Pub Date : 2026-03-01DOI: 10.1016/j.apsb.2026.02.024
Ruizhe Xu, Xuejing Li, Xiaomin Su, Xifeng Qin, Ying He, Siyu Wang, Yue Liu (292931), Jiayi Wu, Ting Wang, Mingyang Liu, Boshu Ouyang, Jia Li (160557), Wuli Yang, Bo Zhang, Hei Chen
The efficient targeted delivery and on-demand release of nanomedicines still present significant challenges in tumor therapy. In the present study, we developed a novel strategy of tumor ferroptosis therapy through the synergistic effect of nanomedicines (biomimetic liposomes) and a medical device (high-intensity focused ultrasound, HIFU). It was found that HIFU irradiation induced heightened expressions of CD44 and reactive oxygen species (ROS) in tumor cells by 1.43-fold and 2.64-fold, respectively. This allowed the gambogic acid-loaded, platelet-mimicking liposomes (PLip) to more precisely target the tumor cells through the interaction of CD44 and P-selectin on the PLip and subsequently ROS-responsively release the drug from PLip, thus effectively killing tumor cells. Crucially, gambogic acid also significantly enhanced ROS production, leading to lipid peroxidation and augmented ferroptosis induced by HIFU. In summary, HIFU demonstrates immense potential in synergizing with nanomedicines to combat tumors. HIFU upregulated CD44 and ROS, enabling platelet-mimicking liposomes to target tumors and release gambogic acid, enhancing lipid peroxidation and ferroptosis, demonstrating synergistic nanomedicine-device tumor therapy potential.
{"title":"Biomimetic liposomes synergize with high-intensity focused ultrasound to induce ferroptosis in tumors","authors":"Ruizhe Xu, Xuejing Li, Xiaomin Su, Xifeng Qin, Ying He, Siyu Wang, Yue Liu (292931), Jiayi Wu, Ting Wang, Mingyang Liu, Boshu Ouyang, Jia Li (160557), Wuli Yang, Bo Zhang, Hei Chen","doi":"10.1016/j.apsb.2026.02.024","DOIUrl":"https://doi.org/10.1016/j.apsb.2026.02.024","url":null,"abstract":"The efficient targeted delivery and on-demand release of nanomedicines still present significant challenges in tumor therapy. In the present study, we developed a novel strategy of tumor ferroptosis therapy through the synergistic effect of nanomedicines (biomimetic liposomes) and a medical device (high-intensity focused ultrasound, HIFU). It was found that HIFU irradiation induced heightened expressions of CD44 and reactive oxygen species (ROS) in tumor cells by 1.43-fold and 2.64-fold, respectively. This allowed the gambogic acid-loaded, platelet-mimicking liposomes (PLip) to more precisely target the tumor cells through the interaction of CD44 and P-selectin on the PLip and subsequently ROS-responsively release the drug from PLip, thus effectively killing tumor cells. Crucially, gambogic acid also significantly enhanced ROS production, leading to lipid peroxidation and augmented ferroptosis induced by HIFU. In summary, HIFU demonstrates immense potential in synergizing with nanomedicines to combat tumors. HIFU upregulated CD44 and ROS, enabling platelet-mimicking liposomes to target tumors and release gambogic acid, enhancing lipid peroxidation and ferroptosis, demonstrating synergistic nanomedicine-device tumor therapy potential.","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-01DOI: 10.1016/j.apsb.2025.10.045
Huanyu Hong , Mengchao Xiao , Hui Qian , Siqi Tan , Sihan Wu , Fang Liu , Xialu Hong , Shuqing Liu , Chenhong Ding , Keqi Wang , Weifen Xie , Xin Zhang
Previous studies have highlighted the downregulation of hepatocyte nuclear factor 4alpha (HNF4α) as a critical event in the pathogenesis of HCC. However, the mechanism of its degradation in HCC remains unclear. Tripartite motif 47 (TRIM47), a typical E3 ubiquitin ligase of the TRIM family, has been implicated in various tumors, yet its specific role in HCC progression is not fully elucidated. In this study, HNF4α was identified as a potential target of TRIM47 by using co-immunoprecipitation (Co-IP) combined with mass spectrometry analysis. TRIM47 facilitates the degradation of HNF4α by mediating K48-linked ubiquitination at lysine 470. Abrogation of HNF4α ubiquitination attenuated the promoting effect of TRIM47 on HCC malignancy. Molecular docking studies and Co-IP experiments revealed that K342, W349, and E353 of HNF4α, along with K534 and K600 of TRIM47, are crucial for their interaction. A small molecule, CZ-2401, was selected as a potent inhibitor of the TRIM47–HNF4α interaction through virtual screening and pharmacological activity validation. CZ-2401 effectively stabilizes HNF4α protein in HCC cells and ameliorates TRIM47-driven HCC progression in vivo. Taken together, our research elucidates that targeting TRIM47–HNF4α interaction is a potential therapeutic strategy for HCC, and identifies CZ-2401 as a potent inhibitor of HNF4α degradation and a promising candidate for HCC therapy.
