Developing redispersible nanocellulose products is crucial for their industrial applications. However, challenges persist in developing convenient and efficient processes. This study presents a green strategy using dynamic covalent chemistry to tune the hydrogen-bonding network of cellulose nanocrystals (CNCs). CNCs were combined with sodium lipoate (SL) in an aqueous solution and dried to form composite films. SL incorporation effectively prevents CNC aggregation via electrostatic repulsion and steric hindrance, transforming the CNC skeleton structure from a "bundle-to-bundle" structure to a uniform, horizontally stacked architecture. The composite films exhibited enhanced transparency, surface smoothness, and tunable mechanical properties. Upon water immersion, SL depolymerized and separated with 100% recovery. The remaining CNC skeleton readily redispersed into individual nanocrystals via sonication, achieving near-complete recovery even with 15% SL. This simple, water-based process tailors CNC film performance and enables complete closed-loop recycling, offering sustainability and simplicity for advanced applications.

Multivalent interactions mediated by multidomain proteins are pivotal in numerous biological processes. However, the thermodynamic intricacies of the domain interactions within such complexes remain elusive. In this study, we employed surface plasmon resonance to explore the temperature-dependent kinetics of multidomain protein interactions across various valences from monomers to tetramers. Rigorous screening of protein-peptide binding pairs fused with discrete multivalent protein scaffolds facilitated the selection of candidates with minimal nonspecific interactions and suitable monomer binding kinetics that could be extended to higher valences. We developed a theoretical model to extract the thermodynamic quantities for both inter- and intramolecular interactions. By employing initial rate analysis, we could extract thermodynamic quantities describing complicated interactions between multivalent proteins. Our analysis provides novel insights into the thermodynamics of intramolecular interactions in multivalent protein complexes with implications for protein design and engineering.

Biobased degradable polyesters have emerged as a promising alternative to mitigate plastic pollution and reduce dependence on petroleum resources. However, the utilization of tricyclic rigid diols derived from biomass remains limited, which restricts the overall performance of degradable polyesters. In this study, a novel diglycolicaldehyde xylose (DGX) diol containing a rigid tricyclic structure, synthesized from D-xylose and glyoxylic acid hydrate, is reported. Both the single- and multiple-stereoisomer forms of DGX were polymerized with linear diacids of varying carbon chain lengths to produce biobased poly(xylosediethylene alkylenedicarboxylate)s (PXAs) and m-PXAs polyesters. The high rigidity of the single-regioisomer DGX conferred enhanced thermal properties to PXAs, with a 5% weight loss temperature (Td,5%) reaching 372 °C and a glass transition temperature (Tg) of up to 93.8 °C. The structural regularity of the PXAs polymer backbone, combined with their higher molecular weights, resulted in a higher Tg relative to the m-PXAs analogues. Furthermore, the tricyclic unit endowed the polyesters with a superior gas barrier performance. Notably, the PXD film exhibited oxygen (O2) and carbon dioxide (CO2) barrier capabilities that were 3 and 7 times greater than those of polylactic acid (PLA), respectively. All amorphous polyesters allowed efficient recovery of DGX under mild conditions, with a yield of 93% achieved, and the recycled polymers displayed properties comparable to those of the virgin materials, thus demonstrating the potential for closed-loop recycling. This work presents a viable strategy for designing high-performance, sustainable biobased polyesters with end-of-life utility.

As a ubiquitous iron-storage protein, human heavy chain ferritin (FTH) is widely used in drug delivery. Recent advances in FTH engineering highlight the therapeutic and translational potential of glycosylation. We herein report the biosynthesis of various glycosylated FTHs (Glc-FTH, Glcn-FTH, and Gal-Glc-FTH) in Escherichia coli via enzymatic methods. Their self-assembly and thermal stability are unaffected by glycosylation, while the acid sensitivity is significantly enhanced, enabling depolymerization in a milder and more controllable manner. Gal-Glc-FTH exhibits exceptional advantages (low cytotoxicity, low immunogenicity, minimal apoptosis-inducing ability, prolonged half-life, and strong hepatic targeting), which collectively enhance its applications in hepatic targeted drug delivery. Although Glcn-FTH also significantly enhances hepatic targeting, its induction of high-titer antibodies indicates that it is more suitable for development as a vaccine carrier. Our findings emphasize the critical role of glycans in FTH properties, providing novel strategies and insights for cancer-targeted drug delivery systems.

