Biomacromolecules最新文献

Recombinant elastin-like polypeptides (ELPs) have emerged as an attractive nanoplatform for drug delivery due to their tunable genetically encoded sequence, biocompatibility, and stimuli-responsive self-assembly behaviors. Here, we designed and biosynthesized an HER2 (human epidermal growth factor receptor 2)-targeted affibody-ELP fusion protein (Z-ELP), which was subsequently conjugated with monomethyl auristatin E (MMAE) to build a protein-drug conjugate (Z-ELP-M). Due to its thermal response, Z-ELP-M can immediately self-assemble into a nanomicelle at physiological temperature. Benefiting from its active targeting and nanomorphology, Z-ELP-M exhibits enhanced cellular internalization and deep tumor penetration in vitro. Moreover, Z-ELP-M shows excellent tumor targeting and superior antitumor efficacy in HER2-positive ovarian cancer, demonstrating a relative tumor growth inhibition of 104.6%. These findings suggest that an affibody-functionalized elastin-like peptide-drug conjugate nanomicelle is an efficient strategy to improve antitumor efficacy and biosafety in cancer therapy.

The use of biopolymers as an alternative to petroleum-based polymers offers a sustainable solution with benefits such as biodegradability and unique functionalities. In this study, starch/zein bioparticles (BPs) obtained by nanoprecipitation were employed to synthesize acrylic polymer/biopolymer waterborne nanoparticles with excellent film formation capability. These hybrid nanoparticle dispersions were obtained through a semibatch emulsion polymerization using the previously synthesized BPs as seed and variable monomeric formulations composed of butyl acrylate and methyl methacrylate. A synergetic effect between acrylic and biopolymer phases was evidenced where the incorporation of BPs had a fundamental role in improving sensitive properties, such as film blocking resistance, while attaining smooth films at room temperature. These excellent film-forming properties of starch/acrylic hybrid latexes without requiring the addition of formulation agents, which depict an important benefit from an environmental viewpoint, demonstrate that they represent a promising alternative for the development of a new generation of eco-friendly binders.

Aerogels exhibit poor adhesion to wet tissue surfaces, which is a significant factor that limits their hemostatic properties. In this work, we propose a new method for investigating aerogel hemostatic materials by introducing the concept of the 'rapid tissue hydration layer-triggered property' into the hemostatic material. A chitosan derivative (Csde) with a "swollen property" was prepared via an amide reaction, followed by the incorporation of the extracted bletilla striata complex (Bscai) into the chitosan derivative to fabricate the Bscai/Csde hemostatic material. The research results indicated that the Bscai/Csde hemostatic material exhibited a rapid tissue hydration layer-triggered response, outstanding hemostasis ability, as well as excellent hemocompatibility, antibacterial properties, and cytocompatibility. Additionally, the preparation method for the Bscai/Csde hemostatic material is straightforward, and the raw materials are readily available. Therefore, this study presents a novel method for developing a hemostatic material method, and the composite aerogel hemostatic material demonstrates considerable potential for future applications.

Here, we demonstrate that the spatial distribution of lipophilic cations governs the complexation pathways, serum stability, and biological performance of polymer-pDNA complexes (polyplexes). Previous research focused on block/statistical copolymers, whereas gradient copolymers, where the density of lipophilic cations diminishes (gradually or steeply) along polymer backbones, remain underexplored. We engineered gradient copolymers that combine the polyplex colloidal stability of block copolymers with the transfection efficiency of statistical copolymers. We synthesized length- and compositionally equivalent gradient copolymers (G1-G3) along with statistical (S) and block (B) copolymers of 2-(diisopropylamino)ethyl methacrylate and 2-hydroxyethyl methacrylate. We mapped how polymer microstructure governs pDNA loading per polyplex, pDNA conformational changes, and polymer-pDNA binding thermodynamics via static light scattering, circular dichroism spectroscopy, and isothermal titration calorimetry, respectively. While gradient steepness is a powerful design handle to improve polyplex physical properties, augment pDNA delivery capacity, and attenuate polycation-triggered hemolysis, microstructural contrasts did not elicit differences in complement activation.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, poses a heightened colorectal cancer risk due to persistent mucosal inflammation and barrier dysfunction. In this article, a negatively charged thermosensitive hydrogel loaded with pectin microspheres was used as the enema for UC treatment. Succinic acid was immobilized on poly(ε-caprolactone-co-glycolide)-poly(ethylene glycol)-poly(ε-caprolactone-co-glycolide) (PCLGA-PEG-PCLGA) triblock copolymers to preferentially coat on cationic-inflamed sites via electrostatic interaction for reconstructing the mucosal barrier. Anti-inflammation drug 5-aminosalicylic acid (5-ASA) and curcumin-loaded pectin microspheres (Pec@Cur) were dispersed in the hydrogel for the inflammatory treatment of UC. The thermally sensitive hydrogels were rectally injected into UC model mice. The hydrogel effectively adhered to ulcers and prolonged colon retention, enabling sustained drug release and remarkably relieving the symptoms of colitis. The negatively charged hydrogel exhibited excellent significance in the UC treatment.