{"title":"Blocking TRIM47-mediated HNF4α degradation suppresses hepatocellular carcinoma progression","authors":"Huanyu Hong , Mengchao Xiao , Hui Qian , Siqi Tan , Sihan Wu , Fang Liu , Xialu Hong , Shuqing Liu , Chenhong Ding , Keqi Wang , Weifen Xie , Xin Zhang","doi":"10.1016/j.apsb.2025.10.045","DOIUrl":"10.1016/j.apsb.2025.10.045","url":null,"abstract":"<div><div>Previous studies have highlighted the downregulation of hepatocyte nuclear factor 4alpha (HNF4<em>α</em>) as a critical event in the pathogenesis of HCC. However, the mechanism of its degradation in HCC remains unclear. Tripartite motif 47 (TRIM47), a typical E3 ubiquitin ligase of the TRIM family, has been implicated in various tumors, yet its specific role in HCC progression is not fully elucidated. In this study, HNF4<em>α</em> was identified as a potential target of TRIM47 by using co-immunoprecipitation (Co-IP) combined with mass spectrometry analysis. TRIM47 facilitates the degradation of HNF4<em>α</em> by mediating K48-linked ubiquitination at lysine 470. Abrogation of HNF4<em>α</em> ubiquitination attenuated the promoting effect of TRIM47 on HCC malignancy. Molecular docking studies and Co-IP experiments revealed that K342, W349, and E353 of HNF4<em>α</em>, along with K534 and K600 of TRIM47, are crucial for their interaction. A small molecule, CZ-2401, was selected as a potent inhibitor of the TRIM47–HNF4<em>α</em> interaction through virtual screening and pharmacological activity validation. CZ-2401 effectively stabilizes HNF4<em>α</em> protein in HCC cells and ameliorates TRIM47-driven HCC progression <em>in vivo.</em> Taken together, our research elucidates that targeting TRIM47–HNF4<em>α</em> interaction is a potential therapeutic strategy for HCC, and identifies CZ-2401 as a potent inhibitor of HNF4<em>α</em> degradation and a promising candidate for HCC therapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 2","pages":"Pages 913-929"},"PeriodicalIF":14.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-12DOI: 10.1016/j.apsb.2025.11.006
Yu Wen , Tian Yang , Qi Li , Xiaosi Li , Xiaoyan Ma , Huiyang Hu , Prabhakar Busa , Sayma Alam , Libo Tan , Chao Zhao
Perineurally injected nerve-blocking agents have limited capability to cross peripheral nerve barriers (PNBs), requiring high doses to block pain signals on axons. This increases the risk of local tissue toxicity and systemic side effects on the cardiovascular and neurological systems. To address this, we explored carboxyl group modification to enhance the permeability of nerve-blocking agents across the PNBs through carrier-mediated transport facilitated by monocarboxylate transporters (MCTs). The enhanced permeability allows for targeted drug delivery to peripheral nerve axons, resulting in a significant reduction in the necessary drug dosage for a long-lasting nerve block. Specifically, we developed a carboxylated prodrug of capsaicin (COOH-CAP) by conjugating it with a carboxyl group via a degradable ester bond. Calcium flux assays, patch-clamp recordings, and body temperature measurements collectively confirmed that COOH-CAP activates TRPV1, with potency comparable to capsaicin. In rats, a single sciatic nerve injection of 3.28 μmol COOH-CAP produced a nociceptive-selective nerve blockade lasting 260 ± 83.7 h without motor impairment or capsaicin-related side effects, approximately 35 times longer than the same dose of plain capsaicin. Even at a lower dose of 1.64 μmol, COOH-CAP still produced nociceptive-selective nerve blockade for 172.0 ± 41.3 h.