DNA exhibits programmable self-assembly through complementary hydrogen bonding between nucleobases introduced to sugar-phosphate backbones in defined sequences, inspiring the development of synthetic analogs with nucleobases as recognition motifs. However, most nucleobase-containing polymers lack defined monomer sequences or molecular uniformity, limiting their biomimetic precision. In this work, we synthesized sequence-defined polymers bearing adenine and thymine units via a Passerini iterative exponential growth strategy. Butoxycarbonyl (Boc)-protected nucleobase-functionalized isocyanides were employed to construct poly(hydroxybutyrate) bearing butyl- and bp-thymine side chains and poly(hydroxybutyrate) with butyl- and bp-adenine side chains with uniform molecular weights. After Boc deprotection, NMR analyses revealed complementary adenine-thymine hydrogen bonding, showing characteristic downfield shifts in a 1:1 mixture, an association constant of 320 M-1 obtained by NMR titration, and thermoreversible behavior in variable-temperature NMR experiments. Furthermore, adenine and thymine were incorporated into a single polymer backbone, demonstrating the method's ability to encode programmable hydrogen-bonding motifs into uniform synthetic macromolecules.

The differences in the phospholipid profile between bacterial and mammalian membranes present a promising direction for designing antimicrobial peptides (AMPs). A key challenge, however, is engineering AMPs with a high affinity for bacterial anionic phospholipid (phosphatidylglycerol, PG) while minimizing off-target interactions with mammalian phosphatidylserine (PS). Herein, we report a multiarmed radially amphiphilic AMP (maRAP) design that enhances PG recognition, exhibiting potent antibacterial activity and exceptional antibacterial selectivity. Compared to the single-arm RAP (1aRAP), maRAPs exhibited superior affinity for PG, yet they exhibited negligible binding to PS. They also demonstrated significantly enhanced bactericidal efficacy and selectivity over 1aRAP in complex physiological environments. In the murine bladder-infection model, maRAPs more effectively reduced the bacterial load and attenuated infection-induced tissue damage, as demonstrated by an intact urothelial lining and minimal lamina propria edema at the infection site. This work presents the multiarm strategy as an effective approach for advanced AMP development.

In living cells,lipid bilayer membranes can be asymmetricallyfunctionalized with brush-like layers of macromolecules. Here, wedescribe a lipid membrane-initiated polymerization reaction for thegrowth of thick and dense polymer brushes directly from one side oflipid membranes. By incorporating a novel lipid-based polymerizationinitiator into lipid bilayers, we grew poly­(N-isopropylacrylamide)(PNIPAM) brushes from supported lipid bilayers (SLBs), small unilamellarvesicles (SUVs), and giant unilamellar vesicles (GUVs), via aqueousatom transfer radical polymerization (ATRP). We used quartz crystalmicrobalance with dissipation monitoring (QCM-D) and dynamic lightscattering (DLS) to quantify growth kinetics from SLBs and SUVs. Theresulting polymer brushes were up to 70 nm thick. Growth from GUVsled to the spontaneous transformation of spheroidal vesicles intodense, bush-like networks of “strings of pearls”. Broadlyspeaking, this approach could offer improved performance for biomedicalapplications and a valuable in vitro model for the biophysics of asymmetriclipid membranes.

Neuropeptide Y receptor Y1 (NPY1R) is an excellent potential target in glioma. This study aims to prepare 68Ga/211At-labeled NPY1R-targeting peptide as radiopharmaceuticals for glioma-targeted imaging and therapy. Molecular operating environment (MOE) was used for mutation scanning and design peptide sequences. The peptide KINWKFRLRY (KINW) showed low cytotoxicity and efficient tumor targeting. 68Ga-labeled KINW demonstrated the enhanced uptake in U87-MG cell xenograft models, confirming the potential imaging for glioma. KINW-conjugated N-succinimidyl-3-(trimethylstannyl) benzoate (m-MeATE) with 211At labeling (211At-ATE-KINW) exhibited a better stability and higher cellular than free 211At. 211At-ATE-KINW suppressed Akt/GSK3β/β-catenin signaling, reducing invasion, migration, and proliferation in U87-MG cells. Biodistribution revealed minimal normal tissue retention of 211At-ATE-KINW. Moreover, 211At-ATE-KINW had better tumor growth inhibition and significantly prolonged survival in U87-MG cell xenograft models compared to free 211At. Thus, a novel specific NPY1R peptide has potential to be applied in development of 68Ga/ 211At-labeled radiopharmaceuticals for glioma-targeted imaging and therapy.