Wound closure by suture and staple demands surgical skills and carries risks of traumatic complications, whereas current tissue adhesives exhibit insufficient wet adhesion strength, unsatisfactory in vivo biodegradability, and durability. Inspired by the robust underwater adhesion of mussels, whose underwater adhesion derives from the synergy of hydrophobic and adhesive matrix, a tough bioadhesive (PLD) was developed by coassembly of lipoic acid (LA) and a dopamine-functionalized lipoic acid derivative (LAD). Mimicking the mussel's adhesion mechanism, PLD expelled interfacial water via hydrophobic chains, enabling catechol and carboxyl groups to form robust bonds with wet tissue. It exhibited water-strengthened underwater adhesion (approximately from 37.06 to 50.23 kPa after 180 min water immersion) due to water-activated aggregation of hydrophobic chains. Owing to the combined effect of hydrogen bonds, π-π interaction, and hydrophobic associations, PLD displayed durable wet adhesion because it had exceptional antiswelling properties with a remarkably low swelling ratio of 2.07% after 72 h in a physiological environment. In addition, it was bioresorbable, cytocompatible, and histocompatible. The PLD adhesive may offer a promising and multifunctional alternative to conventional sutures for wound closure.

In this study, a cardanol-bonded chitin was synthesized for the first time via acylation of chitin dissolved in an ionic liquid, 1-allyl-3-methylimidazolium bromide, with an activated cardanol, prepared from 3-pentadecylphenoxy acetic acid and 1,1'-carbonyldiimidazole. Although the introduction of cardanol substituents induced no crystallization of the chitin chains and the appearance of a glass transition temperature (Tg), the resulting derivative did not exhibit useful properties, such as thermoplasticity for melt-press processing, due to strong interaction among the cardanol substituents. Therefore, the remaining hydroxy groups were further acylated using several fatty acyl chlorides in a LiCl/DMAc solvent to afford a series of cardanol-bonded mixed chitin esters entirely composed of naturally occurring moieties. The chemical structures and degrees of substitution (DSs) of the products were characterized by IR and 1H NMR spectroscopies. The obtained cardanol-bonded mixed chitin esters exhibited thermoplastic behavior owing to the reduced interaction among the cardanol substituents, accompanied by the appearance of Tgs, which enabled the film formation by melt-pressing at 150 °C at 15 MPa. The thermal properties of the derivatives, evaluated by differential scanning calorimetric analysis, were systematically discussed in accordance with structures and DSs of the substituents.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, with limited therapeutic options. Cucurbitacin B (CuB) demonstrates potent anti-HCC activity but suffers from systemic toxicity and poor pharmacokinetics. To address these challenges, we developed a series of asialoglycoprotein receptor (ASGPR)-targeted small molecule-drug conjugates (SMDCs) for the precision delivery of CuB. The trivalent conjugate SMDC 23 exhibited efficient ASGPR-mediated cellular uptake and controlled drug release. It induced both autophagy and immunogenic cell death, triggered ROS-mediated DNA damage, activated the DNA damage response, and arrested the cell cycle, consequently enhancing the radiosensitivity of HCC cells. In HepG2-derived models, SMDC 23 achieved superior tumor accumulation, suppressed tumor growth by 76% at 30 mg/kg, and synergized with low-dose radiotherapy (2 Gy) to achieve 98% tumor inhibition, all with no observable systemic toxicity. This ASGPR-targeted CuB platform, particularly in combination with radiotherapy, represents a promising precision chemoradiotherapy strategy for HCC.

