{"title":"Impact of Composition of Lipid-Based Formulations on First-Pass Drug Metabolism after Oral Administration.","authors":"Yusuke Tanaka, Rikuto Fukaishi, Daiki Okamoto, Takanori Kurakazu, Tokio Nakai, Haruya Yagi, Shinji Sakuma","doi":"10.1021/acs.molpharmaceut.4c01299","DOIUrl":"10.1021/acs.molpharmaceut.4c01299","url":null,"abstract":"<p><p>This study aimed to elucidate the drug absorption mechanisms after oral administration of lipid-based formulations (LBFs), emphasizing the impact of their composition on first-pass drug metabolism. Ketoconazole (KTZ), a CYP3A substrate, was loaded into two types of LBFs: a long-chain LBF (type II-LC) and a lipid-free formulation (type IV). Following oral administration of type II-LC, the systemic exposure of KTZ was lower compared to that for the type IV and a control suspension. However, pretreatment with 1-aminobenzotriazole, a nonspecific CYP inhibitor, revealed equivalent in vivo exposure among the formulations tested. The absorption of KTZ from type II-LC in the early period was slower than that from the suspension and type IV. Experiments on in vitro digestion in sequence with in vitro permeation across a dialysis membrane showed that the drug permeation rate for type II-LC was extremely low. This was probably due to the reduction in free drug molecules in the donor compartment via the incorporation of KTZ into mixed micelles comprising digestion products derived from type II-LC and bile components. Furthermore, luminal concentration measurements revealed that gastric emptying was delayed when a type II-LC was administered. The reduced free drug concentration and transient delay in gastric emptying of KTZ resulted in the slower absorption of KTZ for type II-LC. The product of the fraction of drug absorbed and fraction of the drug not metabolized in the gut wall (Fa × Fg) calculated from the systemic and portal plasma concentration-time courses of KTZ was 0.185 for type II-LC and 0.327 for suspension. Since the luminal concentration measurement demonstrated complete absorption of KTZ from the gastrointestinal tract (Fa ≅ 1), the Fa × Fg values can be regarded as Fg. In conclusion, the lower in vivo exposure following oral administration of type II-LC was attributed to reduced Fg, that is, slower drug absorption from the jejunum resulted in low KTZ concentration in enterocytes, leading to enhanced metabolic efficiency. Our findings can be valuable when selecting excipients for designing LBFs with the preferred in vivo performance for highly metabolized drugs.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2098-2107"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular PharmaceuticsPub Date : 2025-04-07Epub Date: 2025-03-27DOI: 10.1021/acs.molpharmaceut.5c00072
Dan Wen, Qi Wang, Jin Ding, Zilei Wang, Shiyu Lin, Hao Zhang, Xiaohong Huang, Xiaokun Ma, Xingguo Hou, Suping Li, Hua Zhu, Zhi Yang
{"title":"Construction of Bispecific T-Cell Engager Radiotracer and Its Micro-PET Evaluation in Pancreatic Cancer.","authors":"Dan Wen, Qi Wang, Jin Ding, Zilei Wang, Shiyu Lin, Hao Zhang, Xiaohong Huang, Xiaokun Ma, Xingguo Hou, Suping Li, Hua Zhu, Zhi Yang","doi":"10.1021/acs.molpharmaceut.5c00072","DOIUrl":"10.1021/acs.molpharmaceut.5c00072","url":null,"abstract":"<p><p>Mucin 17 (MUC17), a transmembrane mucin, is overexpressed in pancreatic cancer and is associated with tumor proliferation and metastasis. CD3 is an indispensable molecule on the surface of T lymphocytes, which is associated with T cell activation and participates in immune responses. Here, we developed a bispecific T-cell engager radiotracer, <sup>89</sup>Zr-M17C3, targeting MUC17 and CD3, to enable noninvasive PET imaging of both tumor cells and T-cell infiltration in pancreatic cancer. <sup>89</sup>Zr-M17C3 was synthesized by conjugating AMG199 with zirconium-89 and verified for its radiochemical purity and in vitro stability. The <sup>89</sup>Zr-M17C3 probe demonstrated excellent radiochemical purity (>99%) and stability (maintained ≥99% over 120 h). Cellular uptake assays and binding affinity studies were conducted to evaluate the probe's specificity for MUC17 and CD3. Micro-PET/CT imaging and biodistribution studies were performed in MUC17-expressing nude mice and CD3 humanized mice to assess probe uptake in tumors and T-cell-infiltrated tissues. In MUC17-expressing AsPC-1 tumors, probe uptake was significantly higher than in MUC17-negative PANC-1 tumors (SUVmax: 2.26 ± 0.18 vs 1.13 ± 0.14, <i>P</i> < 0.001) and was confirmed to be MUC17-dependent through blocking studies. In CD3 humanized mice, the probe was able to visualize both T-cell infiltration and MUC17-positive tumors, with peak uptake in AsPC-1 tumors (SUVmax: 2.35 ± 0.46) and spleen (SUVmax: 2.19 ± 0.40) at 216 h. Immunohistochemical analysis confirmed the spatial correlation between MUC17 expression and CD3-positive T-cell infiltration in AsPC-1 tumors but not in PANC-1 tumors. In summary, the <sup>89</sup>Zr-M17C3 radiotracer exhibited high affinity for MUC17 and CD3 and successfully differentiated MUC17-positive tumors from MUC17-negative tumors while simultaneously providing insight into the T-cell distribution. This study highlights the potential of <sup>89</sup>Zr-M17C3 as a versatile imaging tool to support patient stratification and therapeutic monitoring in tumor-targeted immunotherapy, particularly for bispecific T-cell engager-based approaches such as AMG199.