Biomacromolecules
· 2026 Jun · PMID 42126553
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Collagen, the most abundant protein in animals, is a key structural component of muscle and connective tissues. Its structural integrity is strongly influenced by interactions with water; however, the molecular mechanism...Collagen, the most abundant protein in animals, is a key structural component of muscle and connective tissues. Its structural integrity is strongly influenced by interactions with water; however, the molecular mechanisms underlying these effects remain poorly understood. Here, we investigate dehydration-induced perturbations in collagen dynamics within the native bone extracellular matrix (ECM) using C solid-state Nuclear Magnetic Resonance (NMR) relaxation measurements (T and T) and associated rotational correlation times. This residue-specific approach reveals distinct dynamic behavior of the aliphatic carbons of the Gly-Pro-Hyp triplet and alanine, collectively constituting ∼70% of type I collagen. The C correlation times (10-10 s) demonstrate pronounced motional heterogeneity: dehydration predominantly restricts hydroxyproline C, whereas H/D-exchanged perturbs hydroxyproline C, C, and C, as well as glycine C. These findings establish C relaxation as a powerful tool for probing water-mediated collagen dynamics in native systems.
Bruckbauer A, Wnuk-Fink KMJ, Frisch T
… +2 more, Jaisingh A, Burkart MD
Biomacromolecules
· 2026 Jun · PMID 42121310
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Fully renewable materials will be a key component of sustainable plastic development and management, and the industrial reliance on petroleum-derived monomers, including aromatic diisocyanates used in polyurethanes (PUs)...Fully renewable materials will be a key component of sustainable plastic development and management, and the industrial reliance on petroleum-derived monomers, including aromatic diisocyanates used in polyurethanes (PUs), must be minimized to meet sustainability and production goals. To date, aliphatic diisocyanates have shown great promise as renewable monomers, and scalable production is imminent. This work demonstrates a systematic study and application of aliphatic diisocyanates for the preparation of rigid PU foams. Aliphatic 1,6-hexamethylene diisocyanate (6-HDI) was incorporated with multifunctional renewable polyols and cross-linkers to produce rigid polyurethane-polyisocyanurate foams with high renewable carbon content. Morphological, thermal, and mechanical analyses of these novel foams indicated similar properties and performance to those of commercial rigid foams. The described synthesis of rigid foams without utilization of aromatic diisocyanates broadens the scope of rigid foam formulations possible and serves to advance the understanding of renewable foam and material development.
Biomacromolecules
· 2026 Jun · PMID 42117528
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Atmospheric water harvesting (AWH) technology based on adsorption offers a promising solution to freshwater scarcity. Chitin nanocrystals/gelatin composite scaffolds were precisely constructed via direct ink writing (DIW...Atmospheric water harvesting (AWH) technology based on adsorption offers a promising solution to freshwater scarcity. Chitin nanocrystals/gelatin composite scaffolds were precisely constructed via direct ink writing (DIW) 3D printing in this study. After polydopamine coating was applied to endow the scaffold with photothermal conversion properties, the scaffold was further impregnated with lithium chloride to introduce hygroscopicity. This process produced a hierarchical porous material for AWH. Compared to traditional aerogels, this 3D-printed scaffold exhibited approximately 59.5% higher water uptake and nearly 1.99 times higher average water sorption rate within 30 min. The scaffold demonstrated stable hygroscopic performance across a broad humidity range (30-90% RH). Under natural outdoor sunlight, the material achieved an average daily water yield of approximately 0.60 g g. This study introduces a structurally controllable, performance-stable hygroscopic salt-based biomacromolecule composite for AWH, demonstrating potential for agricultural applications and environmental sustainability.
Mu W, Chen Y, Zhong Z
… +6 more, De Baere J, Lauwers H, Defreyne D, Peng H, De Geest BG, Louage B
Biomacromolecules
· 2026 Jun · PMID 42114014
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Fibroblast activation protein (FAP) is selectively overexpressed on cancer-associated fibroblasts (CAFs), making it a prime target for reshaping the tumor microenvironment. Antibody-recruiting molecules (ARMs) offer a mo...Fibroblast activation protein (FAP) is selectively overexpressed on cancer-associated fibroblasts (CAFs), making it a prime target for reshaping the tumor microenvironment. Antibody-recruiting molecules (ARMs) offer a monoclonal antibody alternative by enabling endogenous antibodies binding to eliminate target cells. Here, we report the development of multivalent FAP-targeting ARMs based on a truncated derivative of the high-affinity small-molecule OncoFAP. Initial attempts to generate monovalent ARMs by conjugating the FAPL to dinitrophenol (DNP) failed to enable antibody recruitment, despite efficient ligand binding. To overcome steric limitations, FAPL and DNP were coconjugated onto a 150 kDa dextran scaffold for multivalent display of FAP and antibody binding motifs. These dextran-based ARMs efficiently recruited anti-DNP antibodies, triggered robust complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP) of FAP-expressing cells in vitro. Our findings demonstrate that multivalent macromolecular scaffolds effectively enable small-molecule-mediated antibody recruitment to noninternalizing targets like FAP, highlighting their potential for therapeutic tumor stroma remodeling.
