novel therapeutic interventions targeting codon usage to disrupt virulence gene expression.

Microenvironment actuated CAR T cells improve solid tumor efficacy without toxicity.

A major limiting factor in the success of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors is targeting tumor antigens also found on normal tissues. CAR T cells against GD2 induced rapid, fatal neurotoxicity because of CAR recognition of GD2+ normal mouse brain tissue. To improve the selectivity of the CAR T cell, we engineered a synthetic Notch receptor that selectively expresses the CAR upon binding to P-selectin, a cell adhesion protein overexpressed in tumor neovasculature. These tumor microenvironment actuated T (MEAT) cells ameliorated T cell infiltration in the brain, preventing fatal neurotoxicity while maintaining antitumor efficacy. We found that conditional CAR expression improved the persistence of tumor-infiltrating lymphocytes because of enhanced metabolic fitness of MEAT cells and the infusion of a less differentiated product. This approach increases the repertoire of targetable solid tumor antigens by restricting CAR expression and subsequent killing to cancer cells only and provides a proof-of-concept model for other targets.

Implant-Derived S. aureus Isolates Drive Strain-Specific Invasion Dynamics and Bioenergetic Alterations in Osteoblasts

Background: Implants are integral to modern orthopedic surgery. The outcomes are good, but infections remain a serious issue. Staphylococcus aureus (S. aureus), along with Staphylococcus epidermidis, are predominant pathogens responsible for implant-associated infections, as conventional antibiotic treatments often fail due to biofilm formation or the pathogens’ ability to invade cells and to persist intracellularly. Objectives: This study therefore focused on interactions of S. aureus isolates from infected implants with MG63 and SaOS2 osteoblasts by investigating the adhesion, invasion, and the impact on the bioenergetics of osteoblasts. Methods and Results: We found that the ability of S. aureus to adhere to osteoblasts depends on the isolate and was not associated with a single gene or expression pattern of characteristic adhesion proteins, and further, was not correlated with invasion. However, analysis of invasion capabilities identified better invasion conditions for S. aureus isolates with the SaOS2 osteoblastic cells. Interestingly, metabolic activity of osteoblasts remained unaffected by S. aureus infection, indicating cell survival. In contrast, respiration assays revealed an altered mitochondrial bioenergetic turnover in infected cells. While basal as well as maximal respiration in MG63 osteoblasts were not influenced statistically by S. aureus infections, we found increased non-mitochondrial respiration and enhanced glycolytic activity in the osteoblasts, which was again, more pronounced in the SaOS2 osteoblastic cells. Conclusions: Our findings highlight the complexity of S. aureus-host interactions, where both the pathogen and the host cell contribute to intracellular persistence and survival, representing a major factor for therapeutic failures.

Prognostic Implications of Decorin, E-Cadherin and EGFR Expression in Inflammatory and Non-Inflammatory Canine Mammary Carcinomas.

Inflammatory mammary carcinoma (IMC) is the most aggressive variant of invasive mammary tumours in dogs and in women. Decorin is an extracellular matrix molecule whose expression can be reduced or absent in various human cancers, which is associated with a poor prognosis. E-cadherin is a cell adhesion protein whose expression is reduced in several neoplasms. However, it is overexpressed in inflammatory breast cancers of women. EGFR is also associated with cancer development and is commonly overexpressed in aggressive neoplasms. This study aimed to characterise the expressions of Decorin, E-cadherin, and EGFR in canine inflammatory and non-inflammatory mammary carcinomas (IMC and non-IMC) and to evaluate their expression levels as prognostic indicators for survival and occurrence of metastases. Thirty-three IMC and 43 non-IMC cases were analysed retrospectively and submitted to immunohistochemical analysis. The reactions were quantified in five high-power field images from areas of the highest intensity and frequency of immunostaining (hot spots). We found significantly lower expression of Decorin and higher of E-cadherin and EGFR in canine IMCs. Patients with tumours that exhibited Decorin expression in less than 26.35% of epithelial cells had shorter survival (p = 0.0410) and a higher occurrence of distant metastases (p = 0.0115). E-cadherin is overexpressed in canine IMCs (p < 0.0001), similar to what occurs in women, reinforcing that dogs can be used as a study model for human IMC. EGFR overexpression in canine IMCs (p = 0.0322) provides evidence for potential targeted therapy with tyrosine kinase inhibitors.

