Capsules have hollow cores and closed wall structures, and they have attracted considerable interest due to their wide applications and significance in life science. The engineering process of ...bioinspired capsules and related applications have earned heavy concerns. However, the mechanism of capsule formation is often ignored. Herein, based on polyornithine (POR) and tannic acid (TA), two facile strategies to engineer bioinspired capsules were proposed, and the formation mechanisms were deeply explored. We found that the oxidized state of TA had a profound influence not on the thickness or permeability of the formed capsule but on the mechanism and generation process. Compared to TA/POR capsules produced from TA without oxidization (TA/POR), capsules produced from TA with preoxidization (oTA/POR) had thicker shells with higher impermeability. The dominant construction mode in the shells of TA/POR capsules was electrostatic interactions but became Schiff base bonds in oTA/POR capsules. The permeability of oTA/POR displayed pH reversibility and strong pH dependence, with 100% permeability at lower pH and 100% impermeability at pH 7, completing loading/releasing kinetics in minutes at pH 4. We believe these findings contribute to knowledge of bioinspired capsules from engineering processes and formation mechanisms, extending their applications in various fields, such as in drug delivery, artificial cells, and sensors.
Display omitted
•Bioinspired capsules were engineered through a facile process.•The oxidation state of tannic acid had an influence on the mechanism of capsule.•The capsules based on tannic acid were constructed by electrostatic interactions.•The capsules based on oxidated tannic acid were rich in Schiff base bonds.•The permeability of capsules displayed pH reversibility and strong pH dependence.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recent genetic studies for osteoarthritis (OA) have been focused on ASPN, the gene encoding asporin, where aspartic acid (D)-repeat polymorphisms are associated with OA in several ethnic groups. The ...purpose of the present study is to further examine the association of the D-repeat polymorphism in a Han Chinese population. The D-repeat polymorphism was genotyped in 354 knee OA patients (257 women and 97 men) who suffered from primary symptomatic knee OA with radiographic confirmation, and the association of the repeat with various clinical parameters was examined. The age at onset (years) in patients with the D14 allele (mean: 51.9, SD: 8.5) was younger than that those without the D14 allele (mean: 54.9, SD: 10.9) (P = 0.023). Survival analysis showed D14 was significantly associated with age at onset of OA (P = 0.004 in the dominant model). The average age at onset of patients with the D13/D13 genotype (mean: 56.1, SD: 11.1) was older than those without the D13/D13 genotype (mean: 53.0, SD: 9.9) (P = 0.013). Our study further highlighted the significance of asporin in OA.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Display omitted
It is of considerable interest to construct an ideal drug delivery system (i.e., high drug payload, minimal cytotoxicity, rapid endocytosis, and lysosomal escape) under mild ...conditions for disease treatment, tissue engineering, bioimaging, etc. Inspired by the coordinative interactions between histidine and metal ions, we present the facile synthesis of hexahistidine (His6)-metal assembly (HmA) particles under mild conditions for the first time. The HmA particles presented a high loading capacity, a wide variety of loadable drugs, minimal cytotoxicity, quick internalization, the ability to bypass the lysosomes, and rapid intracellular drug release. In addition, HmA encapsulation largely improved the antitumor ability of camptothecin (CPT) relative to free CPT. By capitalizing on these promising features in drug delivery, HmA will have great potential in various biomedical fields.