Wang Y, Yu H, Zhang R
… +4 more, Chen X, Zhang B, Sun D, Guo Y
Biomacromolecules
· 2026 Jun · PMID 42112663
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To address surgical site infections (SSIs), we developed a core-sheath suture via electrospinning consisting of a robust silk core for mechanical strength and a functionalized polycaprolactone (PCL) nanofiber sheath. The...To address surgical site infections (SSIs), we developed a core-sheath suture via electrospinning consisting of a robust silk core for mechanical strength and a functionalized polycaprolactone (PCL) nanofiber sheath. The antimicrobial peptide KR-12 was covalently immobilized onto the sheath, enabling potent antibacterial activity while mitigating cytotoxicity. The suture exhibited broad-spectrum efficacy against Gram-positive and Gram-negative bacteria, including MRSA, and significantly inhibited biofilm formation. It provided sustained antibacterial performance for up to 14 days, with over 97% inhibition against and . Additionally, this demonstrated favorable cytocompatibility. In infected skin wounds, the suture promoted healing by reducing inflammatory infiltration, stimulating collagen regeneration, and downregulating TNF-α expression. This mechanically strong, biocompatible, and persistently antibacterial suture offers a promising strategy for the prevention of SSIs.
Lyu CY, Guo Y, Weng C
… +5 more, Lu M, Wan S, Liu K, Tang X, Lu H
Biomacromolecules
· 2026 Jun · PMID 42099288
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Structural regularity in polymers is a double-edged sword, enhancing crystallinity and thermal stability but often reducing processability and toughness. Here, we present a substitution-desymmetrization strategy to addre...Structural regularity in polymers is a double-edged sword, enhancing crystallinity and thermal stability but often reducing processability and toughness. Here, we present a substitution-desymmetrization strategy to address this trade-off in chemically recyclable polythioesters (PTEs). Copolymerizing symmetric β-gem-dimethyl thiolactone with an asymmetric β-methyl-β-ethyl analog via rare-earth metal-catalyzed ring-opening polymerization enables precise backbone symmetry control, yielding tunable melting temperatures (90-170 °C) and ductility. The optimized copolymer self-assembles into hierarchical helical nanofiber bundles, achieving strong adhesion across substrates (lap-shear strength up to 9.48 MPa on iron). The adhesive performs well at extreme temperatures (-196 and 120 °C) and shows superior water resistance compared to commercial cyanoacrylate. Moreover, PTEs remain fully chemically recyclable. This work offers a sustainable platform for high-performance materials via symmetry engineering.
Biomacromolecules
· 2026 Jun · PMID 42099228
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Biomimetic hydrogels with great mechanical properties that provide stable and low-impedance interfaces are essential for long-term wearable bioelectronics. In this study, we developed dopamine-grafted carboxymethyl cellu...Biomimetic hydrogels with great mechanical properties that provide stable and low-impedance interfaces are essential for long-term wearable bioelectronics. In this study, we developed dopamine-grafted carboxymethyl cellulose (CMCDA) hydrogel and oxidative cross-linking form (CMCDA'). Using multidimensional (1D/2D) NMR techniques, we provide detailed structural elucidation of dopamine-grafted polysaccharides, offering new insights into amide formation, Schiff base/Michael addition structures, and partially oxidized polydopamine segments. The cross-linked CMCDA' hydrogels are mechanically robust, highly hydrophilic, and strongly adhesive on various substrates, enabling conformal skin contact. After electrolyte exchange with saturated NaCl, CMCDA' becomes ionically conductive (5-10 S m) and maintains stable impedance under continuous hydration. Integrated as a wearable electrode interface, CMCDA' supports reliable electrocardiogram acquisition for one week, outperforming the commercial conductive gel at curved body sites. These results highlight oxidative-cross-linked, cellulose-derived hydrogels as sustainable ionically conductive interfaces for long-term wearable bioelectronics.
