Ultrasound-activated prodrug-loaded liposome for efficient cancer targeting therapy without chemotherapy-induced side effects
Abstract Background Off-targeted distribution of chemotherapeutic drugs causes severe side effects, further leading to poor prognosis and patient compliance. Ligand/receptor-mediated targeted drug delivery can improve drug accumulation in the tumor but it always attenuated by protein corona barriers...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-01-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-02195-5 |
| _version_ | 1797362898264129536 |
|---|---|
| author | Yifan Jiang Hongjian Chen Tao Lin Chao Zhang Jiaxin Shen Jifan Chen Yanan Zhao Wen Xu Guowei Wang Pintong Huang |
| author_facet | Yifan Jiang Hongjian Chen Tao Lin Chao Zhang Jiaxin Shen Jifan Chen Yanan Zhao Wen Xu Guowei Wang Pintong Huang |
| author_sort | Yifan Jiang |
| collection | DOAJ |
| description | Abstract Background Off-targeted distribution of chemotherapeutic drugs causes severe side effects, further leading to poor prognosis and patient compliance. Ligand/receptor-mediated targeted drug delivery can improve drug accumulation in the tumor but it always attenuated by protein corona barriers. Results To address these problems, a radically different strategy is proposed that can leave the off-targeted drugs inactive but activate the tumor-distributed drugs for cancer-targeting therapy in a tumor microenvironment-independent manner. The feasibility and effectiveness of this strategy is demonstrated by developing an ultrasound (US)-activated prodrug-loaded liposome (CPBSN38L) comprising the sonosensitizer chlorin e6 (Ce6)-modified lipids and the prodrug of pinacol boronic ester-conjugated SN38 (PBSN38). Once CPBSN38L is accumulated in the tumor and internalized into the cancer cells, under US irradiation, the sonosensitizer Ce6 rapidly induces extensive production of intracellular reactive oxygen species (ROS), thereby initiating a cascade amplified ROS-responsive activation of PBSN38 to release the active SN38 for inducing cell apoptosis. If some of the injected CPBSN38L is distributed into normal tissues, the inactive PBSN38 exerts no pharmacological activity on normal cells. CPBSN38L exhibited strong anticancer activity in multiple murine tumor models of colon adenocarcinoma and hepatocellular carcinoma with no chemotherapy-induced side effects, compared with the standard first-line anticancer drugs irinotecan and topotecan. Conclusions This study established a side-effect-evitable, universal, and feasible strategy for cancer-targeting therapy. Graphical Abstract |
| first_indexed | 2024-03-08T16:14:01Z |
| format | Article |
| id | doaj.art-1ec9d0931be941e6986be916a35f3e6a |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-08T16:14:01Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-1ec9d0931be941e6986be916a35f3e6a2024-01-07T12:43:13ZengBMCJournal of Nanobiotechnology1477-31552024-01-0122111210.1186/s12951-023-02195-5Ultrasound-activated prodrug-loaded liposome for efficient cancer targeting therapy without chemotherapy-induced side effectsYifan Jiang0Hongjian Chen1Tao Lin2Chao Zhang3Jiaxin Shen4Jifan Chen5Yanan Zhao6Wen Xu7Guowei Wang8Pintong Huang9Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang UniversityDepartment of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang UniversityDepartment of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang UniversityDepartment of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang UniversityDepartment of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang UniversityDepartment of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang UniversityDepartment of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang UniversityDepartment of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang UniversityDepartment of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang UniversityDepartment of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang UniversityAbstract Background Off-targeted distribution of chemotherapeutic drugs causes severe side effects, further leading to poor prognosis and patient compliance. Ligand/receptor-mediated targeted drug delivery can improve drug accumulation in