It is of considerable interest to construct an ideal drug delivery system (i.e., high drug payload, minimal cytotoxicity, rapid endocytosis, and lysosomal escape) under mild conditions. Inspired by the coordinative interactions between histidine and metal ions, we present for the first time the facile synthesis of Hexahistidine (His6)-metal assembly (HmA) particles under mild conditions. The HmA particles exhibited a high loading capacity, a wide variety of loadable drugs, minimal cytotoxicity, quick internalization, the ability to bypass the lysosomes, and rapid intracellular drug release. By capitalizing on these promising features in drug delivery, HmA will have great potential in various biomedical fields.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Proteins are considered to be one of the most important highly reproducible and monodisperse building blocks with specific functions in life sciences and material science. Protein capsules and their ...hybrids composed of protein–polymer conjugates have been intensively explored in drug delivery, catalysis, and cell-mimicking functions. Herein, we present a facile, universal, and efficient method to fabricate the diverse protein capsules, independent of the molecular weight (M w), isoelectric points (IEP), wettability, amino acid sequence, and functional domains of enumerated proteins. The protein capsules were well characterized by various techniques. Furthermore, their ability to store the original protein functionality was demonstrated, which was mainly embodied in their enzyme responsiveness and good biocompatibility in vitro and in vivo. We believe that these protein capsules have multiple potential applications such as in drug delivery, tissue engineering, catalysis, and other application fields.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Age‐related diseases are among the leading causes of morbidity worldwide currently. Therefore, there is an urgent need to develop effective interventions to reduce aging. In mice, the selective ...elimination of senescent cells via senolytics extends the median lifespan and attenuates various age‐related diseases including osteoarthritis (OA). However, most classified senolytics may also affect non‐senescent cells because of their suboptimal specificity for senescent cells, which hampers the translation of senolytic therapies to human diseases. Precise targeting of senolytics to specific senescent cell types may help circumvent these potential hurdles. In the joints of OA, abundant senescent fibroblast‐like synoviocytes (FLSs) are observed in the synovium region, which can promote the degradation of chondrocytes. Here, an aptamer‐functionalized liposome (LS) is developed, which encapsulates with senolytics (dasatinib and quercetin, DQ), termed as CX3‐LS‐DQ. This CX3‐LS‐DQ exhibits high affinity for FLS, a reasonably long circulation time, minimal toxicity, and strong clearance ability in senescent FLS. In the OA mouse model, intra‐articular injection of CX3‐LS‐DQ effectively attenuates cartilage degradation in vivo. Overall, the FLS‐specific aptamer‐functionalized drug delivery system could act as a novel carrier for targeted drug delivery to the synovium, providing a foundation for potential clinical translation in OA therapy.
Senescent FLSs are increased and can promote chondrocyte degradation during osteoarthritis progression. Aptamer CX3, screened by the cell‐SELEX system, exhibits a remarkable ability to distinguish FLS from chondrocytes. Intra‐articular injection of CX3‐modified liposomes can induce the apoptosis of senescent FLS and suppress the progression of osteoarthritis, providing a potential strategy for osteoarthritis therapy in the clinic.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The accumulation of senescent cells in bone during aging contributes to senile osteoporosis, and clearance of senescent cells by senolytics could effectively alleviate bone loss. However, the ...applications of senolytics are limited due to their potential toxicities. Herein, small extracellular vesicles (sEVs) have been modified by incorporating bone‐targeting peptide, specifically (AspSerSer)6, to encapsulate galactose‐modified Maytansinoids (DM1). These modified vesicles are referred to as (AspSerSer)6‐sEVs/DM1‐Gal, and they have been designed to specifically clear the senescent osteocytes in bone tissue. In addition, the elevated activity of lysosomal β‐galactosidase in senescent osteocytes, but not normal cells in bone tissue, could break down DM1‐Gal to release free DM1 for selective elimination of senescent osteocytes. Mechanically, DM1 could disrupt tubulin polymerization, subsequently inducing senescent osteocytes apoptosis. Further, administration of bone‐targeting senolytics to aged mice could alleviate aged‐related bone loss without non‐obvious toxicity. Overall, this bone‐targeting senolytics could act as a novel candidate for specific clearance of senescent osteocytes, ameliorating age‐related bone loss, with a promising therapeutic potential for senile osteoporosis.
