Novel nanotherapeutics for cancer immunotherapy by albumin nanoparticles functionalized with PD-1 and PD-L1 aptamers
Abstract Background PD-1/PD-L1 blockade plays a crucial role in cancer immunotherapy. Exploration of new technologies to further enhance the efficacy of PD-1/PD-L1 blockade is therefore of potential medical importance. Nanotherapeutics can accumulate in tumor tissues due to enhanced permeability and...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Cancer Nanotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12645-023-00239-x |
| _version_ | 1797363638489579520 |
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| author | Qiping Jiang Fengjiao Yao Yacong An Xialian Lai Xundou Li Zhen Yu Xian-Da Yang |
| author_facet | Qiping Jiang Fengjiao Yao Yacong An Xialian Lai Xundou Li Zhen Yu Xian-Da Yang |
| author_sort | Qiping Jiang |
| collection | DOAJ |
| description | Abstract Background PD-1/PD-L1 blockade plays a crucial role in cancer immunotherapy. Exploration of new technologies to further enhance the efficacy of PD-1/PD-L1 blockade is therefore of potential medical importance. Nanotherapeutics can accumulate in tumor tissues due to enhanced permeability and retention (EPR) effects. In this study, a novel nanotherapeutic for cancer immunotherapy was implemented with albumin nanoparticles functionalized by both PD-1 and PD-L1 aptamers. Results Albumin nanoparticles (NP) were functionalized with either PD-1 aptamers (PD1-NP), PD-L1 aptamers (PDL1-NP), or both types of aptamers (PD1-NP-PDL1). Average sizes of PD1-NP, PDL1-NP, and PD1-NP-PDL1 were 141.8 nm, 141.8 nm, and 164.2 nm, respectively. PD1-NP had good affinity for activated T cells that expresses PD-1. Similarly, PDL1-NP could bind with MDA-MB-231 or CT26 tumor cells that express PD-L1. Moreover, the bispecific PD1-NP-PDL1 could bind with both the activated T cells and the PD-L1-expressing tumor cells, and tether the two type of cells together. Functionally, aptamer-modified nanoparticles exhibited stronger immune-stimulating effects vs. free aptamers. Specifically, PD1-NP or PDL1-NP induced stronger lymphocyte-mediated cytotoxicity against PD-L1-expressing tumor cells in vitro vs. free PD-1 or PD-L1 aptamers. Animal studies also showed that PD1-NP or PDL1-NP significantly improved antitumor efficacy against CT26 colon cancer in vivo vs. free PD-1 or PD-L1 aptamers. Importantly, the bispecific PD1-NP-PDL1 further boosted the in vivo antitumor efficacy compared with PD1-NP or PDL1-NP, without raising systemic toxicity. Conclusion The results suggest that the bispecific PD1-NP-PDL1 is a promising nanotherapeutic to improve the efficacy of PD-1/PD-L1 blockade, and may have application potential in colon cancer treatment. |
| first_indexed | 2024-03-08T16:22:58Z |
| format | Article |
| id | doaj.art-0d11a9e3e7a34e57b34d208719254805 |
| institution | Directory Open Access Journal |
| issn | 1868-6958 1868-6966 |
| language | English |
| last_indexed | 2024-03-08T16:22:58Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Nanotechnology |
| spelling | doaj.art-0d11a9e3e7a34e57b34d2087192548052024-01-07T12:11:14ZengBMCCancer Nanotechnology1868-69581868-69662024-01-0115111610.1186/s12645-023-00239-xNovel nanotherapeutics for cancer immunotherapy by albumin nanoparticles functionalized with PD-1 and PD-L1 aptamersQiping Jiang0Fengjiao Yao1Yacong An2Xialian Lai3Xundou Li4Zhen Yu5Xian-Da Yang6Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegePeking University First HospitalInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeDepartment of Clinical Laboratory, Third Central Hospital of Tianjin Affiliated to Nankai UniversityInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeAbstract Background PD-1/PD-L1 blockade plays a crucial role in cancer immunotherapy. Exploration of new technologies to further enhance the efficacy of PD-1/PD-L1 blockade is therefore of potential medical importance. Nanotherapeutics can accumulate in tumor tissues due to enhanced permeability and retention (EPR) effects. In this study, a novel nanotherapeutic for cancer immunotherapy was implemented with albumin nanoparticles functionalized by both PD-1 and PD-L1 aptamers. Results Albumin nanoparticles (NP) were functionalized with either PD-1 aptamers (PD1-NP), PD-L1 aptamers (PDL1-NP), or both types of aptamers (PD1-NP-PDL1). Average sizes of PD1-NP, PDL1-NP, and PD1-NP-PDL1 were 141.8 nm, 141.8 nm, and 164.2 nm, respectively. PD1-NP had good affinity for activated T cells that expresses PD-1. Similarly, PDL1-NP could bind with MDA-MB-231 or CT26 tumor cells that express PD-L1. Moreover, the bispecific PD1-NP-PDL1 could bind with both the activated T cells and the PD-L1-expressing tumor cells, and tether the two type of cells together. Functionally, aptamer-modified nanoparticles exhibited stronger immune-stimulating effects vs. free aptamers. Specifically, PD1-NP or PDL1-NP induced stronger lymphocyte-mediated cytotoxicity against PD-L1-expressing tumor cells in vitro vs. free PD-1 or PD-L1 aptamers. Animal studies also showed that PD1-NP or PDL1-NP significantly improved antitumor efficacy against CT26 colon cancer in vivo vs. free PD-1 or PD-L1 aptamers. Importantly, the bispecific PD1-NP-PDL1 further boosted the in vivo antitumor efficacy compared with PD1-NP or PDL1-NP, without raising systemic toxicity. Conclusion The results suggest that the bispecific PD1-NP-PDL1 is a promising nanotherapeutic to improve the efficacy of PD-1/PD-L1 blockade, and may have application potential in colon cancer treatment.https://doi.org/10.1186/s12645-023-00239-xAptamersAlbuminNanoparticlesImmunotherapyPD-1PD-L1 |
| spellingShingle | Qiping Jiang Fengjiao Yao Yacong An Xialian Lai Xundou Li Zhen Yu Xian-Da Yang Novel nanotherapeutics for cancer immunotherapy by albumin nanoparticles functionalized with PD-1 and PD-L1 aptamers Cancer Nanotechnology Aptamers Albumin Nanoparticles Immunotherapy PD-1 PD-L1 |
| title | Novel nanotherapeutics for cancer immunotherapy by albumin nanoparticles functionalized with PD-1 and PD-L1 aptamers |
| title_full | Novel nanotherapeutics for cancer immunotherapy by albumin nanoparticles functionalized with PD-1 and PD-L1 aptamers |
| title_fullStr | Novel nanotherapeutics for cancer immunotherapy by albumin nanoparticles functionalized with PD-1 and PD-L1 aptamers |
| title_full_unstemmed | Novel nanotherapeutics for cancer immunotherapy by albumin nanoparticles functionalized with PD-1 and PD-L1 aptamers |
| title_short | Novel nanotherapeutics for cancer immunotherapy by albumin nanoparticles functionalized with PD-1 and PD-L1 aptamers |
| title_sort | novel nanotherapeutics for cancer immunotherapy by albumin nanoparticles functionalized with pd 1 and pd l1 aptamers |
| topic | Aptamers Albumin Nanoparticles Immunotherapy PD-1 PD-L1 |
| url | https://doi.org/10.1186/s12645-023-00239-x |
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