Macromolecular Bioscience

Type 2 Diabetes Mellitus (T2D) is a chronic, obesity‐related, and inflammatory disorder characterize by insulin resistance, inadequate insulin secretion, hyperglycemia, and excessive glucagon secretion. Exendin‐4 (EX), a clinically established antidiabetic medication that acts as a glucagon‐like peptide‐1 receptor agonist, is effective in lowering glucose levels and stimulating insulin secretion while significantly reducing hunger. However, the requirement for multiple daily injections due to EX's short half‐life is a significant limitation in its clinical application, leading to high treatment costs and patient inconvenience. To address this issue, an injectable hydrogel system is developed that can provide sustained EX release at the injection site, reducing the need for daily injections. In this study, the electrospray technique is examine to form EX@CS nanospheres by electrostatic interaction between cationic chitosan (CS) and negatively charged EX. These nanospheres are uniformly dispersed in a pH‐temperature responsive pentablock copolymer, which forms micelles and undergoes sol‐to‐gel transition at physiological conditions. Following injection, the hydrogel gradually degraded, exhibiting excellent biocompatibility. The EX@CS nanospheres are subsequently released, maintaining therapeutic levels for over 72 h compared to free EX solution. The findings demonstrate that the pH‐temperature responsive hydrogel system containing EX@CS nanospheres can be a promising platform for the treatment of T2D.

We have investigated self‐association propensities of aqueous unfolded (U_AQ) forms of eight outer membrane proteins (OMPs), OmpA, OmpW, OmpX, PagP, OmpT, OmpLa, FadL, and Omp85. We found that high urea concentrations maintain all of these OMPs as monomers and that OmpA and OmpX remain monomeric upon dilution to 1 M urea. A pH screen showed that basic pH supports the least amount of U_AQ OMP self‐association, consistent with earlier studies showing that basic pH was optimal for better folding efficiencies. The addition of KCl increased U_AQ OMP self‐association, although the magnitudes of the responses were varied. These studies showed that urea can be used to tune the amount of U_AQ OMP self‐association and indicate that the presence of some urea may be useful in optimizing folding conditions because it diminishes aggregation.

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Summary: The application of different ionic liquids (IL), namely 1‐N‐butyl‐3‐methylimidazolium chloride ([C₄mim]⁺Cl⁻), 3‐methyl‐N‐butyl‐pyridinium chloride and benzyldimethyl(tetradecyl)ammonium chloride were investigated as solvents for cellulose. The ILs used have the ability to dissolve cellulose with a degree of polymerization in the range from 290 to 1 200 to a very high concentration. Using [C₄mim]⁺Cl⁻, no degradation of the polymer appears. By ¹³C NMR measurement it was confirmed that this IL is a so‐called non‐derivatizing solvent. [C₄mim]⁺Cl⁻ can be applied as a reaction medium for the synthesis of carboxymethyl cellulose and cellulose acetate. Without using any catalyst, cellulose derivatives with high degree of substitution could be prepared.

¹³C NMR spectrum of cellulose dissolved in the IL [C₄mim]⁺Cl⁻ (top). The ¹³C NMR spectrum of cellulose dissolved in DMSO/tetrabutylammonium fluoride trihydrate is shown for comparison (bottom).

Multivalent nanoparticle binding to cells can be of picomolar avidity making such interactions almost as intense as those seen with antibodies. However, reducing nanoparticle design exclusively to avidity optimization by the choice of ligand and its surface density does not sufficiently account for controlling and understanding cell–particle interactions. Cell uptake, for example, is of paramount significance for a plethora of biomedical applications and does not exclusively depend on the intensity of multivalency. In this study, it is shown that the mobility of ligands tethered to particle surfaces has a substantial impact on particle fate upon binding. Nanoparticles carrying angiotensin‐II tethered to highly mobile 5 kDa long poly(ethylene glycol) (PEG) chains separated by ligand‐free 2 kDa short PEG chains show a superior accumulation in angiotensin‐II receptor type 1 positive cells. In contrast, when ligand mobility is constrained by densely packing the nanoparticle surface with 5 kDa PEG chains only, cell uptake decreases by 50%. Remarkably, irrespective of ligand mobility and density both particle types have similar EC50 values in the 1–3 × 10⁻⁹ m range. These findings demonstrate that ligand mobility on the nanoparticle corona is an indispensable attribute to be considered in particle design to achieve optimal cell uptake via multivalent interactions.

