Biomacromolecules最新文献

Fluorescent polymeric thermometers, despite their noninvasive detection and rapid response for intracellular temperature monitoring, face challenges in achieving excellent biocompatibility and high sensitivity. Herein, we synthesized a water-soluble unconventional temperature-sensitive fluorescent polymer (P2) through terminally grafting poly(N-vinylcaprolactam) (PNVCL) onto hyperbranched polyborosiloxane (P1). The P2 exhibited efficient red-light emission and good photostability. Particularly, when the temperature rises, the PNVCL units transform from hydrophilic to hydrophobic, resulting in the dislocation of local segments of P2, suppressing radiative transitions and simultaneously weakening its through-space conjugation, further reducing its fluorescence intensity, and endowing the P2 with a high temperature-sensing sensitivity of 10.06% °C^-1. Finally, the real-time monitoring of intracellular temperature variation was further conducted. This work not only develops promising thermochromic materials for intracellular temperature sensing but also provides further insight into the temperature-sensing mechanism of unconventional fluorescent polymers.

G-quadruplexes are noncanonical DNA structures rather ubiquitous in the human genome, which are thought to play a crucial role in the development of the majority of cancers. Here, we present a novel coarse-grained approach in modeling G-quadruplexes that accounts for their structural flexibility. We apply it to study the polymeric properties of G-quadruplex multimers, with and without crowder molecules, to mimic in vivo conditions. We find that, contrary to some suggestions found in the literature, long G-quadruplex multimers are rather flexible polymeric macromolecules, with a local persistence length comparable to monomer size, exhibiting a chain stiffness variation profile consistent with a real polymer in good solvent. Moreover, in a crowded environment (up to 10% volume fraction), we report that G-quadruplex multimers exhibit an increased propensity for coiling, with a corresponding decrease in the measured chain stiffness.

We have synthesized hybrid membranes composed of amphiphilic block copolymers, polybutadiene-poly(ethylene oxide) [PBd-b-PEO], with different lengths [PBd₂₂-PEO₁₄ and PBd₁₁-PEO₈] and mixtures of phospholipids (DOPC:DOPG:DOPE 50:25:25 mol %) to combine the properties of both in terms of stability and fluidity of the membrane. The amphiphilic block copolymers increase the stability, whereas the lipids support the functionality of membrane proteins. The hybrid nature of the bilayers was studied by means of Cryo-TEM, Langmuir-Blodgett technique, atomic force microscopy (AFM), electrical measurements, and fluorescence-based stopped-flow assay to determine the permeability of the membrane for water and osmolytes. We observe that the structural, thermodynamic, and permeability properties of hybrid PBd₁₁-PEO₈ membranes are similar to their purely lipid counterparts, with the advantage of being more stable and resisting a higher transmembrane electrical potential. Hybrid membranes with the longer polymer, PBd₂₂-PEO₁₄, display more significant structural, thermodynamic, and permeability differences and show less favorable properties than hybrid-PBd₁₁-PEO₈ membranes.

Combinatorial cancer therapy benefits from injectable hydrogels for localized, controlled drug delivery. This study presents a thiol-ene conjugated hydrogel formed by cross-linking thiol-modified hyaluronic acid (HASH) with vinyl sulfone-modified β-cyclodextrin (CDVS). Four formulations (23Gel-16, 23Gel-33, 99Gel-16, 99Gel-33) were synthesized by varying HASH molecular weight (23 or 99 kDa) and CDVS modification (16% or 33%). Rheological analysis confirmed enhanced viscoelasticity with increasing molecular weight and modification (99Gel-33 > 99Gel-16 > 23Gel-33 > 23Gel-16). The system enabled combinatorial delivery of doxorubicin (DOX) and carvacrol (CRV), exhibiting tumor-responsive degradation and tunable release. DOX release accelerated under tumor-mimicking conditions (100% in 46 h vs 58.7% in PBS), while CRV showed an initial burst followed by sustained release. The hydrogel promoted mesenchymal stem cell proliferation and effectively inhibited triple-negative breast cancer cells. This injectable, tumor-responsive hydrogel system offers a promising platform for minimally invasive, personalized cancer therapy.

Photodynamic therapy (PDT) has emerged as a promising modality for cancer treatment, but its clinical application is constrained by unexpected phototoxicity arising from nonspecific photosensitizer activation and their "always-on" nature. Herein, we developed a switchable nanophotosensitizer, poly(cation-π) nanoparticles (NP), which achieves supramolecular assembly through cation-π interactions. By coupling choline cationic moieties with aromatic photosensitizers (ZnPc), the polymer facilitates self-assembly driven by cation-π interactions for NP engineering. Surprisingly, the photoactivity of ZnPc was completely quenched upon complexation via cation-π interactions, thereby significantly avoiding skin phototoxicity. Upon targeting tumor cells, NP undergoes a GSH-responsive degradation process that weakens cation-π interactions, leading to spontaneous restoration of photoactivity and amplifying tumor immunogenic pyroptosis. In vivo studies demonstrated that NP achieved a high tumor inhibition rate of 84% while effectively avoiding skin phototoxicity. This work provides a novel perspective for enhancing the safety and efficacy of PDT-based tumor treatment.