P0560 Levels of disease-associated anti-integrin αVβ6 are substantially reduced after proctocolectomy in ulcerative colitis but persist in primary sclerosing cholangitis

Abstract Background Recently, autoantibodies directed against the epithelial adhesion protein integrin αVβ6 have been identified that strongly associate with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) with potential disease-driving effects. The presence of anti-αVβ6 in PSC without IBD is under debate. Moreover, data on the effect of proctocolectomy on autoantibody levels remains scarce. Methods Anti-αVβ6-directed autoantibodies were detected by a commercial enzyme-linked immunosorbent assay in patient sera, including healthy controls (N = 62), ulcerative colitis (N = 36), Crohn’s disease (CD, N = 65), PSC with concomitant IBD (78 samples from N = 41 patients), PSC without clinically manifest IBD (41 samples from N = 18 patients). Additionally, sera after proctocolectomy were studied (44 samples / N= 10 patients: 5 with UC, 5 with PSC). Immunofluorescent analyses of the target autoantigen were performed in liver, large bile ducts from surgical resections and colon tissue samples of PSC patients and single-cell RNA seq datasets were studied. Results The target autoantigen is expressed in disease-associated epithelia in the colon, in cholangiocytes in fibrotic portal fields and periductular glands of the large bile ducts as detected in immunofluorescence and single-cell RNA sequencing datasets. Anti-αVβ6 antibodies occur in 74% of patients with PSC with IBD, but also in 39% of patients with PSC without manifest IBD with lower levels. Anti-αVβ6 levels correlate with intestinal disease activity in patients with primary sclerosing cholangitis. Interestingly, proctocolectomy reduces autoantibody levels more strongly in UC than in PSC patients. Conclusion Disease-associated anti-integrin αVβ6 autoantibodies are also present in PSC without IBD with lower levels, assay sensitivity being a crucial determinant of detection. Moreover, proctocolectomy more strongly reduced autoantibody levels in UC than in PSC. Preferential autoantibody persistence in PSC after proctocolectomy might explain the increased incidence of chronic pouchitis in PSC.

High-Efficiency Electrochemiluminescence Biosensor with Antifouling and Antibacterial Functions for Sensitive and Accurate Analysis of Chloramphenicol in Seawater.

In marine environmental monitoring, due to the presence of a large number of interfering proteins and bacteria in seawater, it is of great significance to construct an efficient sensing interface with antifouling and antibacterial functions to avoid the aforementioned interferences. On this basis, the zwitterionic hydrogel based on sulfobetaine methacrylate (SBMA) and bovine serum albumin (BSA) was developed as an antifouling and antibacterial coating. The combination of hydration of zwitterions and hydrophilicity of hydrogels endows BSA@PSBMA with good antiadsorption ability, which effectively hinders the adhesion of proteins and bacteria, thereby improving the detection sensitivity of the biosensor. At the same time, the covalent grafting of SBMA and BSA solves the defect of poor stability of individual BSA in complex matrices, improving the stability and service life of the biosensor. In addition, Au@luminol was encapsulated in the zwitterionic hydrogel as an internal standard to realize a one-step integration of antifouling and ratio strategies, which simplifies the construction process of the biosensor. The developed electrochemiluminescence biosensor exhibited good sensitivity and accuracy for chloramphenicol detection, with a wide linear range of 1 pM to 100 nM and a low detection limit of 0.39 pM (S/N = 3), which is suitable for trace detection of antibiotics in seawater.

CRYβB2 alters cell adhesion to promote invasion in a triple-negative breast cancer cell line

ObjectiveAfrican American women with breast cancer experience disproportionately poor survival outcomes, primarily due to the high prevalence of the deadliest subtype; triple-negative breast cancer (TNBC). The CRYβB2 gene is upregulated in tumors from African American patients across all breast cancer subtypes, including TNBC, and is associated with worse survival rates. This study investigated the effect of CRYβB2 on the invasion of TNBC cells and the underlying mechanisms contributing to this phenotype.ResultsWe utilized the SUM159 cells with stable CRYβB2 overexpression in a 3D-culture tumor spheroids model in our investigation. A quantitative 3D invasion assay demonstrated that CRYβB2 overexpression significantly enhanced invasion (median invasion %; SUM159 = 0.14 and SUM159 + CRYβB2 = 0.33). RNA sequencing analysis indicated that CRYβB2 overexpression modulated cell-cell adhesion and extracellular matrix organization pathways, which are critical to invasion of cancer cells. Specifically, CRYβB2 suppressed the expression of key cell-cell adhesion genes known as clustered protocadherins and promoted the expression of PCDH7, a nonclustered protocadherin with known oncogenic roles in various cancers. Notably, the knockout of PCDH7 diminished the invasive capacity induced by CRYβB2 (median invasion %; SUM159 = 0.093, SUM159 + CRYβB2 = 0.184 and SUM159 + CRYβB2/PCDH7−/−=0.082). These findings provide a novel link between a previously identified differentially expressed gene, CRYβB2, in driving breast cancer phenotypes by modulating a class of adhesion proteins.

