{"title":"肿瘤的代谢重编程:诱导免疫抑制和纳米级药物输送系统的治疗前景。","authors":"Qianwen Li, Fansu Meng, Lina Yang, Alicia Marcelina Díaz García, Marina Parkhats, Jaiwoo Lee, Kosuke Kusamori, Makiya Nishikawa, Honghui Gu, Qi Li, Gareth R. Williams*, Zhenjiang Yang* and Yu Cai*, ","doi":"10.1021/acs.molpharmaceut.5c00342","DOIUrl":null,"url":null,"abstract":"<p >The initiation, progression, and metastasis of tumors are accompanied by metabolic reprogramming. Within the tumor immune microenvironment (TIME), the impact of metabolic alterations in tumor cells is often overlooked, leading to therapeutic failure. In reality, tumor cells and immune cells within TIME compete for nutrients, inducing hypoxia, acidosis, and other conditions that collectively foster an immunosuppressive microenvironment. Therapeutic strategies targeting metabolic reprogramming hold great promise for cancer treatment. This account systematically reviews the interplay between tumor metabolic reprogramming and the TIME, focusing on the mechanisms by which metabolic reprogramming mediates immune suppression. It highlights the strategies of nanoscale delivery systems to regulate immune cells through metabolite delivery, including diverse carrier platforms (e.g., liposomes and polymers), active targeting optimization (e.g., ligand–receptor interactions), stimuli-responsive release (e.g., pH/reactive oxygen species (ROS)-triggered systems), and multimodal synergistic therapies (e.g., phototherapy combined with metabolic inhibitors), all aimed at reshaping the metabolic balance between tumor and immune cells. Additionally, the discussion encompasses metabolic reprogramming-driven immune suppression, design strategies for nanoscale systems to reverse immunosuppression via metabolic interventions, and clinical translation. Finally, the application prospects of metabolism-targeted nanodrug delivery systems in tumor therapy are envisioned.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5193–5211"},"PeriodicalIF":4.5000,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Metabolic Reprogramming of Tumors: Induced Immunosuppression and Therapeutic Prospects of Nanoscale Drug Delivery Systems\",\"authors\":\"Qianwen Li, Fansu Meng, Lina Yang, Alicia Marcelina Díaz García, Marina Parkhats, Jaiwoo Lee, Kosuke Kusamori, Makiya Nishikawa, Honghui Gu, Qi Li, Gareth R. Williams*, Zhenjiang Yang* and Yu Cai*, \",\"doi\":\"10.1021/acs.molpharmaceut.5c00342\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >The initiation, progression, and metastasis of tumors are accompanied by metabolic reprogramming. Within the tumor immune microenvironment (TIME), the impact of metabolic alterations in tumor cells is often overlooked, leading to therapeutic failure. In reality, tumor cells and immune cells within TIME compete for nutrients, inducing hypoxia, acidosis, and other conditions that collectively foster an immunosuppressive microenvironment. Therapeutic strategies targeting metabolic reprogramming hold great promise for cancer treatment. This account systematically reviews the interplay between tumor metabolic reprogramming and the TIME, focusing on the mechanisms by which metabolic reprogramming mediates immune suppression. It highlights the strategies of nanoscale delivery systems to regulate immune cells through metabolite delivery, including diverse carrier platforms (e.g., liposomes and polymers), active targeting optimization (e.g., ligand–receptor interactions), stimuli-responsive release (e.g., pH/reactive oxygen species (ROS)-triggered systems), and multimodal synergistic therapies (e.g., phototherapy combined with metabolic inhibitors), all aimed at reshaping the metabolic balance between tumor and immune cells. Additionally, the discussion encompasses metabolic reprogramming-driven immune suppression, design strategies for nanoscale systems to reverse immunosuppression via metabolic interventions, and clinical translation. Finally, the application prospects of metabolism-targeted nanodrug delivery systems in tumor therapy are envisioned.</p>\",\"PeriodicalId\":52,\"journal\":{\"name\":\"Molecular Pharmaceutics\",\"volume\":\"22 9\",\"pages\":\"5193–5211\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Pharmaceutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.5c00342\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.5c00342","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Metabolic Reprogramming of Tumors: Induced Immunosuppression and Therapeutic Prospects of Nanoscale Drug Delivery Systems
The initiation, progression, and metastasis of tumors are accompanied by metabolic reprogramming. Within the tumor immune microenvironment (TIME), the impact of metabolic alterations in tumor cells is often overlooked, leading to therapeutic failure. In reality, tumor cells and immune cells within TIME compete for nutrients, inducing hypoxia, acidosis, and other conditions that collectively foster an immunosuppressive microenvironment. Therapeutic strategies targeting metabolic reprogramming hold great promise for cancer treatment. This account systematically reviews the interplay between tumor metabolic reprogramming and the TIME, focusing on the mechanisms by which metabolic reprogramming mediates immune suppression. It highlights the strategies of nanoscale delivery systems to regulate immune cells through metabolite delivery, including diverse carrier platforms (e.g., liposomes and polymers), active targeting optimization (e.g., ligand–receptor interactions), stimuli-responsive release (e.g., pH/reactive oxygen species (ROS)-triggered systems), and multimodal synergistic therapies (e.g., phototherapy combined with metabolic inhibitors), all aimed at reshaping the metabolic balance between tumor and immune cells. Additionally, the discussion encompasses metabolic reprogramming-driven immune suppression, design strategies for nanoscale systems to reverse immunosuppression via metabolic interventions, and clinical translation. Finally, the application prospects of metabolism-targeted nanodrug delivery systems in tumor therapy are envisioned.
期刊介绍:
Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development.
Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.