{"title":"Carboxylated prodrug of capsaicin with enhanced peripheral nerve permeation mediated by monocarboxylate transporters for long-lasting local anesthesia","authors":"Yu Wen , Tian Yang , Qi Li , Xiaosi Li , Xiaoyan Ma , Huiyang Hu , Prabhakar Busa , Sayma Alam , Libo Tan , Chao Zhao","doi":"10.1016/j.apsb.2025.11.006","DOIUrl":"10.1016/j.apsb.2025.11.006","url":null,"abstract":"<div><div>Perineurally injected nerve-blocking agents have limited capability to cross peripheral nerve barriers (PNBs), requiring high doses to block pain signals on axons. This increases the risk of local tissue toxicity and systemic side effects on the cardiovascular and neurological systems. To address this, we explored carboxyl group modification to enhance the permeability of nerve-blocking agents across the PNBs through carrier-mediated transport facilitated by monocarboxylate transporters (MCTs). The enhanced permeability allows for targeted drug delivery to peripheral nerve axons, resulting in a significant reduction in the necessary drug dosage for a long-lasting nerve block. Specifically, we developed a carboxylated prodrug of capsaicin (COOH-CAP) by conjugating it with a carboxyl group <em>via</em> a degradable ester bond. Calcium flux assays, patch-clamp recordings, and body temperature measurements collectively confirmed that COOH-CAP activates TRPV1, with potency comparable to capsaicin. In rats, a single sciatic nerve injection of 3.28 μmol COOH-CAP produced a nociceptive-selective nerve blockade lasting 260 ± 83.7 h without motor impairment or capsaicin-related side effects, approximately 35 times longer than the same dose of plain capsaicin. Even at a lower dose of 1.64 μmol, COOH-CAP still produced nociceptive-selective nerve blockade for 172.0 ± 41.3 h.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 2","pages":"Pages 994-1008"},"PeriodicalIF":14.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-02-05DOI: 10.1016/j.apsb.2026.01.011
Wei Wei
{"title":"A new paradigm for treating lung cancer by targeting the intratumoral microbiome","authors":"Wei Wei","doi":"10.1016/j.apsb.2026.01.011","DOIUrl":"10.1016/j.apsb.2026.01.011","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 2","pages":"Pages 1168-1169"},"PeriodicalIF":14.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-26DOI: 10.1016/j.apsb.2025.11.027
Hanlu Wang , Tiantian Yang , Yichao Yan , Fengmei Yang , Xunhuan Song , Shuning Zhang , Wenhong Jiang , Mingxue Li , Wenting Sun , Yanyan Li , Weihua Jin , Suqin Duan , Meng Qin , Zhanlong He , Yongping Jiang
COVID-19 and its variants have spread around the world, triggering a range of long-term sequelae and leading to the need for broadly effective vaccines. We have established a new fusion protein combining the receptor-binding domain region (SF2) and a newly identified conserved binding region (SF5) from the spike of SARS-CoV-2. This fusion protein (COVID19-SF2+SF5) specifically bound to VERO-E6 cells with higher efficiency than either region alone. Antibodies raised in mice against COVID19-SF2+SF5 cross-reacted with every fragment of SARS-CoV-2 and SARS. Additionally, antibodies against the fusion protein effectively neutralize pseudoviruses of both wild-type and mutant strains of SARS-CoV-2 (including BA.3, XBB.1.5, and EG.5), as well as SARS pseudoviruses. Protein interaction prediction and binding affinity determination revealed that the fusion protein exhibits strong binding capacity to three key host molecules: heparan sulfate proteoglycan (HSPG), neuropilin-1 (NRP1), and cluster of differentiation 147 (CD147). Analysis of representative viruses from four coronavirus genera (α, β, γ, δ)—including 229E, NL63, OC43, HKU1, SARS-CoV, MERS-CoV, HKU20, and IBV—revealed that these coronaviruses share sequence similarity mainly on SF2 and SF5 regions. Furthermore, immunization of female hamsters with COVID19-SF2+SF5 provided significant protection against a SARS-CoV-2 virus challenge. Taken together, our results indicate that vaccination with a protein containing both an receptor binding domain (RBD) region and a common binding region provides strong protection during infection, thus suggesting a potential strategy to avoid evasion of host immune recognition by virus variants. Significantly, the observation that COVID19-SF2+SF5 immunization possesses stronger activity in reducing viral load at early stages suggests that the SF5 region might play an important role in virus recognition and binding to host cells. Based on these findings, we conclude that it is possible to develop universal vaccines and neutralizing monoclonal antibodies to curb the effects of mutations and to target multiple coronaviruses.