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2276-2286"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lukas Hasecke, Maximilian Breitenbach, Martí Gimferrer, Rainer Oswald, Ricardo A Mata
{"title":"Addressing Anharmonic Effects with Density-Fitted Multicomponent Density Functional Theory.","authors":"Lukas Hasecke, Maximilian Breitenbach, Martí Gimferrer, Rainer Oswald, Ricardo A Mata","doi":"10.1021/acs.jpca.5c00382","DOIUrl":"https://doi.org/10.1021/acs.jpca.5c00382","url":null,"abstract":"<p><p>In this contribution we present the first local density-fitted multicomponent density functional theory implementation and assess its use for the calculation of anharmonic zero-point energies. Four challenging cases of molecular aggregates are reviewed: deprotonated formic acid trimer, diphenyl ether-<i>tert</i>-butyl alcohol conformers, anisole/methanol and anisole/2-naphtol dimers. These are all cases where a mismatch between the low-temperature computationally predicted minimum and the experimentally determined structure was observed. Through the use of nuclear-electronic orbital energies in the thermodynamic correction, the correct energetic ordering is recovered. For the smallest system, we compare our results to vibrational perturbation theory anharmonically corrected zero-point energy, with perfect agreement for the lower-lying conformers. The performance of the newly developed code and the density fitting errors are also analyzed. Overall, the new implementation shows a very good scaling with system size and the density fitting approximations exhibit a negligible impact.</p>","PeriodicalId":59,"journal":{"name":"The Journal of Physical Chemistry A","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular Studies and Advanced Visualization of the Trapping of Methane Nanobubbles during Hydrate Growth.","authors":"Temitayo Adeyemi, Olufemi Olorode","doi":"10.1021/acs.jpcb.4c07851","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c07851","url":null,"abstract":"<p><p>The potential application of gas hydrates in storing clean energy has increased the interest in studying clathrate hydrates of gases like methane, CO<sub>2</sub>, and hydrogen. In this work, we conduct large-scale molecular studies of methane hydrate growth and visualize the simulation results using mixed reality (MR) headsets and regular two-dimensional snapshots of the simulation domain. The results show the novel molecular observation of the trapping of gas nanobubbles within the growing solid hydrate. Our first-of-a-kind visualization of the internal hydrate structures in mixed reality enabled the length measurements of the simulation domain and nanobubble sizes, which showed that the gas nanobubbles were up to 9 nm in diameter. This is bigger than the simulation domain commonly used in atomistic gas hydrate studies, which explains why this is the first observation of the trapping of methane gas nanobubbles within a growing hydrate. Furthermore, our estimates of the increased storage due to the trapping of the nanobubbles indicate a 37% increase in the weight percentage of methane stored. Although this work focused on nanobubble-enhanced methane storage in hydrates, the idea, methods, and tools developed can be leveraged to enhance the storage of other gases, like hydrogen and CO<sub>2</sub>. This study also revealed that the presence of gas nanobubbles accelerates the rate of hydrate formation, which is consistent with experimental observations. Finally, we expect our workflow for MR visualization of gas hydrate structures to facilitate other novel observations and insights from molecular dynamics (MD) studies of gas hydrates.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ACS Materials LettersPub Date : 2025-04-07DOI: 10.1021/acsmaterialslett.5c0050510.1021/acsmaterialslett.5c00505
Natalie Banerji*,
{"title":"How to Make Electronics Flexible─Recent Advances in Materials, Processing, and Applications","authors":"Natalie Banerji*, ","doi":"10.1021/acsmaterialslett.5c0050510.1021/acsmaterialslett.5c00505","DOIUrl":"https://doi.org/10.1021/acsmaterialslett.5c00505https://doi.org/10.1021/acsmaterialslett.5c00505","url":null,"abstract":"","PeriodicalId":19,"journal":{"name":"ACS Materials Letters","volume":"7 4","pages":"1419–1420 1419–1420"},"PeriodicalIF":9.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular PharmaceuticsPub Date : 2025-04-07Epub Date: 2025-03-12DOI: 10.1021/acs.molpharmaceut.4c01445
