Reinvigorating CD8+ T cells through ADRB1 blockade using copper-propranolol nanoparticles for enhanced immune checkpoint blockade therapy

Sep 23, 2026

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Colorectal cancer ranks third globally for incidence and second for mortality, and immunotherapy efficacy remains constrained by an immunosuppressive tumor microenvironment driven in part by T cell exhaustion. A copper–propranolol nanoplatform (Cu-PN NPs) was engineered by coordinating copper ions with propranolol and stabilizing the complex via mPEG-SH self-assembly. It codelivers copper ions and propranolol to induce cuproptosis and apoptosis for immunogenic cell death, while blocking ADRB1 to reverse exhaustion. In CRC cell lines and patient-derived organoids, the platform enhances cytotoxicity and ICD versus monotherapy, inhibits tumor growth, restores TME function by reducing exhaustion, and boosts dendritic maturation and CD8+ activation, with improved control combined with anti-PD-1 therapy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Introduction

Immunogenic cell death and T cell exhaustion

Therapeutic strategy overview

Cu-PN NPs construction and dual functions

Experimental evaluation

In vitro studies and ICD induction

In vivo antitumor effects and combination with anti-PD-1

Weng et al. Journal of Nanobiotechnology (2026) 24:24 [https://doi.org/10.1186/s12951-025-03924-8](https://doi.org/10.1186/s12951-025-03924-8) Journal of Nanobiotechnology RESEARCH Open Access Reinvigorating CD8+ T cells through ADRB1 blockade using copper-propranolol nanoparticles for enhanced immune checkpoint blockade therapy Binshu Weng1†, Nan Zhu1,2†, Huirong Li3†, Lishan Ding2†, Yutong Wu1, Ying Chen1, Yijie Xi1, Lifan Lin 1, Jiawen Chen1, Le Xin4, Jinjun Ye3,4*, Yanfeng Hu1*, Guoxin Li1,2* and Weihong Guo1* Abstract Currently, colorectal cancer ranks third in terms of global cancer incidence and second in terms of cancer-related mortality, posing a significant therapeutic challenge. However, the efficacy of immunotherapy is limited by the immunosuppressive tumor microenvironment, which is driven in part by T cell exhaustion. Herein, a copper– propranolol nanoplatform (Cu-PN NPs) rationally engineered by coordinating copper ions with propranolol and stabilizing the complex via mPEG-SH self-assembly was initially constructed. This design enables the codelivery of copper ions and propranolol, achieving dual functions: inducing copper-dependent cell death (cuproptosis) and apoptosis to trigger immunogenic cell death (ICD), and blocking ADRB1 on T cells to reverse exhaustion and restore effector function. In vitro studies in CT26 colorectal cancer (CRC) cells and patient-derived organoids (PDOs) confirmed enhanced cytotoxicity and ICD induction compared with those of monotherapy. In vivo, Cu-PN NPs significantly inhibited CRC tumour growth, reshaped the tumour microenvironment (TME) by attenuating T cell exhaustion, increasing cytokine secretion, and promoting dendritic cell maturation and CD8⁺ T cell activation. When combined with anti-PD-1 therapy, Cu-PN NPs markedly improved tumour control. This work introduces Cu-PN NPsas a dual-functional nanoplatform that integrates ICD induction with T cell reinvigoration via ADRB1 blockade, offering a promising strategy to enhance immune checkpoint blockade therapy against colorectal cancer. †Binshu Weng, Nan Zhu, Huirong Li and Lishan Ding contributed equally. *Correspondence: Jinjun Ye[yejj610@163.com](yejj610@163.com)[ ](yejj610@163.com)Yanfeng Hu[banby@smu.edu.cn](banby@smu.edu.cn)[ ](banby@smu.edu.cn)Guoxin Li[lgxa04510@btch.edu.cn](lgxa04510@btch.edu.cn)[ ](lgxa04510@btch.edu.cn)Weihong Guo[gwh2823@smu.edu.cn](gwh2823@smu.edu.cn) Full list of author information is available at the end of the article © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/](vecommons.org/licenses/by-nc-nd/4.0/.)[.](vecommons.org/licenses/by-nc-nd/4.0/.) Weng et al. Journal of Nanobiotechnology (2026) 24:24 Page 2 of 18 Keywords Copper-propranolol nanoparticles, Colorectal cancer, Cuproptosis, ADRB1, T cell exhaustion, Immunotherapy Graphical Abstract Introduction Colorectal cancer (CRC) is the third most common malignant tumor in the world, and its mortality is the second highes

FAQs

What problem does the study address in colorectal cancer immunotherapy?

The study targets limited immunotherapy efficacy caused by an immunosuppressive tumor microenvironment, where T cell exhaustion reduces effective immune responses.

How do Cu-PN NPs work to enhance immune checkpoint blockade therapy?

Cu-PN NPs codeliver copper ions and propranolol to induce cuproptosis and apoptosis, promoting immunogenic cell death, and they block ADRB1 on T cells to reverse exhaustion and restore effector function.

What evidence supports the platform’s performance in the paper?

In vitro experiments in CT26 colorectal cancer cells and patient-derived organoids show improved cytotoxicity and enhanced ICD, and in vivo results demonstrate tumor growth inhibition and reshaping of the tumor microenvironment, with better tumor control when combined with anti-PD-1 therapy.

Sep 23, 2026

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