{"title":"A novel fusion protein of COVID-19 virus enhancing protection of Syrian hamsters infected with SARS-CoV-2","authors":"Hanlu Wang , Tiantian Yang , Yichao Yan , Fengmei Yang , Xunhuan Song , Shuning Zhang , Wenhong Jiang , Mingxue Li , Wenting Sun , Yanyan Li , Weihua Jin , Suqin Duan , Meng Qin , Zhanlong He , Yongping Jiang","doi":"10.1016/j.apsb.2025.11.027","DOIUrl":"10.1016/j.apsb.2025.11.027","url":null,"abstract":"<div><div>COVID-19 and its variants have spread around the world, triggering a range of long-term sequelae and leading to the need for broadly effective vaccines. We have established a new fusion protein combining the receptor-binding domain region (SF2) and a newly identified conserved binding region (SF5) from the spike of SARS-CoV-2. This fusion protein (COVID19-SF2+SF5) specifically bound to VERO-E6 cells with higher efficiency than either region alone. Antibodies raised in mice against COVID19-SF2+SF5 cross-reacted with every fragment of SARS-CoV-2 and SARS. Additionally, antibodies against the fusion protein effectively neutralize pseudoviruses of both wild-type and mutant strains of SARS-CoV-2 (including BA.3, XBB.1.5, and EG.5), as well as SARS pseudoviruses. Protein interaction prediction and binding affinity determination revealed that the fusion protein exhibits strong binding capacity to three key host molecules: heparan sulfate proteoglycan (HSPG), neuropilin-1 (NRP1), and cluster of differentiation 147 (CD147). Analysis of representative viruses from four coronavirus genera (<em>α</em>, <em>β</em>, <em>γ</em>, <em>δ</em>)—including 229E, NL63, OC43, HKU1, SARS-CoV, MERS-CoV, HKU20, and IBV—revealed that these coronaviruses share sequence similarity mainly on SF2 and SF5 regions. Furthermore, immunization of female hamsters with COVID19-SF2+SF5 provided significant protection against a SARS-CoV-2 virus challenge. Taken together, our results indicate that vaccination with a protein containing both an receptor binding domain (RBD) region and a common binding region provides strong protection during infection, thus suggesting a potential strategy to avoid evasion of host immune recognition by virus variants. Significantly, the observation that COVID19-SF2+SF5 immunization possesses stronger activity in reducing viral load at early stages suggests that the SF5 region might play an important role in virus recognition and binding to host cells. Based on these findings, we conclude that it is possible to develop universal vaccines and neutralizing monoclonal antibodies to curb the effects of mutations and to target multiple coronaviruses.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 2","pages":"Pages 900-912"},"PeriodicalIF":14.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-19DOI: 10.1016/j.apsb.2025.11.022
Danfeng Wang , Wenjian Min , Binjian Jiang , Haopeng Sun , Chengliang Sun , Peng Yang
Deubiquitinase-targeting chimeras (DUBTAC), as a highly promising emerging technology, can precisely remove ubiquitin chains from target proteins by recruiting deubiquitinases (DUBs), thereby enhancing the stability of the target proteins. Multiple functional proteins, such as the tumor suppressor proteins p53, RB, PTEN, upon stabilization by DUBTAC, can effectively restore or enhance their physiological functions, thus achieving therapeutic effects. Currently, the DUBTAC technology is still in its early stage of development, yet it has broad application prospects and represents a technological approach for developing various “undruggable” targets. This article delves into the design strategy of DUBTAC, and screens and recommends some candidate proteins with the potential to serve as drug targets. We aim to provide perspective in drug design, structural optimization, target selection, and related aspects.
