ACS Applied Bio Materials最新文献

{"title":"Column Chromatography-Free Synthesis of Spirooxindole and Spiroindanone-Based Naphthalimides as Potent <i>c-MYC</i> G4 Stabilizers and HSA Binders for Elevating Anticancer Potential.","authors":"Anmol Jain, Kamaldeep Paul","doi":"10.1021/acsabm.4c01726","DOIUrl":"10.1021/acsabm.4c01726","url":null,"abstract":"<p><p>G-quadruplex (G4) DNA plays a pivotal regulatory role in fundamental biological processes, integral for governing cellular functions such as replication, transcription, and repair in living cells. Within cancer cells, G4 DNA exerts an impact on the expression of crucial genes such as <i>c-MYC</i>, effectively repressing its activity when structured within its promoter region. Therefore, employing molecular scaffolds to target these structures offers an attractive strategy for altering their functions. In our pursuit of potent and selective G-quadruplex binders, herein we report a series of spironaphthalimide-pyrrolidine analogues that demonstrate the ability to stabilize <i>c-MYC</i> G4 formation and subsequently inhibit <i>c-MYC</i> expression. These analogues are evaluated for their anticancer activity against 60 human cancer cell lines at 10 μM. The most potent analogues <b>8j</b> and <b>21c</b> underwent additional testing at five dose concentrations (10^-4-10^-8 M) where low MG-MID GI₅₀ values are observed for both the analogues <b>8j</b> (9.98 μM) and <b>21c</b> (2.49 μM). To correlate with the antiproliferative activity, the mechanism is explored in vitro by performing <i>Pu</i>27 DNA binding studies through multispectroscopic techniques, and the results are compared with <i>Pu</i>22, human telomere, and calf thymus DNA. Additionally, insights from molecular docking suggested stacking over the G-tetrad of G4 structures of both analogues, with quantum mechanical studies further reinforcing the rationale for the stability of this quadruplex secondary structure. The analogues are also evaluated for their binding affinity to human serum albumin, revealing their robust capability to effectively bind and potentially facilitate targeted delivery to specific sites. Amidst the abundance of G4s across the human genome, the above findings underscore the significance of spiro analogues, with potent multitargeting anticancer attributes, marking a transformative leap forward in G4-ligand innovation, promising frontiers in the quest for effective anticancer modalities.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"3728-3747"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254003","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}

{"title":"Enhancing the Reactivity of Nanozymes by Asymmetric Structural Oxygen Vacancy Electron Transfer for Colorimetric Sensing and TAC Analysis.","authors":"Lishi Chen, Pingfei Wang, Ao Yin, Liang Zhuang, Shan He, Guiju Zhang, Bao-Cai Xu","doi":"10.1021/acsabm.5c00244","DOIUrl":"10.1021/acsabm.5c00244","url":null,"abstract":"<p><p>By regulating the electron density of atoms within the reaction active center, the catalytic activity of nanozymes can be precisely controlled, thereby enhancing their reactivity and sensitivity in applications such as colorimetric sensing. In this study, we synthesized metal oxide Fe-MMO<i>_ov</i> nanozymes, enriched with doping defects and oxygen vacancy defects, by Fe-doped LDH with an ultrathin 2D structure through roasting-induced topological transformation. This process tunes the electron density distribution within the active center atoms of the nanozymes through its intrinsic asymmetric Zn-O<i>_v</i>-Fe doping structure, resulting in excellent POD-like and OXD-like multienzyme activities. This enhancement contributes to the overall effectiveness of nanozymes in applications such as colorimetry. These improvements facilitated its successful application in the total antioxidant capacity (TAC) detection of various fruit juices and commercial beverages. Density functional theory (DFT) calculations revealed that the d-band center of the Fe active center is enhanced by the O<i>_v</i> microenvironment within the Fe-MMO<i>_ov</i> nanozyme, leading to improved catalytic activity. Based on this, a Fe-MMO<i>_ov</i>/TMB visual colorimetric system was established and successfully validated for colorimetric detection of analytes such as ascorbic acid, cysteine, and glutathione. It was further integrated with a mobile platform for on-site TAC detection in food samples. This study introduces an approach for nanozyme design in colorimetric sensing while also presenting a rapid, cost-effective, and dependable strategy for the miniaturization, convenience, and widespread applicability of TAC detection. We demonstrate how the introduction of oxygen vacancies into Fe-MMO<i>_ov</i> nanozymes enhances their catalytic activity, paving the way for the development of more efficient catalysts in colorimetric detection.