Donglan Huang, Yiming Guo, Mengchao Cui, Hualong Fu
{"title":"Development and Preliminary Evaluation of a <sup>125</sup>I-Labeled Radioligand ([<sup>125</sup>I]iodotrazoline) for In Vitro Detection of Imidazoline-2 Binding Site in the Brain.","authors":"Donglan Huang, Yiming Guo, Mengchao Cui, Hualong Fu","doi":"10.1021/acs.molpharmaceut.4c01445","DOIUrl":"10.1021/acs.molpharmaceut.4c01445","url":null,"abstract":"<p><p>Astrocytes exert multiple functions within the brain, including regulating neuroinflammation and maintaining homeostasis, and the reactive astrocytes are implicated in many neurodegenerative disorders. Imidazoline-2 binding site (I<sub>2</sub>BS) has been established as a reliable biomarker for precisely quantifying reactive astrocytes. Here, we reported the development of [<sup>125</sup>I]iodotrazoline ([<sup>125</sup>I]<b>8</b>), a novel I<sub>2</sub>BS radioligand with high affinity (<i>K</i><sub>i</sub> = 6.8 nM) and exceptional selectivity over α<sub>2</sub>-adrenoceptors (>1400 folds). <i>In vitro</i> autoradiography (ARG) using rat brain sections revealed a heterogeneous distribution of [<sup>125</sup>I]<b>8</b>, with high signals in the medulla, midbrain, pons, and hypothalamus. Pretreatment with unlabeled I<sub>2</sub>BS-selective ligands, BU224 and FTIMD, reduced the binding by >30%, indicating high <i>in vitro</i> specificity for I<sub>2</sub>BS. <i>Ex vivo</i> ARG results confirmed this distribution pattern in the rat brain. Biodistribution results in mice demonstrated a rapid brain uptake of [<sup>125</sup>I]<b>8</b> (3.35% ID/g at 2 min postinjection) with slow washout. Metabolite analysis exhibited the desirable biostability of [<sup>125</sup>I]<b>8</b> in the rat brain. Altogether, this work provides a new <sup>125</sup>I-labeled radioligand featuring a novel 2-trans-styryl-imidazoline scaffold, which shows significant specificity binding for I<sub>2</sub>BS <i>in vitro</i>, serving as a valuable tool for I<sub>2</sub>BS detection and astrocyte-related pathology research.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2224-2232"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular PharmaceuticsPub Date : 2025-04-07Epub Date: 2025-03-13DOI: 10.1021/acs.molpharmaceut.4c01534
Ben Forbes, Per Bäckman, Antonio Cabal, Andy Clark, Carsten Ehrhardt, Jayne E Hastedt, Anthony J Hickey, Guenther Hochhaus, Wenlei Jiang, Stavros Kassinos, Philip J Kuehl, Bo Olsson, David Prime, Yoen-Ju Son, Simon Teague, Ulrika Tehler, Jennifer Wylie
{"title":"iBCS: 4. Application of the Inhalation Biopharmaceutics Classification System to the Development of Orally Inhaled Drug Products.","authors":"Ben Forbes, Per Bäckman, Antonio Cabal, Andy Clark, Carsten Ehrhardt, Jayne E Hastedt, Anthony J Hickey, Guenther Hochhaus, Wenlei Jiang, Stavros Kassinos, Philip J Kuehl, Bo Olsson, David Prime, Yoen-Ju Son, Simon Teague, Ulrika Tehler, Jennifer Wylie","doi":"10.1021/acs.molpharmaceut.4c01534","DOIUrl":"10.1021/acs.molpharmaceut.4c01534","url":null,"abstract":"<p><p>This is the fourth paper in a series describing an inhalation biopharmaceutics classification system (iBCS), an initiative supported by the Product Quality Research Institute. The paper examines the application of the inhalation Biopharmaceutics Classification System (iBCS) through the drug discovery, development, and postapproval phases for orally inhaled drug products (OIDP) and for the development of generic OIDPs. We consider the implication of the iBCS class in terms of product performance and identify the practical gaps that must be filled to enable the classification system to be adopted into day-to-day practice. Consideration is given to the critical experimental data required and the methods for their generation with a focus on: (i) dose to the lungs, (ii) drug solubility in relevant media and methods to model the dissolution of respirable formulations, and (iii) pulmonary drug permeability. As described in three prior publications, the iBCS was developed to classify inhaled drugs based on physicochemical and biorelevant product attributes in a manner that will allow formulators and discovery chemists to identify and mitigate product development risks. It was not established to enable <i>in vitro</i> determination of bioequivalence between orally inhaled drug products. However, once analytical methods are in place to correctly classify inhaled drugs, the system has the potential to provide an understanding of the development risks associated with both establishing bioequivalence between two drug products and enabling postapproval changes based on product iBCS class.