{"title":"From concept to application: Exploring the evolution and potential of DUBTAC technology","authors":"Danfeng Wang , Wenjian Min , Binjian Jiang , Haopeng Sun , Chengliang Sun , Peng Yang","doi":"10.1016/j.apsb.2025.11.022","DOIUrl":"10.1016/j.apsb.2025.11.022","url":null,"abstract":"<div><div>Deubiquitinase-targeting chimeras (DUBTAC), as a highly promising emerging technology, can precisely remove ubiquitin chains from target proteins by recruiting deubiquitinases (DUBs), thereby enhancing the stability of the target proteins. Multiple functional proteins, such as the tumor suppressor proteins p53, RB, PTEN, upon stabilization by DUBTAC, can effectively restore or enhance their physiological functions, thus achieving therapeutic effects. Currently, the DUBTAC technology is still in its early stage of development, yet it has broad application prospects and represents a technological approach for developing various “undruggable” targets. This article delves into the design strategy of DUBTAC, and screens and recommends some candidate proteins with the potential to serve as drug targets. We aim to provide perspective in drug design, structural optimization, target selection, and related aspects.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 2","pages":"Pages 770-787"},"PeriodicalIF":14.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-13DOI: 10.1016/j.apsb.2025.11.009
Caixia Tan, Ming Yan, Xinping Luo, Honghao Sun, Zhanwei Zhou, Minjie Sun
The mild photothermal therapy of solid tumors was still bottlenecked by the uneven temperature distribution in tumor tissue and the autophagy-mediated resistance. Here, we leveraged the ultra-small size (approximately 0.32 nm) and autophagy inhibitory property of nitric oxide (NO) to overcome these limitations for enhanced gas-photothermal therapy of large tumors. An NO donor was loaded into mesoporous polydopamine and coated with tumor cell membranes for tumor-targeting delivery. The acid-triggered release of NO potently inhibited autophagy to block the pro-survival pathway of tumor cells. Besides, as a small-molecule gas, it diffused freely into deep regions and precisely eliminated the deep-seated tumor cells, resulting in approximately 90% tumor inhibition in the late-stage breast tumor model (>500 mm3). The NO gas therapy shows great potential for complementing other therapeutics for the synergistic therapy of large solid tumors.
{"title":"Biomimetic nitric oxide nanogenerators for synergistic gas-mild photothermal therapy of large solid tumor","authors":"Caixia Tan, Ming Yan, Xinping Luo, Honghao Sun, Zhanwei Zhou, Minjie Sun","doi":"10.1016/j.apsb.2025.11.009","DOIUrl":"10.1016/j.apsb.2025.11.009","url":null,"abstract":"<div><div>The mild photothermal therapy of solid tumors was still bottlenecked by the uneven temperature distribution in tumor tissue and the autophagy-mediated resistance. Here, we leveraged the ultra-small size (approximately 0.32 nm) and autophagy inhibitory property of nitric oxide (NO) to overcome these limitations for enhanced gas-photothermal therapy of large tumors. An NO donor was loaded into mesoporous polydopamine and coated with tumor cell membranes for tumor-targeting delivery. The acid-triggered release of NO potently inhibited autophagy to block the pro-survival pathway of tumor cells. Besides, as a small-molecule gas, it diffused freely into deep regions and precisely eliminated the deep-seated tumor cells, resulting in approximately 90% tumor inhibition in the late-stage breast tumor model (>500 mm<sup>3</sup>). The NO gas therapy shows great potential for complementing other therapeutics for the synergistic therapy of large solid tumors.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 2","pages":"Pages 1074-1089"},"PeriodicalIF":14.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146176857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-27DOI: 10.1016/j.apsb.2025.11.029
Kexin Su , Junjie Qiu , Tengfei Xu , Shuai Liu
Lipid nanoparticles (LNPs) hold significant potential for mRNA-based therapeutics, as evidenced by their successful use in SARS-CoV-2 mRNA vaccines. LNPs effectively protect and transport mRNA to target sites, thereby ensuring its stability and efficient transfection. Despite the progress, some challenges remain in the development of mRNA-LNP delivery systems, such as limited targeting specificity, the complexity of formulations, and the time-consuming and high-throughput screening process. Artificial intelligence (AI) has emerged as a powerful tool to address these challenges, accelerating the design and optimization process of LNPs. AI-guided approaches can improve the efficiency of lipid structure and formulation screening by rapidly identifying key design parameters and employing predictive modeling to optimize LNP properties. The combination of AI and LNP technology offers significant advantages, including enabling the design of more personalized and precise delivery systems, streamlining the development process, and reducing the cost. This review discusses recent advancements in AI-guided mRNA-LNP delivery systems and highlights their potential to revolutionize mRNA therapeutics.