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"4073-4083"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950716","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}

{"title":"Virus Detection by CRISPR-Cas9-Mediated Strand Displacement in a Lateral Flow Assay.","authors":"Roser Montagud-Martínez, Rosa Márquez-Costa, Raúl Ruiz, Adrià Martínez-Aviñó, Rafael Ballesteros-Garrido, David Navarro, Pilar Campins-Falcó, Guillermo Rodrigo","doi":"10.1021/acsabm.5c00307","DOIUrl":"10.1021/acsabm.5c00307","url":null,"abstract":"<p><p>In public health emergencies or in resource-constrained settings, laboratory-based diagnostic methods, such as RT-qPCR, need to be complemented with accurate, rapid, and accessible approaches to increase testing capacity, as this will translate into better outcomes in disease prevention and management. Here, we develop an original nucleic acid detection platform by leveraging CRISPR-Cas9 and lateral flow immunochromatography technologies. In combination with an isothermal amplification that runs with a biotinylated primer, the system exploits the interaction between the CRISPR-Cas9 R-loop formed upon targeting a specific nucleic acid and a fluorescein-labeled probe to generate a visual readout on a lateral flow device. Our method enables rapid, sensitive detection of nucleic acids, achieving a limit of 1-10 copies/μL in 1 h at a low temperature. We validated the efficacy of the method by using clinical samples of patients infected with SARS-CoV-2. Compared with other assays, it operates with more accessible molecular elements and showcases a robust signal-to-noise ratio. Moreover, multiplexed detection was demonstrated using primers labeled with biotin and digoxigenin, achieving the simultaneous identification of target genes on lateral flow devices with two test lines. We successfully detected SARS-CoV-2 and Influenza A (H1N1) in spiked samples, highlighting the potential of the method for multiplexed diagnostics of respiratory viruses. All in all, this represents a versatile and manageable platform for point-of-care testing, thereby supporting better patient outcomes and enhanced pandemic preparedness.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"4221-4229"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Repurposing: Unique Carbon Dot Antibacterial Films for Fruit Postharvest Preservation.","authors":"Xinyu Liu, Haobin Wang, Jie Li, Jianan Xu, Yanhong Li, Chunyuan Tian, Lijun Zhao, Feng Luan, Tao He, Weijian Liu, Mingle Li, Xuming Zhuang, Chao Shi, Xiaojun Peng","doi":"10.1021/acsabm.5c00362","DOIUrl":"10.1021/acsabm.5c00362","url":null,"abstract":"<p><p>Fruit spoilage caused by oxidation and microbial infection exacerbates resource wastage. Although starch films including chitosan possessed admirable biocompatibility owing to great biodegradability compared with conventional plastics, deficient antibacterial and antioxidant capacity restricted food shelf life. Herein, an environmentally friendly antibacterial film (CS/G-CDs) was constructed by carbon dots derived from <i>Cirsii Herba</i> (CDs), which was formed through high affinity resulting from hydrogen bonding between chitosan molecules and hydroxyl originating from CDs. The prepared CDs presented homogeneous and monodisperse spherical structures with an ultrasmall size, providing favorable conditions for uniform film formation. Encouragingly, the antioxidant capacity of CS/G-CDs increased 5.00-fold, followed by an antibacterial rate of up to 97.0%. Dramatically, CS/G-CDs revealed glorious UV shielding efficacy (99.9% for UVB and 98.2% for UVA), and its preservation time for blueberries was remarkably extended 8 days longer than that of the chitosan film. Overall, Chinese herb-derived antibacterial films exhibited magnified antibacterial/antioxidant properties and great biocompatibility, which provided a promising strategy for sustainable development of packaging materials.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"4239-4250"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950759","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}