Long-term tumor immunotherapy remains challenging due to poor drug retention and immune activation. Here, we proposed a chitosan-based composite hydrogel capable of in situ gelation at physiological temperature to form a durable depot for sustained and tumor microenvironment (TME)-responsive release. The system integrated indocyanine green (ICG)-loaded gold nanorods within boronic acid-modified mesoporous silica (GSB) and thermoresponsive nanocomposites (ICG@GAN), which were further loaded with β-glycerophosphate (β-GP) and genipin and embedded in a carboxymethyl chitosan matrix. Upon injection, sequential release of β-GP and genipin triggered rapid physical and stable chemical cross-linking, forming a high-strength double-network hydrogel. Gradual leaching of β-GP, along with enzymatic degradation of chitosan, sustained the release of ICG@GAN. In the TME, cleavage of boronate esters triggered the release of ICG and GSB, enabling synergistic photothermal and ROS-mediated tumor cell apoptosis and tumor-associated macrophage repolarization. Meanwhile, chitosan modulated the immune feedback to amplify immune activation and infiltration. This integrated hydrogel platform markedly suppressed tumor growth and metastasis, offering a promising strategy for long-term immunotherapy.

Efficient gene delivery coupled with tumor-specific cell death remains a key challenge in cancer gene therapy. Herein, we report a multifunctional cationic polymer (PFFc) that integrates gene delivery and ferroptosis induction. Low-molecular-weight PEI (600 Da) was used as a backbone and cross-linked with fluorinated and ferrocene-functionalized epoxides via ring-opening polymerization to yield fluorinated linker polymer (PF), ferrocene linker polymer (PFc), and their copolymer (PFFc). Fluorinated chains imparted hydrophobicity, self-assembly, and biocompatibility, while ROS-responsive thioacetal-ferrocene units served as an intracellular labile iron source, promoting Fenton reactions to induce ferroptosis. Structure-activity relationship studies showed that PFFc could achieve an optimal balance between the transfection efficiency and cytotoxicity. In proliferation assays, PFFc/p53 polyplexes exhibited strong gene-specific cytotoxicity, surpassing nontherapeutic controls (pGL-3) and even PF/p53 group, highlighting the critical role of p53. Mechanistically, PFFc/p53 simultaneously increased intracellular ROS via ferrocene-mediated Fenton reactions and suppressed the SLC7A11-GSH antioxidant axis, weakening antioxidant defenses and causing lipid peroxide accumulation, leading to efficient ferroptosis. Rescue experiments with ferroptosis inhibitors confirmed this mechanism. Overall, PFFc enables synergistic gene delivery and ferroptosis induction, achieving high transfection efficiency while precisely regulating programmed cell death, providing a promising platform for multifunctional antitumor nanomedicine.

N-Phenyloxycarbonyl-amino acids (NPCs) are promising monomers to synthesize both polypeptides and polypeptoids exhibiting great tolerance for nucleophiles. However, the polymerization mechanism of NPCs remains unclear since it is hard to distinguish intermediates including N-carboxyanhydrides (NCA) from byproducts of direct polycondensation. In this contribution, the polycondensation pathway is disproved by the impossible polymerization of alanine dimer NPC. Isocyanate acid (ICA) has been captured as an intermediate of NPC polymerization. In an attempt to monitor the polymerization of 15N-labeled leucine-NPC by 15N NMR for the first time, reactive species including ICA are identified and traced. A kinetic model is established based on the 15N NMR data and validated by Monte Carlo simulation. Two possible polymerization pathways are evidenced by a density functional theory (DFT) calculation. The ICA-meditated NCA ring-closing pathway is preferred over the direct NCA ring-closing pathway for lower Gibbs energy barriers. A direct ring-closing path is feasible only for Sar-NPC, which explains its low polymerization reactivity.