Bacterial cellulose (BC) has a long-standing human consumption history in different geographies without any report of adverse effects. Despite its unique textural and functional properties, the use of BC in food products in Europe is still restricted due to concerns over its nanosize. Here, we evaluated the potential uptake of celluloses (from plant and microbial sources, processed using different blenders) by macrophages (differentiated THP-1 cells) and human intestinal epithelial cells (Caco-2 and HT29-MTX cells) without (coculture) or with (triculture) Raji-B cells. A carbohydrate-binding module coupled to a green fluorescent protein was employed to observe cellulose in the cell cultures by confocal laser scanning microscopy and stimulated emission depletion microscopy. The methodology demonstrated excellent sensitivity, allowing detection of single nanocrystals within cells. All celluloses were taken up by the macrophages, without significantly compromising the cell's metabolic viability. The viability of the cocultures was also not affected. Furthermore, no internalization was observed in the triculture cell model that was exposed 24 h to BC and Avicel LM310. When (rarely) detected, cellulose particles were found on the apical side of the membrane. Overall, the obtained results suggest that BC should not be absorbed into the human gut.

Fibrotic changes in pediatric clubfoot provide an opportunity to improve corrective therapy and prevent relapses with targeted drugs. This study defines the parameters of clubfoot fibrosis and presents a unique analysis of a simple pseudo-3D in vitro model for disease-specific high-throughput drug screening experiments. The model combines clubfoot-derived fibroblasts with a biomimetic cultivation environment induced by the water-soluble polymers Ficoll and Polyvinylpyrrolidone, utilizing the principle of macromolecular crowding. We achieved higher conversion of soluble collagen into insoluble collagen, accelerated formation of the extracellular matrix layer and upregulated fibrosis-related genes in the mixed Ficoll environment. To test the model, we evaluated the effect of a potential antifibrotic drug, minoxidil, emphasizing collagen content and cross-linking. While the model amplified overall collagen deposition, minoxidil effectively blocked the expression of lysyl hydroxylases, which are responsible for the increased occurrence of specific collagen cross-linking in various fibrotic tissues. This limited the formation of collagen cross-link in both the model and control environments. Our findings provide a tool for expanding preclinical research for clubfoot and similar fibroproliferative conditions.

Peptide-based hydrogels are of interest to biomedical applications. Herein, we have explored the introduction of fluorinated amino acids in hydrogelator H-FQFQFK-NH₂ (P1) to design a series of fluorinated peptide hydrogels and evaluate the in vitro and in vivo properties of the most promising analogues. The impact of fluorinated groups on peptide gelation, secondary structure, and self-assembly processes was assessed. We show that fluorine can significantly improve hydrogel stiffness, compared to the nonfluorinated reference P1. For P15 (H-FQFQF(o-CF₃)K-NH₂), P18 (H-FQFQF(F₅)K-NH₂), and P19 (H-FQFQM(CF₃)K-NH₂), microscopy studies scrutinized fiber morphologies and alignment in the network. In vitro release studies of hydrogels loaded with an opioid cargo suggested improved hydrogel stability for P15 and P18. This improved stability was further validated in vivo, notably for P15, giving the most significant increased gel residence time, with more than 20% of hydrogel still present 9 days post-injection, as monitored by nuclear SPECT-CT imaging.

Paediatric acute myeloid leukemia (AML) is a heterogeneous hematological malignancy still heavily reliant on traditional chemotherapeutic approaches. Combination treatments have shown to be a superior approach, but their success is often hindered by side effects and different drugs' pharmacokinetics. Here, we investigated ABT-737 and Purvalanol A as a potential drug pairing for pediatric AML and described the development of CD33-targeted polymeric nanoparticles (NPs) to enable their simultaneous targeted codelivery. Separate drug encapsulation within poly(lactic-co-glycolic acid) (PLGA) NPs was optimized prior to coencapsulation of both drugs at a synergistic ratio in PEGylated PLGA NPs. The therapeutic effects of formulations were evaluated in a panel of pediatric AML cells, and dual drug-loaded NPs (dual NPs) demonstrated significantly enhanced apoptotic cell death. Moreover, conjugation to gemtuzumab resulted in improved NP binding and internalization in CD33-positive cells. Finally, CD33-targeted dual-loaded NPs showed enhanced cytotoxicity to CD33-positive AML cells via CD33-mediated targeted drug delivery.

The legislature determines the recycled and waste contents in fabrication processes to ensure more sustainable production. PLA's mechanical recycling and reuse are limited due to the performance decrease caused by thermal or hydrolytic instability. Our concept introduces an upcycling route involving PLA depolymerization using propylene glycol as a reactant, followed by the methacrylation, assuring the liquid systems' curability provided by radical polymerization. PLA-containing curable systems were studied from a rheological and thermomechanical viewpoint. The viscosity levels varied from 33 to 3911 mPa·s at 30 °C, giving a wide capability potential. The best system reached 2240 MPa storage modulus, 164.1 °C glass-transition temperature, and 145.6 °C heat-resistant index, competitive values to commercial systems. The printability was verified for all of the systems. Eventually, our concept led to SLA resin production containing PLA waste content up to 51 wt %.