{"title":"Evaluation of mRNA Transfection Reagents for mRNA Delivery and Vaccine Efficacy via Intramuscular Injection in Mice.","authors":"Jungho Kim, Jihyun Yang, Suhyeon Heo, Haryoung Poo","doi":"10.1021/acsabm.5c00424","DOIUrl":"10.1021/acsabm.5c00424","url":null,"abstract":"<p><p>The selection of an effective delivery carrier is crucial to assessing mRNA-based vaccines and therapeutics <i>in vivo</i>. Although lipid nanoparticles (LNPs) are commonly used for mRNA delivery, the LNP-mRNA formulation process is laborious and time-consuming and requires a high-cost microfluidic device. Instead, mixing with commercial reagents may simplify mRNA transfection into cells. However, their potential as <i>in vivo</i> carriers in intramuscular vaccination in mouse models remains unclear. In this study, we used three types of commercial RNA transfection reagents, MessengerMAX (MAX; liposome), TransIT-mRNA (IT; cationic polymer), and Invivofectamine (IVF; LNP), to produce nanoparticles directly by pipetting. The particle characteristics and mRNA delivery efficacy of the mRNA-transfection reagent mixtures were analyzed. Additionally, immune responses to vaccine efficacy and protective immunity of the mRNA mixtures as vaccine antigens were evaluated in a mouse model. Although MAX and IT showed high <i>in vitro</i> transfection efficiencies, their <i>in vivo</i> performances were limited. In contrast, IVF exhibited notable particle stability and homogeneity, making it a promising delivery carrier. Intramuscular IVF injection significantly enhanced both innate and adaptive immune responses with a robust systemic protein expression. Notably, when using SARS-CoV-2 Spike mRNA, IVF showed robust humoral immune responses, including production of IgG and neutralizing antibodies, thereby resulting in complete protection against SARS-CoV-2 infection. Therefore, these findings position IVF as an accessible and efficient mRNA carrier for evaluating mRNA vaccines and therapeutic efficacy in basic research.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"4315-4324"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950795","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}

{"title":"Ultrahigh Dispersion of Fe₃O₄ NPs on Cellulose Nanofibers: Unlocking Superior Visible-Light Photocatalysis.","authors":"Iqra Rabani, Ghulam Dastgeer, Hai Bang Truong, Mu Naushad, Nguyen Tien Tran, Young-Soo Seo","doi":"10.1021/acsabm.5c00303","DOIUrl":"10.1021/acsabm.5c00303","url":null,"abstract":"<p><p>Constructing cost-effective and efficient photocatalysts is crucial for removing harmful contaminants from water sources, ensuring a greener and healthier environment. In this study, highly dispersed magnetic iron oxide (Fe₃O₄) nanoparticles (NPs) were successfully decorated on cellulose nanofibers (CNFs) by using a simple interfacial strategy. Four hybrid materials (Fe₃O₄-CNF1, Fe₃O₄-CNF2, Fe₃O₄-CNF3, and Fe₃O₄-CNF4) were systematically synthesized, with Fe₃O₄-CNF4 identified as the most efficient photocatalyst. The optimized Fe₃O₄-CNF4 hybrid exhibited a high surface area (54.12 m²/g), enhanced light utilization, and improved charge separation, leading to superior photocatalytic performance. It achieved a 95% removal rate of Rhodamine B (RhB) in 120 min and 99% removal rate of Methylene Blue (MB) in 150 min when exposed to visible irradiation. Moreover, Fe₃O₄-CNF4 demonstrated excellent recyclability, maintaining high efficiency over five reuse cycles with only ∼7% activity loss. Stability tests under varying catalyst concentrations and pH conditions further confirmed its robustness. Additionally, the primary active species, potential degradation pathways of MB, and the underlying reaction mechanism were systematically analyzed. These findings highlight Fe₃O₄-CNF4 as a promising visible-light-responsive and reusable photocatalyst for wastewater treatment.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"4209-4220"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950887","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}