This work reports the development and evaluation of dendrimer-based nanogels based on polyamidoamine (PAMAM) dendrimer generation 5, engineered to act as a carrier with reactive oxygen species (ROS)-scavenging capabilities. We developed a cross-linking reaction-enabled flash nanoprecipitation method in which the cross-linking reaction occurs during the flash nanoprecipitation process to form a cross-linked nanostructure. Using this approach, an N-hydroxysuccinimide (NHS)-functionalized ROS-responsive thioketal cross-linker (TK-NHS) was synthesized and utilized to cross-link DAB-core PAMAM dendrimer G5, resulting in the formation of G5-TK nanogels. The resulting nanogels were characterized using dynamic light scattering and transmission electron microscopy, and their cytocompatibility, irritancy, cellular uptake, and ROS scavenging activity were assessed. We confirmed the ROS scavenging capability of these nanogels and observed favorable safety profiles. The G5-TK nanogels can be further developed as carriers for therapeutic delivery applications to treat oxidative stress-related pathological conditions.

Block polymers present an almost endless realm of possibilities to develop functional materials for myriad applications. The established self-assembly of block polymers allows researchers to access properties that are inaccessible in homopolymers. However, there is a need to develop more sustainable options than the current commodity block polymers. Derived from renewable resources and industrially compostable, poly(lactide) (PLA) is at the forefront of technological advancements in sustainable block polymers. Its material properties including high stiffness, relatively high glass transition temperature, and semicrystallinity in isotactic versions lend themselves to many applications, and its ease of synthesis provides a well-established platform for developing high-performance materials. This Perspective highlights recent advancements associated with PLA-containing block polymers, including their syntheses, mesostructural considerations, and mechanical properties, from resilient elastomers to tough plastics. We also give our perspective on the subfield of PLA block polymers, our outlook on the future, and our assessment of exciting developments yet to come.

Antibodies are vital biologic therapeutics, but their impact is limited by thermal instability. This requires maintaining a cold chain, from the point of manufacture to the point of use. We report an approach that could reduce the need for a cold chain. We present a thermal protectant (TP) for immunoglobulin G (IgG) that mimics the behavior of the heat shock protein HSP60. This hydrogel copolymer nanoparticle shows minimal affinity for IgG at or below 25 °C. As temperatures rise and approach the proteins melting temperature (T_m), the TP undergoes an autonomous phase transition (∼27 °C), above which the TP shows high affinity for IgG sequestering and stabilizing IgG at temperatures far above T_m. As temperatures return to RT, the TP reverts to its water-swollen state, allowing any metastable proteins time to refold to their native state before being released. The optimized TP has very low IgG molar capacity, effectively isolating and preventing aggregation at elevated temperatures.

Modern wearable sensors for health monitoring are becoming increasingly popular due to their versatility. This study investigates the effects of Co²⁺ ions in flexible alginate-based composite films with doped cobalt and poly(3,4-ethylene-dioxythiophene):polystyrenesulfonate (PEDOT:PSS) for respiratory health monitoring. Contrary to expectations, the Co²⁺-doped Na-Alg/PEDOT:PSS/Glycerol 3b nanocomposite showed lower LED intensity (168 ± 75 au) and conductivity (5.04 × 10^-5 S/m). The addition of Co²⁺ ions negatively affected the electrical performance and hindered the charge mobility and structural integrity. In contrast, the Na-Alg/PEDOT:PSS/glycerol 2b film achieved higher LED intensity (236 ± 25 au) and maximum conductivity (6.61 × 10^-5 S/m), which can be attributed to the plasticizing effect of glycerol that improves the homogeneity of the film and charge transport. This composite also shows excellent wearability on the skin, pressure sensitivity, and the ability to monitor respiration.

The growing threat of antibiotic resistance highlights the urgent need for new antimicrobial agents. Nonribosomal peptides (NRPs) are potent antibiotics with complex structures, but generating novel NRP analogues is costly and inefficient. An emerging alternative is using ribosomally synthesized and post-translationally modified peptides (RiPPs), which are gene-encoded, allowing for easier mutagenesis and modification. This study aimed to produce peptides with two key structural elements of many NRP antibiotics: a macrocycle and an N-terminal lipid moiety. The RiPP enzymes SyncM and PirF were employed-SyncM introduced lanthionine or methyllanthionine macrocycles, while PirF incorporated isoprenyl chains to emulate the lipid moieties in NRPs. Both enzymes successfully modified the templates, and their combined use generated lipidated macrocyclic peptides, resembling lipopeptide antibiotics. These findings demonstrate the potential of SyncM and PirF as versatile tools for designing novel gene-encoded NRP mimics, enabling high-throughput screening for new bioactive peptides.