Tóm tắt: Quá trình hòa tan nhanh cellulose trong dung dịch nước LiOH/urea và NaOH/urea đã được nghiên cứu một cách hệ thống. Hành vi hòa tan và khả năng hòa tan cellulose được đánh giá bằng cách sử dụng ¹³C NMR, kính hiển vi quang học, nhiễu xạ tia X góc rộng (WAXD), quang phổ FT-IR, phương pháp DSC và độ nhớt. Kết quả thí nghiệm cho thấy cellulose có trọng lượng phân tử trung bình độ nhớt ($\overline M _\eta $) là 11.4 × 104 và 37.2 × 104 lần lượt có thể được hòa tan trong 7% NaOH/12% urea và 4.2% LiOH/12% urea dung dịch nước làm lạnh trước tới −10 °C trong vòng 2 phút, trong khi tất cả chúng không thể hòa tan trong dung dịch nước KOH/urea. Khả năng hòa tan của các hệ dung môi giảm dần theo thứ tự LiOH/urea > NaOH/urea ≫ KOH/urea. Các kết quả từ DSC và ¹³C NMR chỉ ra rằng dung dịch nước LiOH/urea và NaOH/urea như là các dung môi không tạo dẫn xuất phá vỡ liên kết hydro bên trong và giữa các phân tử cellulose và ngăn chặn sự tiến gần đến nhau của các phân tử cellulose, dẫn đến sự phân tán tốt của cellulose để tạo thành dung dịch thực.

Shift hóa học ¹³C NMR của carbonyl carbon cho urea trong LiOH (a) và NaOH (b) của dung dịch cellulose.

Tóm tắt: Thuỷ phân alginate đang chứng tỏ có tính ứng dụng rộng rãi như là vật liệu sinh học. Chúng đã được sử dụng làm giá đỡ cho kỹ thuật mô học, phương tiện dẫn truyền thuốc, và mô hình một số chất nền ngoài tế bào cơ bản cho các nghiên cứu sinh học cơ bản. Những ứng dụng này đòi hỏi sự kiểm soát chặt chẽ của một số thuộc tính vật liệu bao gồm độ cứng cơ học, sự trương nở, sự phân hủy, sự gắn kết của tế bào, và sự liên kết hoặc giải phóng các phân tử hoạt tính sinh học. Kiểm soát các thuộc tính này có thể đạt được thông qua các sửa đổi hoá học hoặc lý học của chính chất polysaccharide hoặc các gel được hình thành từ alginate. Tính hữu ích của các gel alginate đã được sửa đổi này như là vật liệu sinh học đã được chứng minh qua nhiều nghiên cứu in vitro và in vivo.

Hình ảnh Micro‐CT của kết cấu giống xương dẫn xuất từ việc cấy ghép tế bào tạo xương trên gel mà phân hủy sau một khoảng thời gian nhiều tháng, dẫn đến sự sinh trưởng xương cải tiến.

Summary: Mesquite gum sourced from Prosopis velutina trees and gum arabic (Acacia spp.) were characterized using light scattering and Langmuir isotherms. Both gum materials were fractionated by hydrophobic interaction chromatography, yielding four fractions for both gums: FI, FIIa, FIIb and FIII in mesquite gum and FI, FII, FIIIa and FIIIb in gum arabic. In mesquite gum, the obtained fractions had different protein content (7.18–38.60 wt.‐%) and macromolecular dimensions ($\overline M _{\rm w}$ ≈ 3.89 × 10⁵–8.06 × 10⁵ g · mol⁻¹, R_G ≈ 48.83–71.11 nm, R_H ≈ 9.61–24.06 nm) and architecture given by the structure factor (R_G/R_H ratio ≈2.96–5.27). The mechanical properties of Langmuir monolayers at the air‐water interface were very different on each gum and their fractions. For mesquite gum, the most active species at the interface were those comprised in Fractions IIa and IIb and III, while Fraction I the π/A isotherm lied below that of the whole gum. In gum arabic only Fraction III developed greater surface pressure at the same surface per milligram of material than whole gum. This is rationalized in terms of structural differences in both materials. Mesquite gum tertiary structure seems to fit best with an elongated polydisperse macrocoil in agreement with the “twisted hairy rope” proposal for arabinogalactan proteoglycans.

Compression isotherms of gum arabic and mesquite gum.

Combined treatment is more effective than single treatment against most forms of cancer. In this work, doxorubicin loaded chitosan–W₁₈O₄₉ nanoparticles combined with the photothermal therapy and chemotherapy are fabricated through the electrostatic interaction between positively charged chitosan and negatively charged W₁₈O₄₉ nanoparticles. The in vitro and in vivo behaviors of these nanoparticles are examined by dynamic light scattering, transmission electron microscopy, cytotoxicity, near‐infrared fluorescence imaging, and tumor growth inhibition experiment. These nanoparticles have a mean size around 110 nm and show a pH sensitive drug release behavior. After irradiation by the 980 nm laser, these nanoparticles show more pronounced cytotoxicity against HeLa cells than that of free doxorubicin or photothermal therapy alone. The in vivo experiments confirm that their antitumor ability is significantly improved, resulting in superior efficiency in impeding tumor growth and extension of the lifetime of mice. image

Biominerals are characterised by unique morphologies, and it is a long‐term synthetic goal to reproduce these synthetically. We here apply a range of templating routes to investigate whether a fascinating category of biominerals, the single crystals with complex forms, can be produced using simple synthetic methods. Macroporous crystals with sponge‐like morphologies identical to that of sea urchin skeletal plates were produced on templating with a sponge‐like polymer membrane. Similarly, patterning of individual crystal faces was achieved from the micrometer to nanometer scale through crystallisation on colloidal particle monolayers and patterned polymer thin films. These experiments demonstrate the versatility of a templating approach to producing single crystals with unique morphologies.

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