A diol symmetry-driven strategy was employed, tailoring the performance and end-of-life of bio-based aromatic copolyesters. A series of random copolyesters, BHB-PDn and BHB-HDn (n = 1-2.5), were synthesized via melt polycondensation of BHBB (diol) and BHMB (diester) with asymmetric 1,3-propanediol (PD) or symmetric 1,6-hexanediol (HD). Symmetric HD promoted semicrystalline domains (18-25%), yielding higher Tg (85.7-67.8 °C), tensile modulus (1.93-1.79 GPa), yield strength (65.7-47.5 MPa), and hydrophobicity (WCA 88.6-80.3°). In contrast, asymmetric PD produced predominantly amorphous domains (low crystallinity 8-15%) with enhanced ductility (εb 175-250%) and lower Tg (66.5-53.6 °C). Both series displayed excellent UV shielding (Tav-UVA < 4.7%, T400 nm <10%), significantly surpassing PET. Under enzymatic conditions with Thc_Cut1 cutinase (50 °C, 120 days), BHB-PD1.0 and BHB-HD1.0 achieved 35.5% and 30.8% weight loss, respectively, 4-fold higher than PET (<2%). This symmetry-controlled strategy offers a versatile pathway for next-generation sustainable polymers.

The interface of biomolecular condensates plays a crucial role in droplet stability, growth, and biochemical function, yet their properties remain poorly understood. Here, we develop an inhomogeneous mean-field theory to investigate the interfacial structure of condensates formed by polypeptides containing positively charged, polar, and aromatic residues in aqueous solutions. Our study focuses on the synergistic interplay between electrostatic interactions among charged residues and specific nonelectrostatic interactions among aromatics. We systematically explore how charge fraction α, aromatic fraction β, specific interaction strength εs, and salt concentration ρs regulate interfacial organization in aqueous solutions. At finite α, the condensate interface typically exhibits an electric double-layer structure with a positively charged periphery surrounded by a diffuse counterion cloud. In the absence of added salt, the polypeptide concentration profile develops a depletion layer on the supernatant side and an overshoot on the coacervate side of the interface. Increasing ρs narrows the interfacial width and weakens the local charge separation in condensates stabilized by specific attractions. The electrostatic potential displays an asymmetric diffuse profile across the interface. Overall, our predictions are qualitatively consistent with experimental observations, and the insights provided here may aid the rational design of biomolecular condensates with tailored interfacial properties.

Photodynamic therapy (PDT), a promising noninvasive antitumor therapeutic approach, can directly kill cancer cells and trigger an immunogenic cell death (ICD) effect by generating reactive oxygen species (ROS) and the cascade reactions of antitumor immunity. However, the hypoxic tumor microenvironment severely compromises the efficacy of PDT. To address this challenge, a self-oxycarrying nanoassembly POFF integrating the Type-I NIR photosensitizer tetrafluorophenyl bacteriochlorin (FBC) and an oxygen-carrying perfluorocarbon moiety was developed for amplified photoimmunotherapy via expanded ROS generation and hypoxia reversal. The nanoassembly exhibited "self-oxycarrying" capability and both enhanced Type-I and Type-II photodynamic performance to effectively alleviate hypoxia. Furthermore, in vitro and in vivo studies demonstrated that POFF possessed potent antitumor activity upon 750 nm laser light irradiation. The PDT-induced destruction of cancer cells released tumor-associated antigens, which, in turn, triggered a robust antitumor immune response and promoted the eradication of residual malignant cells. Collectively, this nanoassembly not only ameliorates the hypoxic tumor microenvironment but also provides a promising strategy to amplify the efficacy of photodynamic immunotherapy.

Supramolecular Polymers(SPs) can undergo reversible self-assemblyin response to internal or external stimuli. Design strategies basedon the benzene-1,3,5-tricarboxamide (BTA) core are gaining increasingattention. In this study, we describe a BTA amphiphile that self-assemblesinto supramolecular fibers in water and is able to respond to bothlight and enzymatic activity. An azobenzene moiety (AZB) and Gly-Phe-Leu-Glyamino acid sequence (GFLG) were incorporated into the BTA monomerskeleton to build three identical wedges that respond to light andCathepsin B activity. The synergistic application of two orthogonalstimuli enabled modulation of the assembly of BTA-AZB-GFLG fibersthrough the cooperative response to stimuli. These findings providenew insights into the use of SPs for future drug delivery applications.