Targeted Delivery of c(RGDfk)‐Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma Therapy
Abstract Multiple myeloma (MM) is a prevalent bone marrow disorder. The challenges in managing MM include selecting chemotherapy regimens that effectively modulate the myeloma microenvironment and delivering them to the bone marrow with high efficacy and minimal toxicity. Herein, a novel bone marrow...
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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409895 |
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| author | Huiwen Liu Bo Zhang Hongrui Chen Honglan Wang Xifeng Qin Chunyan Sun Zhiqing Pang Yu Hu |
| author_facet | Huiwen Liu Bo Zhang Hongrui Chen Honglan Wang Xifeng Qin Chunyan Sun Zhiqing Pang Yu Hu |
| author_sort | Huiwen Liu |
| collection | DOAJ |
| description | Abstract Multiple myeloma (MM) is a prevalent bone marrow disorder. The challenges in managing MM include selecting chemotherapy regimens that effectively modulate the myeloma microenvironment and delivering them to the bone marrow with high efficacy and minimal toxicity. Herein, a novel bone marrow targeting strategy using c(RGDfk) peptide‐modified liposomes loaded with chemotherapeutics is developed, which can specifically recognize and hitchhike neutrophils following systemic administration, capitalizing on their natural aging process to facilitate precise drug delivery to the bone marrow, thus minimizing off‐target effects. On the one hand, c(RGDfk)‐functionalized liposomes containing carfilzomib (CRLPs) successfully transformed macrophages from M2 phenotype to M1 phenotype, enhancing immunotherapeutic responses. On the other hand, c(RGDfk)‐functionalized liposomes encapsulating BMS‐202 (BRLPs), a small molecule checkpoint inhibitor, interrupted the PD‐1/PD‐L1 axis and promoted the infiltration of cytotoxic T cells. The co‐administration of CRLPs and BRLPs successfully delivered drugs to bone marrow, leading to significant modulation of the myeloma microenvironment, reduced tumor growth, and improved survival time of MM‐bearing mouse models. These findings introduced an alternative approach to modulating the myeloma microenvironment and underscored the efficacy of hitchhiking neutrophils for bone marrow drug delivery. This strategy show advantages over traditional drug delivery methods in terms of improved efficacy and lowered toxicity. |
| format | Article |
| id | doaj-art-d7c797ffb6f6408b8b831ab437270bd2 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-d7c797ffb6f6408b8b831ab437270bd22025-08-20T01:49:41ZengWileyAdvanced Science2198-38442025-03-011212n/an/a10.1002/advs.202409895Targeted Delivery of c(RGDfk)‐Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma TherapyHuiwen Liu0Bo Zhang1Hongrui Chen2Honglan Wang3Xifeng Qin4Chunyan Sun5Zhiqing Pang6Yu Hu7Institute of Hematology Union Hospital Tongji Medical College Huazhong University of Science & Technology Wuhan Hubei 430022 ChinaInstitute of Hematology Union Hospital Tongji Medical College Huazhong University of Science & Technology Wuhan Hubei 430022 ChinaDepartment of Pathology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaInstitute of Hematology Union Hospital Tongji Medical College Huazhong University of Science & Technology Wuhan Hubei 430022 ChinaSchool of Pharmacy Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education 826 Zhangheng Road Shanghai 201203 ChinaInstitute of Hematology Union Hospital Tongji Medical College Huazhong University of Science & Technology Wuhan Hubei 430022 ChinaSchool of Pharmacy Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education 826 Zhangheng Road Shanghai 201203 ChinaInstitute of Hematology Union Hospital Tongji Medical College Huazhong University of Science & Technology Wuhan Hubei 430022 ChinaAbstract Multiple myeloma (MM) is a prevalent bone marrow disorder. The challenges in managing MM include selecting chemotherapy regimens that effectively modulate the myeloma microenvironment and delivering them to the bone marrow with high efficacy and minimal toxicity. Herein, a novel bone marrow targeting strategy using c(RGDfk) peptide‐modified liposomes loaded with chemotherapeutics is developed, which can specifically recognize and hitchhike neutrophils following systemic administration, capitalizing on their natural aging process to facilitate precise drug delivery to the bone marrow, thus minimizing off‐target effects. On the one hand, c(RGDfk)‐functionalized liposomes containing carfilzomib (CRLPs) successfully transformed macrophages from M2 phenotype to M1 phenotype, enhancing immunotherapeutic responses. On the other hand, c(RGDfk)‐functionalized liposomes encapsulating BMS‐202 (BRLPs), a small molecule checkpoint inhibitor, interrupted the PD‐1/PD‐L1 axis and promoted the infiltration of cytotoxic T cells. The co‐administration of CRLPs and BRLPs successfully delivered drugs to bone marrow, leading to significant modulation of the myeloma microenvironment, reduced tumor growth, and improved survival time of MM‐bearing mouse models. These findings introduced an alternative approach to modulating the myeloma microenvironment and underscored the efficacy of hitchhiking neutrophils for bone marrow drug delivery. This strategy show advantages over traditional drug delivery methods in terms of improved efficacy and lowered toxicity.https://doi.org/10.1002/advs.202409895bone marrow targetingc(RGDfk)liposomesmultiple myelomaneutrophil hitchhiking |
| spellingShingle | Huiwen Liu Bo Zhang Hongrui Chen Honglan Wang Xifeng Qin Chunyan Sun Zhiqing Pang Yu Hu Targeted Delivery of c(RGDfk)‐Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma Therapy Advanced Science bone marrow targeting c(RGDfk) liposomes multiple myeloma neutrophil hitchhiking |
| title | Targeted Delivery of c(RGDfk)‐Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma Therapy |
| title_full | Targeted Delivery of c(RGDfk)‐Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma Therapy |
| title_fullStr | Targeted Delivery of c(RGDfk)‐Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma Therapy |
| title_full_unstemmed | Targeted Delivery of c(RGDfk)‐Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma Therapy |
| title_short | Targeted Delivery of c(RGDfk)‐Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma Therapy |
| title_sort | targeted delivery of c rgdfk modified liposomes to bone marrow through in vivo hitchhiking neutrophils for multiple myeloma therapy |
| topic | bone marrow targeting c(RGDfk) liposomes multiple myeloma neutrophil hitchhiking |
| url | https://doi.org/10.1002/advs.202409895 |
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