Ma Y, Wang N, Li R
… +6 more, Yan X, Shangguan J, Huang C, Yuan X, Jia J, Liu A
Biomacromolecules
· 2026 Jun · PMID 42098941
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α-Lipoic acid (LA), a natural cyclic disulfide, has emerged as a versatile building block for next-generation adhesives because of its ring-opening polymerization and dynamic disulfide exchange. This review summarizes re...α-Lipoic acid (LA), a natural cyclic disulfide, has emerged as a versatile building block for next-generation adhesives because of its ring-opening polymerization and dynamic disulfide exchange. This review summarizes recent advances in LA-based adhesives, focusing on strategies for stabilizing poly(LA) networks through radical quenching, supramolecular assembly, metal-ligand coordination, and deep eutectic architectures. We discuss the interfacial mechanisms underlying robust wet and underwater adhesion, where dense carboxyl groups enable multivalent hydrogen-bonding and ionic interactions. LA-based adhesives also integrate self-healing, recyclability, and intrinsic bioactivity, including antioxidant and antimicrobial functions. These features support applications in hemostasis, wound repair, wearable iontronics, and sustainable industrial bonding. Finally, key challenges, including the trade-off between network stability and dynamicity and the need for scalable manufacturing, are highlighted to guide the future development of circular, smart, and bioactive adhesive materials.
Bastami B, Rashidi Ranjbar P, Adeli M
… +1 more, Beyranvand S
Biomacromolecules
· 2026 May · PMID 42095698
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The development of multifunctional polymer therapeutics aligned with circular chemistry principles requires renewable building blocks, efficient synthesis, and enhanced material longevity. Herein, we report a circular-by...The development of multifunctional polymer therapeutics aligned with circular chemistry principles requires renewable building blocks, efficient synthesis, and enhanced material longevity. Herein, we report a circular-by-design zwitterionic pseudodendrimer based on hyperbranched polyglycerol-polyoxazoline-lysine (hPG--POX-Lys) that integrates antimicrobial activity with targeted anticancer drug delivery. Hyperbranched polyglycerol, derived from glycidol feedstocks, was selectively mesylated and used as a macroinitiator for ring-opening polymerization of 2-ethyl-2-oxazoline, followed by lysine functionalization. The modular synthesis afforded the polymer in 76% yield with high functional density and minimal steps. The zwitterionic architecture exhibited intrinsic antibacterial activity against and with low cytotoxicity. The nanostructure achieved high loading capacity (81.25%) for the CDK4/6 inhibitor palbociclib and enabled efficient in vitro delivery, improving selectivity toward cancer cells. This platform demonstrates a scalable strategy for multifunctional, circular nanomedicine design.
Schäfer G, Tang Q, Zhang H
… +5 more, Thisgaard H, Baun C, Straathof NJW, Barz M, Jensen AI
Biomacromolecules
· 2026 Jun · PMID 42095635
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Glioblastoma continues to be one of the most lethal and treatment-refractory forms of brain cancer. In this study, we report the development of a novel nanocarrier ("PeptoBrush") for the sustained release of the Auger-em...Glioblastoma continues to be one of the most lethal and treatment-refractory forms of brain cancer. In this study, we report the development of a novel nanocarrier ("PeptoBrush") for the sustained release of the Auger-emitting radiotherapeutic agent [I]iododeoxyuridine ([I]IUdR). The PeptoBrush scaffold, consisting of a polyglutamic acid backbone with degree of polymerization (DP) of 100 grafted with polysarcosine with DP of 82 (30% grafting density with respect to pGlu) and DBCO units (16% grafting density with respect to pGlu), was synthesized, and [I]IUdR was conjugated via strain-promoted azide-alkyne cycloaddition (SPAAC). The resulting radioconjugate exhibited a defined spherical morphology with a hydrodynamic diameter of 12.1 ± 1.9 nm and ξ-potential of -4.0 ± 1.4 mV. In vitro release studies demonstrated esterase-responsive release of [I]IUdR, supporting a sustained release profile. DNA incorporation assays and viability studies in glioblastoma cells confirmed the biological activity and radiotoxicity of the released compound. This work highlights the potential of PeptoBrushes for controlled radionuclide delivery of Auger-emitting radiotherapeutic agents, laying the foundation for an innovative strategy in glioblastoma therapy.