{"title":"Magnesium Ion/Gallic Acid MOF-Laden Multifunctional Acellular Matrix Hydrogels for Diabetic Wound Healing.","authors":"Lutong Liu, Zhaozhao Ding, Yong Huang, Junwei Zou","doi":"10.1021/acsabm.4c01979","DOIUrl":"10.1021/acsabm.4c01979","url":null,"abstract":"<p><p>The main objective for diabetic wound treatment is the design of a functional dressing that scavenges free radicals, alleviates inflammation, and is antibacterial while promoting neovascularization. Herein, a multifunctional acellular matrix hydrogel was prepared with the antimicrobial peptide jelleine-1 and a magnesium ion/gallic acid metal framework to exhibit antioxidant, anti-inflammatory, and proangiogenesis effects in diabetic wounds. The prepared hydrogel termed Gel-J-MOF efficiently released gallic acid in the acidic microenvironment of the diabetic wound, scavenged excess free radicals in vitro, and effectively reduced the levels of inflammation by regulating M2 macrophage polarization in vivo. The antimicrobial peptide jelleine-1 in the composite hydrogel effectively inhibited <i>S. aureus</i> and <i>E. coli</i> in vitro, promoting a suitable microenvironment for wound healing. In the later stage of wound healing, the composite hydrogel stimulated angiogenesis, accelerating the re-epithelialization and collagen deposition in the wound. In conclusion, this multifunctional composite hydrogel provides a regulated microenvironment for treating diabetic wounds and, therefore, has significant potential application promise in the treatment of chronic diabetic wounds.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"3811-3823"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950925","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}

{"title":"Enhanced Intracellular IR780 Delivery by Acidity-Triggered PEG-Detachable Hybrid Nanoparticles to Augment Photodynamic and Photothermal Combination Therapy for Melanoma Treatment.","authors":"Min-Chen Tsai, Lun-Yuan Hsiao, Yen-Hsuan Chang, Yu-Hsin Chen, Shang-Hsiu Hu, Chun-Yu Hung, Wen-Hsuan Chiang","doi":"10.1021/acsabm.5c00144","DOIUrl":"10.1021/acsabm.5c00144","url":null,"abstract":"<p><p>The PEGylation of drug-carrying nanoparticles has often been used to prolong blood circulation and improve drug deposition at tumor sites. Nevertheless, the PEG-rich hydrophilic surfaces retard the release of the payloads and internalization of therapeutic nanoparticles by cancer cells, thus lowering the anticancer efficacy. To boost the anticancer potency of the combined photodynamic therapy (PDT) and photothermal therapy (PTT) against melanoma by conquering the PEG dilemma, herein, the hybrid PEGylated chitosan-covered polydopamine (PDA) nanoparticles (PCPNs) with acidity-elicited PEG detachment ability were fabricated as carriers of IR780, a small-molecule photosensitizer used for PTT and PDT. The IR780@PCPNs displayed a uniform, solid-like spherical shape and sound colloidal stability. Under near-infrared (NIR) irradiation, the IR780@PCPNs showed prominent photothermal conversion efficiency (ca. 54.6%), robust photothermal stability, reduced IR780 photobleaching, sufficient singlet oxygen (¹O₂) production, and glutathione-depleting ability. Moreover, with the environmental pH being reduced from 7.4 to 5.0 at 37 °C, the decreased interactions between IR780 and PCPNs due to the increased protonation of phenolic hydroxyl residues within PDA and primary amine groups of chitosan accelerated the release of IR780 species from IR780@PCPNs. Importantly, the cellular uptake of IR780@PCPNs by B16F10 melanoma was remarkably promoted in a weakly acidic milieu upon PEG detachment driven by the disintegration of acid-labile benzoic imine. With NIR irradiation, the internalized IR780@PCPNs generated hyperthermia and ¹O₂ to damage mitochondria, thereby effectively inhibiting the proliferation of B16F10 cells. Collectively, our findings present a practical strategy for amplifying the anticancer efficacy of PTT combined with PDT using PEG-detachable IR780@PCPNs.