{"title":"Artificial intelligence-guided design of lipid nanoparticles for mRNA delivery","authors":"Kexin Su , Junjie Qiu , Tengfei Xu , Shuai Liu","doi":"10.1016/j.apsb.2025.11.029","DOIUrl":"10.1016/j.apsb.2025.11.029","url":null,"abstract":"<div><div>Lipid nanoparticles (LNPs) hold significant potential for mRNA-based therapeutics, as evidenced by their successful use in SARS-CoV-2 mRNA vaccines. LNPs effectively protect and transport mRNA to target sites, thereby ensuring its stability and efficient transfection. Despite the progress, some challenges remain in the development of mRNA-LNP delivery systems, such as limited targeting specificity, the complexity of formulations, and the time-consuming and high-throughput screening process. Artificial intelligence (AI) has emerged as a powerful tool to address these challenges, accelerating the design and optimization process of LNPs. AI-guided approaches can improve the efficiency of lipid structure and formulation screening by rapidly identifying key design parameters and employing predictive modeling to optimize LNP properties. The combination of AI and LNP technology offers significant advantages, including enabling the design of more personalized and precise delivery systems, streamlining the development process, and reducing the cost. This review discusses recent advancements in AI-guided mRNA-LNP delivery systems and highlights their potential to revolutionize mRNA therapeutics.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 2","pages":"Pages 709-727"},"PeriodicalIF":14.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146176839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-11DOI: 10.1016/j.apsb.2025.12.013
Simiao Wang , Jiayi Chen , Yaxin Cui , Jianming Xing , Jiayi Liu , Hao Jiang , Hongqun Yang , Huan Zhang , Man Sun , Jialin Li , Wei Liu , Zhou Chen , Wei Sun , Xiaobing Wang , Zhaogang Yang
The modulation of tumor autophagy to enhance antitumor immunity has garnered significant attention, underscoring its critical role in cancer immunotherapy. However, advanced strategies for precise autophagy-regulating drug delivery remain a pressing need. Here, we introduce a targeted small extracellular vesicles (sEVs)-based drug delivery system capable of simultaneously loading antibodies and nucleic acid drugs while ensuring their accurate release in the tumor microenvironment (TME). We developed a dual-stimulation electroporation system that integrates nanosecond electric pulses and ultrasound to enhance sEV production, yielding IL-7 mRNA-enriched sEVs that overexpress CD64 receptors for efficient capture of anti-PD-L1 antibodies. These multifunctional autophagy-inhibiting and immunomodulatory sEVs (AI-sEVs) are designed to inhibit autophagy and modulate immune responses in non-small cell lung cancer. Upon delivery to the TME, AI-sEVs mediate the enzymatic cleavage of peptide bonds, releasing IL-7 mRNA. This process induces autophagy suppression and restores MHC-I expression, which synergizes with anti-PD-L1 immune checkpoint inhibition to enhance antitumor efficacy. In conclusion, this study proposes an innovative methodology that utilizes engineered sEVs for the co-delivery of protein antibodies and genetic materials. This approach establishes a promising strategy for advancing cancer immunotherapy by targeting the modulation of autophagy.
{"title":"Multifunctional extracellular vesicles inhibiting autophagy ameliorate immunotherapy in non-small cell lung cancer","authors":"Simiao Wang , Jiayi Chen , Yaxin Cui , Jianming Xing , Jiayi Liu , Hao Jiang , Hongqun Yang , Huan Zhang , Man Sun , Jialin Li , Wei Liu , Zhou Chen , Wei Sun , Xiaobing Wang , Zhaogang Yang","doi":"10.1016/j.apsb.2025.12.013","DOIUrl":"10.1016/j.apsb.2025.12.013","url":null,"abstract":"<div><div>The modulation of tumor autophagy to enhance antitumor immunity has garnered significant attention, underscoring its critical role in cancer immunotherapy. However, advanced strategies for precise autophagy-regulating drug delivery remain a pressing need. Here, we introduce a targeted small extracellular vesicles (sEVs)-based drug delivery system capable of simultaneously loading antibodies and nucleic acid drugs while ensuring their accurate release in the tumor microenvironment (TME). We developed a dual-stimulation electroporation system that integrates nanosecond electric pulses and ultrasound to enhance sEV production, yielding <em>IL-7</em> mRNA-enriched sEVs that overexpress CD64 receptors for efficient capture of anti-PD-L1 antibodies. These multifunctional autophagy-inhibiting and immunomodulatory sEVs (AI-sEVs) are designed to inhibit autophagy and modulate immune responses in non-small cell lung cancer. Upon delivery to the TME, AI-sEVs mediate the enzymatic cleavage of peptide bonds, releasing <em>IL-7</em> mRNA. This process induces autophagy suppression and restores MHC-I expression, which synergizes with anti-PD-L1 immune checkpoint inhibition to enhance antitumor efficacy. In conclusion, this study proposes an innovative methodology that utilizes engineered sEVs for the co-delivery of protein antibodies and genetic materials. This approach establishes a promising strategy for advancing cancer immunotherapy by targeting the modulation of autophagy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 2","pages":"Pages 1022-1045"},"PeriodicalIF":14.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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