Sequentially Activated Smart DNA Nanospheres for Photoimmunotherapy and Immune Checkpoint Blockade

Abstract Due to the inherent immunosuppression and immune evasion of cancer cells, combining photoimmunotherapy with immune checkpoint blockade leverages phototherapy and immune enhancement, overcoming mutual limitations and demonstrating significant anticancer potential. The main challenges include...

Full description

Saved in:
Bibliographic Details
Main Authors: Yu Chen, Yu Guo, Wen Cheng, Jiahao Fan, Jiacheng Li, Jiajia Song, Xiaohai Yang, Kemin Wang, Jin Huang
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202410632
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832593572240556032
author Yu Chen
Yu Guo
Wen Cheng
Jiahao Fan
Jiacheng Li
Jiajia Song
Xiaohai Yang
Kemin Wang
Jin Huang
author_facet Yu Chen
Yu Guo
Wen Cheng
Jiahao Fan
Jiacheng Li
Jiajia Song
Xiaohai Yang
Kemin Wang
Jin Huang
author_sort Yu Chen
collection DOAJ
description Abstract Due to the inherent immunosuppression and immune evasion of cancer cells, combining photoimmunotherapy with immune checkpoint blockade leverages phototherapy and immune enhancement, overcoming mutual limitations and demonstrating significant anticancer potential. The main challenges include nonspecific accumulation of agents, uncontrolled activation, and drug carrier safety. Smart DNA nanospheres (NS) is developed with targeted delivery and controllable release of photosensitizers and immune agents to achieve effective synergistic therapy and minimize side effects. The multifunctional NS incorporate a targeting module for programming aptamers, a response module for programming i‐motif and DNA/RNA hybrid sequences, and a therapeutic module for packaging photosensitizers and PD‐L1 siRNA. NS navigate to the tumor site and are sequentially activated by intracellular acid and enzymes to release photosensitizers and programmed death ligand 1 (PD‐L1) small interfering RNA (siRNA)a. Besides tumor killing and immune promotion, activated NS downregulate PD‐L1 expression, alleviating immune tolerance and evasion, thus enhancing the immune response. These results indicate that NS significantly enhance antitumor immune responses, synergistically improve antitumor efficacy, and reduce systemic toxicity. This study broadens the application of DNA nanomaterials in precision drug delivery and tumor therapy.
format Article
id doaj-art-cdf1159516a544be8ad19cbd75ddc0e8
institution Kabale University
issn 2198-3844
language English
publishDate 2025-01-01
publisher Wiley
record_format Article
series Advanced Science
spelling doaj-art-cdf1159516a544be8ad19cbd75ddc0e82025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202410632Sequentially Activated Smart DNA Nanospheres for Photoimmunotherapy and Immune Checkpoint BlockadeYu Chen0Yu Guo1Wen Cheng2Jiahao Fan3Jiacheng Li4Jiajia Song5Xiaohai Yang6Kemin Wang7Jin Huang8State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Key Laboratory for Bio‐Nanotechnology and Molecular Engineering of Hunan Province Hunan University Changsha 410082 P. R. ChinaState Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Key Laboratory for Bio‐Nanotechnology and Molecular Engineering of Hunan Province Hunan University Changsha 410082 P. R. ChinaState Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Key Laboratory for Bio‐Nanotechnology and Molecular Engineering of Hunan Province Hunan University Changsha 410082 P. R. ChinaState Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Key Laboratory for Bio‐Nanotechnology and Molecular Engineering of Hunan Province Hunan University Changsha 410082 P. R. ChinaState Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Key Laboratory for Bio‐Nanotechnology and Molecular Engineering of Hunan Province Hunan University Changsha 410082 P. R. ChinaState Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Key Laboratory for Bio‐Nanotechnology and Molecular Engineering of Hunan Province Hunan University Changsha 410082 P. R. ChinaState Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Key Laboratory