Biomacromolecules
· 2026 Jun · PMID 42091048
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Pulmonary bacterial infections pose a serious threat to public health and are a challenging problem for conventional antibiotic treatment. Phototherapy is a potential solution, but the collateral damage to normal tissues...Pulmonary bacterial infections pose a serious threat to public health and are a challenging problem for conventional antibiotic treatment. Phototherapy is a potential solution, but the collateral damage to normal tissues often limits the therapeutic efficacy because of the lack of bacteria-targeting ability. In this study, a ()-targeted polymeric nanotherapeutic agent (pLAMA--pPc) containing phthalocyanine and a galactose fragment was synthesized via reversible addition-fragmentation chain-transfer polymerization. The galactose monomer incorporated into the copolymer increased the water solubility and specificity of phthalocyanine photosensitizers. pLAMA--pPc can specifically adhere to the surface via Lec A in the extracellular polymeric substances and can effectively kill by near-infrared-light-induced singlet oxygen and hyperthermia without affecting normal mammalian cells. An study of the -induced pulmonary infection model shows that pLAMA--pPc has been concentrated at the infection site after injection of the tail vein for 5 h, which was verified by fluorescence imaging. Near-infrared light irradiation on mouse lungs could achieve accurate treatment of pulmonary bacterial infections. This work provides a targeted antibacterial treatment for nonantibiotics and accurate treatment of focal infection.
Biomacromolecules
· 2026 Jun · PMID 42090587
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Electrospun elastic scaffolds are promising for small-diameter vascular grafts, but balancing electrospinnability with native-like mechanical properties remains challenging. To address this, various ABA (PCL--PMCL--PCL)...Electrospun elastic scaffolds are promising for small-diameter vascular grafts, but balancing electrospinnability with native-like mechanical properties remains challenging. To address this, various ABA (PCL--PMCL--PCL) and BAB (PMCL--PCL--PMCL) elastomers were synthesized. It was revealed that rapid crystallization promoted uniform, bead-free fibers, and ABA-type copolymers exhibited better elastic recovery than BAB types. To optimize both the electrospinnability and mechanics, the ABA3 copolymer was selected to fabricate grafts. It was demonstrated that the grafts had a tensile strength of 3.99 ± 0.15 MPa and a high compliance of 9.62 ± 0.85%/100 mmHg, perfectly matching those of native blood vessels. Additionally, the grafts showed excellent cytocompatibility, supporting cell growth over 5 days. Ultimately, these elastomers synergize excellent electrospinnability with biomimetic mechanics, offering a highly effective strategy for developing small-diameter vascular prostheses.
Wang X, Han RB, Ding X
… +4 more, Xiao L, Luo YW, Huang XH, Hu YJ
Biomacromolecules
· 2026 Jun · PMID 42089837
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Drug-resistant bacterial biofilm infections severely impede wound healing. Here, we report a nanozyme-integrated hydrogel (HEA@OAH) that combines high-entropy alloy nanozymes with an injectable self-healing hydrogel cros...Drug-resistant bacterial biofilm infections severely impede wound healing. Here, we report a nanozyme-integrated hydrogel (HEA@OAH) that combines high-entropy alloy nanozymes with an injectable self-healing hydrogel cross-linked by dynamic Schiff base bonds for treating methicillin-resistant () biofilm-infected wounds. Under NIR irradiation, HEA@OAH exerts photothermal therapy to disrupt biofilms and photothermally enhances dual enzyme-mimicking activities: peroxidase-like activity generates bactericidal ·OH from HO, while glutathione peroxidase-like activity scavenges excess HO, to protect tissue. Theoretical calculations reveal the synergistic effects of multimetallic sites. In vitro, the reduction rate of the biofilm reached 84.5%. , it effectively eliminates biofilms, alleviates inflammation, and promotes near-scarless wound healing. This study provides a synergistic therapeutic strategy for next-generation intelligent wound dressings.