Herein, small extracellular vesicles (sEVs) have been modified by incorporating bone‐targeting peptide, specifically (AspSerSer)6, to encapsulate galactose‐modified Maytansinoids (DM1). These modified vesicles are referred to as (AspSerSer)6‐sEVs/DM1‐Gal, and they have been designed to specifically clear the senescent osteocytes in bone tissue to treat senile osteoporosis.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A genetic association of knee osteoarthritis (OA) and a C/T transition single nucleotide polymorphism (SNP) (rs912428) located in intron 1 of the LRCH1 gene has recently been reported in European ...Caucasians; however, the results are inconsistent. Our objective was to evaluate the association in different knee OA populations. Three case-control association studies were conducted in Han Chinese, Japanese, and Greek Caucasian populations. The LRCH1 SNP was genotyped in patients who had primary symptomatic knee OA with radiographic confirmation and in matched controls, and the association was examined. We performed a meta-analysis for the studies together with results of two previous papers using the DerSimonian-Laird procedure and calculated the power of the pooled studies by the software R. A total of 1,145 OA patients and 1,266 controls were genotyped. No significant difference was detected in genotype or allele frequencies between knee OA and control groups in the three populations (all P > 0.05). Association was not observed even after stratification by gender and Kellgren/Lawrence (K/L) scores. Meta-analysis also supported the lack of association between LRCH1 and knee OA. The strong heterogeneity between original and replication studies was detected in Caucasian populations. However, a tendency for the increase of TT genotype was observed in the European populations (OR = 1.46, P = 0.06). The powers for European and Asian replication studies were less than 0.8. Our results suggest that there is no association between LRCH1 and knee OA. However, lack of association should be concluded by further replication studies.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
CALM1 gene encodes calmodulin (CaM), an important and ubiquitous eukaryotic Ca2+-binding protein. Several studies have indicated that a deficient CaM function is likely to be involved in the ...pathogenesis of osteoarthritis (OA). Using a convincing genome-wide association study, a Japanese group has recently demonstrated a genetic association between the CALM1 core promoter polymorphism (-16C/T transition SNP, rs12885713) and OA susceptibility. However, the subsequent association studies failed to provide consistent results in OA patients of differently selected populations. The present study is to evaluate the association of the -16C/T polymorphism with knee OA in a Chinese Han population.
A case-control association study was conducted. The polymorphism was genotyped in 183 patients who had primary symptomatic knee OA with radiographic confirmation and in 210 matched controls. Allelic and genotypic frequencies were compared between patients and control subjects.
No significant difference was detected in genotype or allele distribution between knee OA and control groups (all P > 0.05). The association was also negative even after stratification by sex. Furthermore, no association between the -16C/T SNP genotype and the clinical variables age, sex, BMI (body mass index) and K/L (Kellgren/Lawrence) score was observed in OA patients.
The present study suggests that the CALM1 core promoter polymorphism -16C/T is not a risk factor for knee OA susceptibility in the Chinese Han population. Further studies are needed to give a global view of this polymorphism in pathogenesis of OA.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Microcapsules are one of the most promising microscale drug carriers due to their facile fabrication, excellent deformability, and high efficacy in drug storage and delivery. Understanding the ...effects of their physicochemical properties (size, shape, rigidity, charge, surface chemistry,
etc.
) on both
in vitro
and
in vivo
performance is not only highly significant and interesting but also very challenging. Stiffness, an important design parameter, has been extensively explored in recent years, but how the rigidity of particles influences cellular internalization and uptake mechanisms remains controversial. Here, one-layered lysozyme-based microcapsules with well-controlled stiffness (modulus ranging from 3.49 ± 0.18 MPa to 26.14 ± 1.09 MPa) were prepared and used to investigate the effect of stiffness on the uptake process in dendritic cells and the underlying mechanism. The cellular uptake process and endocytic mechanism were investigated with laser scanning confocal microscopy, mechanism inhibitors, and pathway-specific antibody staining. Our data demonstrated that the stiffness of protein-based microcapsules could be a strong regulator of intracellular uptake and endocytic kinetics but had no obvious effect on the endocytic mechanism. We believe our results will provide a basic understanding of the intracellular uptake process of microcapsules and the endocytic mechanism and inspire strategies for the further design of potential drug delivery microcarriers.
One-layered lysozyme-based microcapsules with well-controlled stiffness were used to investigate the stiffness effect on the cellular uptake and endocytic mechanism in dendritic cells.
Restoring protein functions or supplying proteins is considered one of the most powerful therapeutic strategies for many diseases, but it is mainly limited by the denaturation of proteins during ...encapsulation and degradation by proteases during in vivo delivery, and limits its delivery. Herein, by encapsulating a protein (catalase, an enzyme) in a hexahistidine-metal assembly (HmA) via a de novo strategy under mild conditions, we demonstrated that HmA could maintain the bioactivity of the enzyme, protect the enzyme from proteinase degradation, and deliver the encapsulated protein for the prevention of disease in an acute liver injury model.
PDF
