A Spatially Distributed Microneedle System for Bioorthogonal T Cell‐Guided Cancer Therapy
Abstract Chimeric antigen receptor (CAR)‐T cell therapy represents a promising strategy for cancer treatment. However, the diversity of solid tumor antigens and the poor infiltration of CAR‐T cells significantly hinder the efficacy of CAR‐T therapies against tumors. Here, a spatially distributed mic...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-04-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202416841 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849767186984337408 |
|---|---|
| author | Lanya Li Fei Wang Shushan Mo Junyao Deng Xueyi Wang Jiacong Ai Yingxian Xiao Yan Zeng Qishan Li Yixin Zhang Limin Cai Zhenhua Li |
| author_facet | Lanya Li Fei Wang Shushan Mo Junyao Deng Xueyi Wang Jiacong Ai Yingxian Xiao Yan Zeng Qishan Li Yixin Zhang Limin Cai Zhenhua Li |
| author_sort | Lanya Li |
| collection | DOAJ |
| description | Abstract Chimeric antigen receptor (CAR)‐T cell therapy represents a promising strategy for cancer treatment. However, the diversity of solid tumor antigens and the poor infiltration of CAR‐T cells significantly hinder the efficacy of CAR‐T therapies against tumors. Here, a spatially distributed microneedle system (SDMNS) is developed that leverages bioorthogonal reactions to activate and guide endogenous T cells to tumors for effective destruction. The SDMNS consists of two dissolving microneedles, each loaded with complementary bioorthogonal groups and applied separately to lymph nodes and tumor sites. One microneedle loaded with two dibenzocyclooctyne (DBCO)‐modified antibodies activates T cells and labels them with bioorthogonal groups in lymph nodes. The other microneedle, containing N‐azidoacetylmannosamine‐tetraacylated (Ac4ManNAz) for glycometabolic labeling of tumor cells, and the T cell chemotactic factor IP10, is applied directly to the tumor site. The in vivo studies demonstrate that SDMNS effectively directs the migration and infiltration of endogenous activated T cells into the tumors. Through a bioorthogonal click reaction, DBCO‐modified T cells conjugate with azide (N3)‐modified tumor cells, eliciting robust antitumor immune responses and durable immune memory. The SDMNS offers a novel strategy to overcomes tumor heterogeneity by facilitating the directed migration of endogenous T cells. |
| format | Article |
| id | doaj-art-122c91b9b8f4482c868d0844e86101f0 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-122c91b9b8f4482c868d0844e86101f02025-08-20T03:04:17ZengWileyAdvanced Science2198-38442025-04-011213n/an/a10.1002/advs.202416841A Spatially Distributed Microneedle System for Bioorthogonal T Cell‐Guided Cancer TherapyLanya Li0Fei Wang1Shushan Mo2Junyao Deng3Xueyi Wang4Jiacong Ai5Yingxian Xiao6Yan Zeng7Qishan Li8Yixin Zhang9Limin Cai10Zhenhua Li11The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) Dongguan 523059 ChinaThe Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) Dongguan 523059 ChinaCollege of Pharmaceutical Science Key Laboratory of Pharmaceutical Quality Control of Hebei Province Hebei University Baoding 071002 ChinaThe Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) Dongguan 523059 ChinaThe Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) Dongguan 523059 ChinaThe Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) Dongguan 523059 ChinaThe Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) Dongguan 523059 ChinaThe Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) Dongguan 523059 ChinaThe Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) Dongguan 523059 ChinaThe Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) Dongguan 523059 ChinaThe Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) Dongguan 523059 ChinaThe Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) Dongguan 523059 ChinaAbstract Chimeric antigen receptor (CAR)‐T cell therapy represents a promising strategy for cancer treatment. However, the diversity of solid tumor antigens and the poor infiltration of CAR‐T cells significantly hinder the efficacy of CAR‐T therapies against tumors. Here, a spatially distributed microneedle system (SDMNS) is developed that leverages bioorthogonal reactions to activate and guide endogenous T cells to tumors for effective destruction. The SDMNS consists of two dissolving microneedles, each loaded with complementary bioorthogonal groups and applied separately to lymph nodes and tumor sites. One microneedle loaded with two dibenzocyclooctyne (DBCO)‐modified antibodies activates T cells and labels them with bioorthogonal groups in lymph nodes. The other microneedle, containing N‐azidoacetylmannosamine‐tetraacylated (Ac4ManNAz) for glycometabolic labeling of tumor cells, and the T cell chemotactic factor IP10, is applied directly to the tumor site. The in vivo studies demonstrate that SDMNS effectively directs the migration and infiltration of endogenous activated T cells into the tumors. Through a bioorthogonal click reaction, DBCO‐modified T cells conjugate with azide (N3)‐modified tumor cells, eliciting robust antitumor immune responses and durable immune memory. The SDMNS offers a novel strategy to overcomes tumor heterogeneity by facilitating the directed migration of endogenous T cells.https://doi.org/10.1002/advs.202416841bioorthogonal reactionlymph nodesolid tumorsspatially distributed microneedleT cell migration |
| spellingShingle | Lanya Li Fei Wang Shushan Mo Junyao Deng Xueyi Wang Jiacong Ai Yingxian Xiao Yan Zeng Qishan Li Yixin Zhang Limin Cai Zhenhua Li A Spatially Distributed Microneedle System for Bioorthogonal T Cell‐Guided Cancer Therapy Advanced Science bioorthogonal reaction lymph node solid tumors spatially distributed microneedle T cell migration |
| title | A Spatially Distributed Microneedle System for Bioorthogonal T Cell‐Guided Cancer Therapy |
| title_full | A Spatially Distributed Microneedle System for Bioorthogonal T Cell‐Guided Cancer Therapy |
| title_fullStr | A Spatially Distributed Microneedle System for Bioorthogonal T Cell‐Guided Cancer Therapy |
| title_full_unstemmed | A Spatially Distributed Microneedle System for Bioorthogonal T Cell‐Guided Cancer Therapy |
| title_short | A Spatially Distributed Microneedle System for Bioorthogonal T Cell‐Guided Cancer Therapy |
| title_sort | spatially distributed microneedle system for bioorthogonal t cell guided cancer therapy |
| topic | bioorthogonal reaction lymph node solid tumors spatially distributed microneedle T cell migration |
| url | https://doi.org/10.1002/advs.202416841 |
| work_keys_str_mv | AT lanyali aspatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT feiwang aspatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT shushanmo aspatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT junyaodeng aspatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT xueyiwang aspatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT jiacongai aspatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT yingxianxiao aspatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT yanzeng aspatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT qishanli aspatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT yixinzhang aspatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT limincai aspatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT zhenhuali aspatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT lanyali spatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT feiwang spatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT shushanmo spatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT junyaodeng spatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT xueyiwang spatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT jiacongai spatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT yingxianxiao spatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT yanzeng spatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT qishanli spatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT yixinzhang spatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT limincai spatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy AT zhenhuali spatiallydistributedmicroneedlesystemforbioorthogonaltcellguidedcancertherapy |