Biomacromolecules
· 2026 Jun · PMID 42086458
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Lanthanides are attractive ionic cross-linkers for connecting hydrophilic polymers to form luminescent hydrogels. However, lanthanide-complexed networks often lack mechanical robustness. Here, precoordinated lanthanide c...Lanthanides are attractive ionic cross-linkers for connecting hydrophilic polymers to form luminescent hydrogels. However, lanthanide-complexed networks often lack mechanical robustness. Here, precoordinated lanthanide complexes are introduced as both luminophores and dynamic cross-linkers to fabricate mechanically stable alginate hydrogels. Three types of precoordinated lanthanide complexes featuring lanthanides of varying ionic sizes (i.e., terbium (Tb), europium (Eu), and samarium (Sm)) spontaneously cross-link alginate through electrostatic interactions to form Alg-Ln hydrogels. The Alg-Sm hydrogel exhibits a shorter gelation time, a denser network, and superior mechanical strength compared to Alg-Eu and Alg-Tb hydrogels. These results are attributed to the larger volume of the Sm complex, which increases the spacing between polymer chains and promotes the formation of more electrostatic cross-linking points. Additionally, the Alg-Eu hydrogel serves as a promising luminescent sensor for copper ions. Taken together, the use of precoordinated lanthanide complexes as cross-linking agents enables tailored customization of hydrogel structures and properties.
Yen YS, Su KH, Zhang CW
… +8 more, Huang YC, Yu SC, Yu DY, Jeng US, Su CJ, Chuang WT, Shih O, Hsu HY
Biomacromolecules
· 2026 Jun · PMID 42085556
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Supramolecular hydrogels coassembled from drugs and natural low-molecular-weight gelators (LMWGs) offer favorable physicochemical properties, tunable mechanics, and controlled drug release; however, elucidating their in...Supramolecular hydrogels coassembled from drugs and natural low-molecular-weight gelators (LMWGs) offer favorable physicochemical properties, tunable mechanics, and controlled drug release; however, elucidating their in situ fibrillar architecture remains a major challenge. Here, we report a fully natural G-quadruplex hydrogel formed by coassembling 5'-guanosine monophosphate (GMP) with phytic acid (PA), which serves as both a natural cross-linker and a bioactive therapeutic molecule. Systematic modulation of the GMP/PA ratio revealed a delicate compositional balance governing gel formation, mechanical strength, and pH-dependent molecular interactions. Small- and wide-angle X-ray scattering (SWAXS) combined with CRYSOL-assisted atomistic modeling resolved the hierarchical organization of GMP fibrils and demonstrated that PA promotes surface clustering and interfibril bundling through multivalent electrostatic interactions. Molecular dynamics simulations further confirmed PA-mediated stabilization of the G-quadruplex assemblies under hydrated conditions. Kinetic analysis revealed that densification of fibrillar networks effectively slowed scaffold degradation and enabled sustained PA release, transitioning from zero- to first-order kinetics with increasing structural order. Collectively, this study establishes a direct correlation between molecular architecture, mechanical strength, and release dynamics, presenting a structural framework for the rational design of bioactive, G-quadruplex-based hydrogels for advanced drug delivery applications.
Tortorella A, Petraccone L, Del Vecchio P
… +2 more, Oliva R, Winter R
Biomacromolecules
· 2026 Jun · PMID 42085529
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The first contact of polyphenols with the human body occurs in the mouth, where they are known to interact with proline-rich proteins (PRPs), leading to physicochemical and biochemical changes in the salivary pellicles a...The first contact of polyphenols with the human body occurs in the mouth, where they are known to interact with proline-rich proteins (PRPs), leading to physicochemical and biochemical changes in the salivary pellicles and epithelia of the oral cavity. These interactions are important at the sensory level for the development of astringency. Organoleptic tests have also shown that astringency can be attenuated when fatty foods are consumed, a phenomenon known as the Camembert effect. Employing isothermal titration calorimetry, fluorescence, and CD spectroscopy, we investigated the binding process of the prototypical polyphenol catechin to the PRP IB9-37, also in the presence of 10 vol % ethanol, which is known to influence polyphenol interactions, and in the presence of fatty acids. Our results show that the binding of catechin to IB9-37 is characterized by weak binding, and the binding strength increases markedly in hydroalcoholic solution. The calorimetric data show that the binding process is largely enthalpy-driven, but solvent-related hydrophobic interactions are present as well in the absence of ethanol. We found that significantly higher binding affinities are observed when catechin binds to stearic and oleic acids, indicating that the interaction of the polyphenol with lipid molecules in fatty food boluses is expected to be at least an order of magnitude stronger than with salivary proteins. This clearly shows that fats can prevent the formation of irritating polyphenol-protein interactions, which is consistent with the common understanding of the Camembert effect. Remarkably, binding of the fatty acids to the PRP is also an order of magnitude stronger compared to the catechin-polypeptide interaction; therefore, it will also contribute significantly to reducing astringency. Overall, using a prototypical model system, we were able to obtain a detailed molecular picture of the binary interactions that contribute to these effects and uncover the underlying driving forces that help us to understand them.