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"3995-4007"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Effect of Dexamethasone Delivery on Osteogenic Differentiation of MC3T3-E1 Cells in a Mineralized Hydrogel Microenvironment.","authors":"Hareet Singh Channey, Ketki Holkar, Vaijayanti Kale, Ganesh Ingavle","doi":"10.1021/acsabm.5c00345","DOIUrl":"https://doi.org/10.1021/acsabm.5c00345","url":null,"abstract":"<p><p>The current traditional approaches, such as autografts, allografts, and metal implants, for healing fractures with critical size defects have numerous disadvantages. These disadvantages highlight the necessity of bone tissue engineering (BTE) in modern times. The delivery of bioactive molecules offers several clear advantages for enhancing cellular functions during BTE. This study presents a BTE strategy by integrating a mineralized alginate hydrogel with the sustained release of dexamethasone (DEX). Nanohydroxyapatite (nHAp) was incorporated to create a mineralized microenvironment that enhances osteoconductivity, while poly(lactide-co-glycolide) (PLGA) microspheres (PLGA-MS) were used for the controlled delivery of DEX, ensuring continuous osteoinductive signaling. The physical characterization of the alginate hydrogel scaffold was performed, including swelling degree measurement, stability assessment using rheometric analysis, degradability, and evaluation of the porous surface structure using field emission scanning electron microscopy. The scaffold's surface area was estimated by Brunauer-Emmett-Teller (BET) analysis, and FTIR confirmed DEX incorporation into PLGA-MS. - To identify the optimal DEX concentration for promoting osteogenesis, 3D alginate hydrogel models were tested using 0.05, 0.1 and 1 mg/mL. Cell viability assay, alkaline phosphatase (ALP) activity, and DNA content were evaluated. The results indicated that 0.1 mg/mL DEX had the highest normalized ALP content and minimal cytotoxicity; hence, it was chosen for the next phase of this study. Further, an effective delivery system for DEX, utilized both direct and sustained release within mineralized alginate, was evaluated to assess its osteoinductive potential. The results of this study indicated that the sustained delivery of DEX was the most effective for BTE applications due to its high osteogenic potential, as evidenced by increased normalized ALP activity and enhanced bone mineralization, indicated by a higher calcium content. The drug release patterns were also studied, and the results showed a 72% cumulative release in the PLGA-DEX group after 14 days. The system utilized an injectable alginate hydrogel forminimally invasive delivery and employed a 3D culture model that more accurately replicates the <i>in vivo</i> bone environment compared to traditional 2D systems. This comprehensive approach achieved dual functionality by promoting osteogenesis while simultaneously providing anti-inflammatory effects, thereby addressing key challenges in bone repair and offering a promising solution for improved bone regeneration.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091965","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}

{"title":"Cyclic Acetal-Based Lipid Nanoparticles Deliver mRNA In Vivo for Tumor Immunotherapy.","authors":"Honglei Zhang, Yizi Zhu, Jingxuan Ma, Yuqing Ma, Lijie Jin, Jing Li, Rui Yang, Gengshen Song","doi":"10.1021/acsabm.5c00076","DOIUrl":"10.1021/acsabm.5c00076","url":null,"abstract":"<p><p>Lipid nanoparticle (LNP)-mRNA-based tumor immunotherapy needs to address challenges such as low efficacy of mRNA delivery, targeted protein expression, and compromised innate immunogenicity. Here, we screen a panel of 16 cyclic acetal-based ionizable lipid nanoparticles by in vitro and in vivo assays to develop a more effective and safer system specifically for tumor immunotherapy and mRNA delivery. Furthermore, by incorporating a cyclic acetal-based adjuvant lipid YK-TLR-001, two optimized cyclic acetal-based LNP formulations (YK-712 and YK-716) are demonstrated to enhance mRNA expression in the spleens and to induce exceptional maturation of antigen-presenting cells (APCs) and to promote antigen presentation. Moreover, animal studies treated with these formulations show activated cellular immunogenicity in healthy mice and inhibited tumor growth in the B16F10 melanoma model. Thus, the cyclic acetal-based LNPs with YK-TLR-001 present a promising direction in the design of mRNA vectors for the advancement of mRNA tumor immunotherapy.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"3888-3898"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950635","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}