Biomimetic Targeted Co‐Delivery System Engineered from Genomic Insights for Precision Treatment of Osteosarcoma
Abstract The high heterogeneity and severe side effects of chemotherapy are major factors contributing to the failure of osteosarcoma treatment. Herein, a comprehensive genomic analysis is conducted, and identified two prominent characteristics of osteosarcoma: significant cyclin‐dependent kinases 4...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202410427 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841543126919938048 |
|---|---|
| author | Tianqi Luo Zhijin Fan Anyu Zeng Anqi Wang Yuanwei Pan Yanyang Xu Hongmin Chen Weiqing Chen Dingmeng Nie Jiaming Lin Anfei Huang Ming Gong Yufeng Huang Yun Ding Xiaojun Zhu Lang Rao Jin Wang |
| author_facet | Tianqi Luo Zhijin Fan Anyu Zeng Anqi Wang Yuanwei Pan Yanyang Xu Hongmin Chen Weiqing Chen Dingmeng Nie Jiaming Lin Anfei Huang Ming Gong Yufeng Huang Yun Ding Xiaojun Zhu Lang Rao Jin Wang |
| author_sort | Tianqi Luo |
| collection | DOAJ |
| description | Abstract The high heterogeneity and severe side effects of chemotherapy are major factors contributing to the failure of osteosarcoma treatment. Herein, a comprehensive genomic analysis is conducted, and identified two prominent characteristics of osteosarcoma: significant cyclin‐dependent kinases 4 (CDK4) amplification and homologous recombination repair deficiency. Based on these findings, a co‐delivery system loaded with CDK4/6 inhibitors and poly ADP‐ribose polymerase (PARP) inhibitors is designed. By employing metal–organic frameworks (MOFs) as carriers, issue of drug insolubility is effectively addressed, while also enabling controlled release in response to the tumor microenvironment. To enhance targeting capability and biocompatibility, the MOFs are further coated with a bio‐membrane targeting B7H3. This targeted biomimetic co‐delivery system possesses several key features: 1) it can precisely target osteosarcoma with high B7H3 expression; 2) the combination of CDK4/6 inhibitors and PARP inhibitors exhibits synergistic effects, significantly impairing tumor's DNA repair capacity; and 3) the system has the potential for combination with photodynamic therapy, amplifying DNA repair defects to maximize tumor cell eradication. Furthermore, it is observed that this co‐delivery system can activate immune microenvironment, increasing CD8+ T cell infiltration and converting osteosarcoma from an immune‐cold to an immune‐hot tumor. In summary, the co‐delivery system is an effective therapeutic strategy and holds promise as a novel approach for osteosarcoma treatment. |
| format | Article |
| id | doaj-art-11e62a0764304828a4034b2644239853 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-11e62a0764304828a4034b26442398532025-01-13T15:29:43ZengWileyAdvanced Science2198-38442025-01-01122n/an/a10.1002/advs.202410427Biomimetic Targeted Co‐Delivery System Engineered from Genomic Insights for Precision Treatment of OsteosarcomaTianqi Luo0Zhijin Fan1Anyu Zeng2Anqi Wang3Yuanwei Pan4Yanyang Xu5Hongmin Chen6Weiqing Chen7Dingmeng Nie8Jiaming Lin9Anfei Huang10Ming Gong11Yufeng Huang12Yun Ding13Xiaojun Zhu14Lang Rao15Jin Wang16Department of Musculoskeletal Oncology State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaInstitute for Engineering Medicine Kunming Medical University Kunming 650500 ChinaDepartment of Musculoskeletal Oncology State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaDepartment of Musculoskeletal Oncology State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaInstitute of Chemical Biology Shenzhen Bay Laboratory Shenzhen 518132 ChinaDepartment of Joint Surgery Guangzhou First People's Hospital School of Medicine South China University of Technology Guangzhou 510060 ChinaDepartment of Musculoskeletal Oncology State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaDepartment of Musculoskeletal Oncology State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaInstitute of Chemical Biology Shenzhen Bay Laboratory Shenzhen 518132 ChinaDepartment of Musculoskeletal Oncology State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaDepartment of Musculoskeletal Oncology State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaDepartment of Pediatric Orthopaedics Guangzhou Women and Children's Medical Center Guangdong Provincial Clinical Research Center for Child Health Guangzhou Medical University Guangzhou 510630 ChinaDepartment of Musculoskeletal Oncology State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaDepartment of Breast Oncology