Control of biomedical nanoparticle distribution and drug release in vivo by complex particle design strategies.

The utilization of targeted nanoparticles as a selective drug delivery system is a powerful tool to increase the amount of active substance reaching the target site. This can increase therapeutic efficacy while reducing adverse drug effects. However, nanoparticles face several challenges: upon injection, the immediate adhesion of plasma proteins may mask targeting ligands, thereby diminishing the target cell selectivity. In addition, opsonization can lead to premature clearance and the widespread presence of receptors or enzymes limits the accuracy of target cell recognition. Nanoparticles may also suffer from endosomal entrapment, and controlled drug release can be hindered by premature burst release or insufficient particle retention at the target site. Various strategies have been developed to address these adverse events, such as the implementation of switchable particle properties, regulating the composition of the formed protein corona, or using click-chemistry based targeting approaches. This has resulted in increasingly complex particle designs, raising the question of whether this development actually improves the therapeutic efficacy in vivo. This review provides an overview of the challenges in targeted drug delivery and explores potential solutions described in the literature. Subsequently, appropriate strategies for the development of nanoparticular drug delivery concepts are discussed.

Prof. George Whitesides’ Contributions to Self-Assembled Monolayers (SAMs): Advancing Biointerface Science and Beyond

Prof. George Whitesides’ pioneering contributions to the field of self-assembled monolayers (SAMs) have profoundly influenced biointerface science and beyond. This review explores the development of SAMs as highly organized molecular structures, focusing on their role in advancing surface science, biointerface research, and biomedical applications. Prof. Whitesides’ systematic investigations into the effects of SAMs’ terminal group chemistries on protein adsorption and cell behavior culminated in formulating “Whitesides’ Rules”, which provide essential guidelines for designing bioinert surfaces. These principles have driven innovations in anti-fouling coatings for medical devices, diagnostics, and other biotechnological applications. We also discuss the critical role of interfacial water in SAM bioinertness, with studies demonstrating its function as a physical barrier preventing protein and cell adhesion. Furthermore, this review highlights how data science and machine learning have expanded the scope of SAM research, enabling predictive models for bioinert surface design. Remarkably, Whitesides’ Rules have proven applicable not only to SAMs but also to polymer-brush films, illustrating their broad relevance. Prof. Whitesides’ work provides a framework for interdisciplinary advancements in material science, bioengineering, and beyond. The enduring legacy of his contributions continues to inspire innovative approaches to addressing challenges in biomedicine and biotechnology.

Robust and Regular Micronano Binary Texture on the Complex Curved Surface for Enhanced Reendothelialization and Antithrombotic Performance.

Blood-contacting medical devices can easily trigger immune responses, leading to thrombosis and hyperblastosis. Constructing microtexture that provides efficient antithrombotic and rapid reendothelialization performance on complex curved surfaces remains a pressing challenge. In this work, we present a robust and regular micronano binary texture on the titanium surface, characterized by exceptional mechanical strength and precisely controlled wettability to achieve excellent hemocompatibility. Systematic in vitro and in vivo investigations confirmed that the micronano binary texture with superhydrophilic modification effectively suppressed the adhesion and activation of plasma proteins and blood cells, thereby mitigating the subsequent coagulation cascade and thrombosis. Meanwhile, the modified surface significantly upregulated the gene expression involving cell-matrix adhesion, growth factor synthesis, and calcium-mediated cytoskeleton remodeling and then accelerated the formation of a healthy and stable endothelial cell layer. This enhancement of re-endothelialization was not observed with pure titanium and superhydrophobic surfaces. Hence, superhydrophilic micronano binary texture not only significantly inhibits thrombosis but also selectively enhances the integrity and viability of the endothelial cell layer, making it a promising strategy for improving the long-term anticoagulation performance of vascular implants.