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1740-1751"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nonadiabatic Field: A Conceptually Novel Approach for Nonadiabatic Quantum Molecular Dynamics.","authors":"Baihua Wu, Bingqi Li, Xin He, Xiangsong Cheng, Jiajun Ren, Jian Liu","doi":"10.1021/acs.jctc.5c00181","DOIUrl":"https://doi.org/10.1021/acs.jctc.5c00181","url":null,"abstract":"<p><p>Reliable trajectory-based nonadiabatic quantum dynamics methods at the atomic/molecular level are critical for the practical understanding and rational design of many important processes in real large/complex systems, where the quantum dynamical behavior of electrons and that of nuclei are coupled. The paper reports latest progress of nonadiabatic field (NaF), a conceptually novel approach for nonadiabatic quantum dynamics with independent trajectories. Substantially different from the mainstreams of Ehrenfest-like dynamics and surface hopping methods, the nuclear force in NaF involves the nonadiabatic force arising from the nonadiabatic coupling between different electronic states, in addition to the adiabatic force contributed by a single adiabatic electronic state. NaF is capable of faithfully describing the interplay between electronic and nuclear motion in a broad regime, which covers where the relevant electronic states keep coupled in a wide range or all the time and where the bifurcation characteristic of nuclear motion is essential. NaF is derived from the exact generalized phase space formulation with coordinate-momentum variables, where constraint phase space (CPS) is employed for discrete electronic-state degrees of freedom (DOFs) and infinite Wigner phase space is used for continuous nuclear DOFs. We propose efficient integrators for the equations of motion of NaF in both adiabatic and diabatic representations. Since the formalism in the CPS formulation is not unique, NaF can in principle be implemented with various phase space representations of the time correlation function (TCF) for the time-dependent property. They are applied to a suite of representative gas-phase and condensed-phase benchmark models where numerically exact results are available for comparison. It is shown that NaF is relatively insensitive to the phase space representation of the electronic TCF and will be a potential tool for practical and reliable simulations of the quantum mechanical behavior of both electronic and nuclear dynamics of nonadiabatic transition processes in real systems.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junjie Zhang, Hui Yang, Liang Li, Changkun Peng, Jingying Li
{"title":"Noninvasive Transdermal Delivery of STING Agonists Reshapes the Immune Microenvironment of Melanoma and Potentiates Checkpoint Blockade Therapy Efficacy.","authors":"Junjie Zhang, Hui Yang, Liang Li, Changkun Peng, Jingying Li","doi":"10.1021/acsabm.4c02004","DOIUrl":"https://doi.org/10.1021/acsabm.4c02004","url":null,"abstract":"<p><p>The emergence of immunotherapy as a revolutionary therapeutic modality has fostered confidence and underscored its potent efficacy in tumor therapy. However, enhancing the therapeutic efficacy of immunotherapy by precise and judicious administration poses a significant challenge. In this context, we have developed a disulfide-bearing transdermal nanovaccine by integrating a thiol-reactive agent lipoic acid (LA) into a metal-coordinated cyclic dinucleotide nanoassembly, designated as LA-Mn-cGAMP (LMC) nanovaccines. Upon topical application to the skin with melanoma, the dithiolane moiety of LA enables thiol-disulfide dynamic exchange in the skin, hence facilitating penetration into both the skin and subcutaneous tumor tissues via the thiol-mediated uptake (TMU) mechanism. Our findings demonstrate that transdermal administration of LMC significantly enhances STING activation, mitigates the immunosuppressive tumor microenvironment (TME), and retards melanoma progression. Moreover, the remodeled TME amplifies the efficacy of immune checkpoint inhibitors. This advancement offers an administration strategy for existing STING agonist therapy, potentially improving the biosafety of immunotherapy.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomacromoleculesPub Date : 2025-04-07DOI: 10.1021/acs.biomac.4c01492
Beverly Chou, Rishad J Dalal, Kenneth J Shea
{"title":"Autonomous Abiotic Thermal Protectant for Immunoglobulin G: Reducing the Need for Cold Chain Storage.","authors":"Beverly Chou, Rishad J Dalal, Kenneth J Shea","doi":"10.1021/acs.biomac.4c01492","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01492","url":null,"abstract":"<p><p>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 (<i>T</i><sub>m</sub>), 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 <i>T</i><sub>m</sub>. 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.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}