Zhou Q, Lai M, Huang J
… +6 more, Zhang T, Zhou Z, Zong W, Feng Q, Hu C, Jiang M
Biomacromolecules
· 2026 Jun · PMID 42084958
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Natural polymer-based nanocarrier-controlled drug delivery systems are of great significance for achieving efficient and cost-effective therapeutics. Herein, we report the fabrication of berberine hydrochloride (BBR) loa...Natural polymer-based nanocarrier-controlled drug delivery systems are of great significance for achieving efficient and cost-effective therapeutics. Herein, we report the fabrication of berberine hydrochloride (BBR) loaded lignin nanotubes (LNTs) via a coassembly process. The resulting nanocarriers with BBR homogeneously dispersed in the LNT matrix, with a maximum 16.48% drug loading, exhibit 168 h of sustained release dominated by the Fickian diffusion mechanism. Moreover, the drug delivery system holds photothermal activity (a temperature elevation from 29 to 45 °C within 10 min under 0.2 W cm irradiation), antibacterial efficacy against (95.3%), and antioxidant capacity (with a DPPH radical scavenging rate of 91.22%). The coassembled nanocarrier system is successfully achieved under cryogenic conditions mainly driven by π-π interactions between aromatic nuclei and hydrogen-bonding interactions of side chains within the lignin structure. The molecular interactions between BBR and lignin were elucidated to be electrostatic interactions and hydrogen bonding.
Wang M, Yu J, Zhang L
… +10 more, Li W, Han W, Guo J, Luo M, Liu H, Liu H, Xu H, Chen J, Du L, Zhang Y
Biomacromolecules
· 2026 Jun · PMID 42068279
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Nanoprodrug, utilizing precisely engineered nanomaterial as both a carrier and a caging agent, enables targeted delivery and precise release of toxic antitumor drugs into tumor tissues. To further promote the stability a...Nanoprodrug, utilizing precisely engineered nanomaterial as both a carrier and a caging agent, enables targeted delivery and precise release of toxic antitumor drugs into tumor tissues. To further promote the stability and tumor selectivity, a series of hyperbranched polymer-based unimolecular nanoprodrugs were prepared and analyzed. The toxic drug camptothecin was covalently conjugated to the nanostructures through glutathione cleavable linkers to allow for potent release in tumors. A γ-glutamyl transferase responsive moiety was decorated on the nanoprodrugs to tune the surface charges and promote cancer cell uptake. By combining the advantages of stimuli-responsiveness and the stable polymeric nanostructure, the optimized nanoprodrug showed satisfactory cancer/normal cell selectivity, safety, and anticancer efficacy both in vitro and in vivo.
Acharya B, Lamichhane S, Brown TP
… +2 more, Chavent M, Im W
Biomacromolecules
· 2026 Jun · PMID 42065970
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The mycobacterial outer membrane (MOM) constitutes an asymmetric permeability barrier that influences lipid organization and transport in . In this study, we have developed Martini 3 coarse-grained (CG) lipid models of t...The mycobacterial outer membrane (MOM) constitutes an asymmetric permeability barrier that influences lipid organization and transport in . In this study, we have developed Martini 3 coarse-grained (CG) lipid models of the MOM, incorporating α-mycolic acids, 5 different trehalose-based lipids, and PDIM (phthiocerol dimycocerosate). The CG models were parametrized and validated using all-atom simulations of symmetric inner- and outer-leaflet membranes, as well as fully asymmetric MOM models. Bonded parameters were optimized through an iterative refinement procedure targeting atomistic bonded distributions. The CG simulations show good agreement with the all-atom simulation data and available experimental measurements in terms of membrane thickness, solvent accessible surface area, lipid density profiles, and outer-leaflet-induced lipid disorder in α-mycolic acids at the inner leaflet. The model also reproduces the temperature-dependent phase behavior of all-atom α-mycolic acid membranes. Using this model, we demonstrate that PDIM localization, diffusion, and aggregation are strongly modulated by membrane fluidity and lipid composition with enhanced translocation and clustering in liquid disordered environments. Our CG MOM lipid models provide a validated platform for large-scale simulations of mycobacterial membranes and enable mechanistic studies of lipid organization, membrane dynamics, and protein-membrane and membrane-drug interactions.
Li W, Liu M, Liu S
… +4 more, Tao Z, Ma H, Zhang W, Tian J
Biomacromolecules
· 2026 Jun · PMID 42065366
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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 ca...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.