the tumor but it always attenuated by protein corona barriers. Results To address these problems, a radically different strategy is proposed that can leave the off-targeted drugs inactive but activate the tumor-distributed drugs for cancer-targeting therapy in a tumor microenvironment-independent manner. The feasibility and effectiveness of this strategy is demonstrated by developing an ultrasound (US)-activated prodrug-loaded liposome (CPBSN38L) comprising the sonosensitizer chlorin e6 (Ce6)-modified lipids and the prodrug of pinacol boronic ester-conjugated SN38 (PBSN38). Once CPBSN38L is accumulated in the tumor and internalized into the cancer cells, under US irradiation, the sonosensitizer Ce6 rapidly induces extensive production of intracellular reactive oxygen species (ROS), thereby initiating a cascade amplified ROS-responsive activation of PBSN38 to release the active SN38 for inducing cell apoptosis. If some of the injected CPBSN38L is distributed into normal tissues, the inactive PBSN38 exerts no pharmacological activity on normal cells. CPBSN38L exhibited strong anticancer activity in multiple murine tumor models of colon adenocarcinoma and hepatocellular carcinoma with no chemotherapy-induced side effects, compared with the standard first-line anticancer drugs irinotecan and topotecan. Conclusions This study established a side-effect-evitable, universal, and feasible strategy for cancer-targeting therapy. Graphical Abstracthttps://doi.org/10.1186/s12951-023-02195-5UltrasoundLiposomeProdrugStimuli-responsive drug deliveryCancer targeting therapy |
| spellingShingle | Yifan Jiang Hongjian Chen Tao Lin Chao Zhang Jiaxin Shen Jifan Chen Yanan Zhao Wen Xu Guowei Wang Pintong Huang Ultrasound-activated prodrug-loaded liposome for efficient cancer targeting therapy without chemotherapy-induced side effects Journal of Nanobiotechnology Ultrasound Liposome Prodrug Stimuli-responsive drug delivery Cancer targeting therapy |
| title | Ultrasound-activated prodrug-loaded liposome for efficient cancer targeting therapy without chemotherapy-induced side effects |
| title_full | Ultrasound-activated prodrug-loaded liposome for efficient cancer targeting therapy without chemotherapy-induced side effects |
| title_fullStr | Ultrasound-activated prodrug-loaded liposome for efficient cancer targeting therapy without chemotherapy-induced side effects |
| title_full_unstemmed | Ultrasound-activated prodrug-loaded liposome for efficient cancer targeting therapy without chemotherapy-induced side effects |
| title_short | Ultrasound-activated prodrug-loaded liposome for efficient cancer targeting therapy without chemotherapy-induced side effects |
| title_sort | ultrasound activated prodrug loaded liposome for efficient cancer targeting therapy without chemotherapy induced side effects |
| topic | Ultrasound Liposome Prodrug Stimuli-responsive drug delivery Cancer targeting therapy |
| url | https://doi.org/10.1186/s12951-023-02195-5 |
| work_keys_str_mv | AT yifanjiang ultrasoundactivatedprodrugloadedliposomeforefficientcancertargetingtherapywithoutchemotherapyinducedsideeffects AT hongjianchen ultrasoundactivatedprodrugloadedliposomeforefficientcancertargetingtherapywithoutchemotherapyinducedsideeffects AT taolin ultrasoundactivatedprodrugloadedliposomeforefficientcancertargetingtherapywithoutchemotherapyinducedsideeffects AT chaozhang ultrasoundactivatedprodrugloadedliposomeforefficientcancertargetingtherapywithoutchemotherapyinducedsideeffects AT jiaxinshen ultrasoundactivatedprodrugloadedliposomeforefficientcancertargetingtherapywithoutchemotherapyinducedsideeffects AT jifanchen ultrasoundactivatedprodrugloadedliposomeforefficientcancertargetingtherapywithoutchemotherapyinducedsideeffects AT yananzhao ultrasoundactivatedprodrugloadedliposomeforefficientcancertargetingtherapywithoutchemotherapyinducedsideeffects AT wenxu ultrasoundactivatedprodrugloadedliposomeforefficientcancertargetingtherapywithoutchemotherapyinducedsideeffects AT guoweiwang ultrasoundactivatedprodrugloadedliposomeforefficientcancertargetingtherapywithoutchemotherapyinducedsideeffects AT pintonghuang ultrasoundactivatedprodrugloadedliposomeforefficientcancertargetingtherapywithoutchemotherapyinducedsideeffects |