State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaDepartment of Musculoskeletal Oncology State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaInstitute of Chemical Biology Shenzhen Bay Laboratory Shenzhen 518132 ChinaDepartment of Musculoskeletal Oncology State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaAbstract The high heterogeneity and severe side effects of chemotherapy are major factors contributing to the failure of osteosarcoma treatment. Herein, a comprehensive genomic analysis is conducted, and identified two prominent characteristics of osteosarcoma: significant cyclin‐dependent kinases 4 (CDK4) amplification and homologous recombination repair deficiency. Based on these findings, a co‐delivery system loaded with CDK4/6 inhibitors and poly ADP‐ribose polymerase (PARP) inhibitors is designed. By employing metal–organic frameworks (MOFs) as carriers, issue of drug insolubility is effectively addressed, while also enabling controlled release in response to the tumor microenvironment. To enhance targeting capability and biocompatibility, the MOFs are further coated with a bio‐membrane targeting B7H3. This targeted biomimetic co‐delivery system possesses several key features: 1) it can precisely target osteosarcoma with high B7H3 expression; 2) the combination of CDK4/6 inhibitors and PARP inhibitors exhibits synergistic effects, significantly impairing tumor's DNA repair capacity; and 3) the system has the potential for combination with photodynamic therapy, amplifying DNA repair defects to maximize tumor cell eradication. Furthermore, it is observed that this co‐delivery system can activate immune microenvironment, increasing CD8+ T cell infiltration and converting osteosarcoma from an immune‐cold to an immune‐hot tumor. In summary, the co‐delivery system is an effective therapeutic strategy and holds promise as a novel approach for osteosarcoma treatment.https://doi.org/10.1002/advs.202410427B7H3bioinformaticsHomologous recombination repairnanoparticlesosteosarcoma |
| spellingShingle | Tianqi Luo Zhijin Fan Anyu Zeng Anqi Wang Yuanwei Pan Yanyang Xu Hongmin Chen Weiqing Chen Dingmeng Nie Jiaming Lin Anfei Huang Ming Gong Yufeng Huang Yun Ding Xiaojun Zhu Lang Rao Jin Wang Biomimetic Targeted Co‐Delivery System Engineered from Genomic Insights for Precision Treatment of Osteosarcoma Advanced Science B7H3 bioinformatics Homologous recombination repair nanoparticles osteosarcoma |
| title | Biomimetic Targeted Co‐Delivery System Engineered from Genomic Insights for Precision Treatment of Osteosarcoma |
| title_full | Biomimetic Targeted Co‐Delivery System Engineered from Genomic Insights for Precision Treatment of Osteosarcoma |
| title_fullStr | Biomimetic Targeted Co‐Delivery System Engineered from Genomic Insights for Precision Treatment of Osteosarcoma |
| title_full_unstemmed | Biomimetic Targeted Co‐Delivery System Engineered from Genomic Insights for Precision Treatment of Osteosarcoma |
| title_short | Biomimetic Targeted Co‐Delivery System Engineered from Genomic Insights for Precision Treatment of Osteosarcoma |
| title_sort | biomimetic targeted co delivery system engineered from genomic insights for precision treatment of osteosarcoma |
| topic | B7H3 bioinformatics Homologous recombination repair nanoparticles osteosarcoma |
| url | https://doi.org/10.1002/advs.202410427 |
| work_keys_str_mv | AT tianqiluo biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT zhijinfan biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT anyuzeng biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT anqiwang biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT yuanweipan biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT yanyangxu biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT hongminchen biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT weiqingchen biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT dingmengnie biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT jiaminglin biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT anfeihuang biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT minggong biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT yufenghuang biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT yunding biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT xiaojunzhu biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT langrao biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma AT jinwang biomimetictargetedcodeliverysystemengineeredfromgenomicinsightsforprecisiontreatmentofosteosarcoma |