for Bio‐Nanotechnology and Molecular Engineering of Hunan Province Hunan University Changsha 410082 P. R. ChinaState Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Key Laboratory for Bio‐Nanotechnology and Molecular Engineering of Hunan Province Hunan University Changsha 410082 P. R. ChinaState Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Key Laboratory for Bio‐Nanotechnology and Molecular Engineering of Hunan Province Hunan University Changsha 410082 P. R. ChinaAbstract Due to the inherent immunosuppression and immune evasion of cancer cells, combining photoimmunotherapy with immune checkpoint blockade leverages phototherapy and immune enhancement, overcoming mutual limitations and demonstrating significant anticancer potential. The main challenges include nonspecific accumulation of agents, uncontrolled activation, and drug carrier safety. Smart DNA nanospheres (NS) is developed with targeted delivery and controllable release of photosensitizers and immune agents to achieve effective synergistic therapy and minimize side effects. The multifunctional NS incorporate a targeting module for programming aptamers, a response module for programming i‐motif and DNA/RNA hybrid sequences, and a therapeutic module for packaging photosensitizers and PD‐L1 siRNA. NS navigate to the tumor site and are sequentially activated by intracellular acid and enzymes to release photosensitizers and programmed death ligand 1 (PD‐L1) small interfering RNA (siRNA)a. Besides tumor killing and immune promotion, activated NS downregulate PD‐L1 expression, alleviating immune tolerance and evasion, thus enhancing the immune response. These results indicate that NS significantly enhance antitumor immune responses, synergistically improve antitumor efficacy, and reduce systemic toxicity. This study broadens the application of DNA nanomaterials in precision drug delivery and tumor therapy.https://doi.org/10.1002/advs.202410632DNA nanospheresdrug deliveryimmune checkpoint blockadephotoimmunotherapytumor therapy
spellingShingle Yu Chen
Yu Guo
Wen Cheng
Jiahao Fan
Jiacheng Li
Jiajia Song
Xiaohai Yang
Kemin Wang
Jin Huang
Sequentially Activated Smart DNA Nanospheres for Photoimmunotherapy and Immune Checkpoint Blockade
Advanced Science
DNA nanospheres
drug delivery
immune checkpoint blockade
photoimmunotherapy
tumor therapy
title Sequentially Activated Smart DNA Nanospheres for Photoimmunotherapy and Immune Checkpoint Blockade
title_full Sequentially Activated Smart DNA Nanospheres for Photoimmunotherapy and Immune Checkpoint Blockade
title_fullStr Sequentially Activated Smart DNA Nanospheres for Photoimmunotherapy and Immune Checkpoint Blockade
title_full_unstemmed Sequentially Activated Smart DNA Nanospheres for Photoimmunotherapy and Immune Checkpoint Blockade
title_short Sequentially Activated Smart DNA Nanospheres for Photoimmunotherapy and Immune Checkpoint Blockade
title_sort sequentially activated smart dna nanospheres for photoimmunotherapy and immune checkpoint blockade
topic DNA nanospheres
drug delivery
immune checkpoint blockade
photoimmunotherapy
tumor therapy
url https://doi.org/10.1002/advs.202410632
work_keys_str_mv AT yuchen sequentiallyactivatedsmartdnananospheresforphotoimmunotherapyandimmunecheckpointblockade
AT yuguo sequentiallyactivatedsmartdnananospheresforphotoimmunotherapyandimmunecheckpointblockade
AT wencheng sequentiallyactivatedsmartdnananospheresforphotoimmunotherapyandimmunecheckpointblockade
AT jiahaofan sequentiallyactivatedsmartdnananospheresforphotoimmunotherapyandimmunecheckpointblockade
AT jiachengli sequentiallyactivatedsmartdnananospheresforphotoimmunotherapyandimmunecheckpointblockade
AT jiajiasong sequentiallyactivatedsmartdnananospheresforphotoimmunotherapyandimmunecheckpointblockade
AT xiaohaiyang sequentiallyactivatedsmartdnananospheresforphotoimmunotherapyandimmunecheckpointblockade
AT keminwang sequentiallyactivatedsmartdnananospheresforphotoimmunotherapyandimmunecheckpointblockade
AT jinhuang sequentiallyactivatedsmartdnananospheresforphotoimmunotherapyandimmunecheckpointblockade