Ca- and CGAMP-Contained Semiconducting Polymer Nanomessengers for Radiodynamic-Activated Calcium Overload and Immunotherapy

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2024 Dec 16

PMID 39679909

Authors

Danling Cheng

Libai Luo

Qin Zhang

Zheming Song

Yiduo Zhan

Wenzhi Tu

Jingchao Li

Qiming Ma

Xianchang Zeng

Affiliations

Soon will be listed here.

Abstract

Various second messengers exert some vital actions in biological systems, including cancer therapy, but the therapeutic efficacy is often need to be improved. A semiconducting polymer nanomessenger (TCa/SPN/a) consisting of two second messengers, calcium ion (Ca) and cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) for metastatic breast cancer therapy, is reported here. Such a TCa/SPN/a is constructed to exhibit X-ray response for the activatable delivery of mitochondria-targeting Ca compound and cGAMP as stimulator of interferon genes (STING) agonist. With X-ray irradiation, TCa/SPN/a could generate singlet oxygen (O) via radiodynamic effect for ablating solid tumors and improving the tumor immunogenicity by inducing immunogenic cell death (ICD). Furthermore, the released mitochondria-targeting Ca compounds show a high binging effect on mitochondria and cause reactive oxygen species (ROS) generation and mitochondria damage via calcium overload, while cGAMP boosts immunological effect through activating STING pathway. In this way, TCa/SPN/a enables a radiodynamic-activated calcium overload and immunotherapy to obviously inhibit the growths of bilateral tumors and also abolish tumor metastasis in metastatic breast cancer mouse models. This article should demonstrate the first smart dual-functional nanotherapeutic containing two second messengers for precise and specific cancer therapy.

Citing Articles

Ca- and cGAMP-Contained Semiconducting Polymer Nanomessengers for Radiodynamic-Activated Calcium Overload and Immunotherapy.

Cheng D, Luo L, Zhang Q, Song Z, Zhan Y, Tu W Adv Sci (Weinh). 2024; 12(6):e2411739.

PMID: 39679909 PMC: 11809400. DOI: 10.1002/advs.202411739.

References

Prise K, OSullivan J . Radiation-induced bystander signalling in cancer therapy. Nat Rev Cancer. 2009; 9(5):351-60. PMC: 2855954. DOI: 10.1038/nrc2603. View

Chin E, Yu C, Vartabedian V, Jia Y, Kumar M, Gamo A . Antitumor activity of a systemic STING-activating non-nucleotide cGAMP mimetic. Science. 2020; 369(6506):993-999. DOI: 10.1126/science.abb4255. View

Zheng P, Ding B, Shi R, Jiang Z, Xu W, Li G . A Multichannel Ca Nanomodulator for Multilevel Mitochondrial Destruction-Mediated Cancer Therapy. Adv Mater. 2021; 33(15):e2007426. DOI: 10.1002/adma.202007426. View

Min Y, Roche K, Tian S, Eblan M, McKinnon K, Caster J . Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy. Nat Nanotechnol. 2017; 12(9):877-882. PMC: 5587366. DOI: 10.1038/nnano.2017.113. View

Lin J, He Y, Li Y, Chen J, Liu X . Oxygen-Evolving Radiotherapy-Radiodynamic Therapy Synergized with NO Gas Therapy by Cerium-Based Rare-Earth Metal-Porphyrin Framework. Small. 2024; 20(36):e2310957. DOI: 10.1002/smll.202310957. View

Li J, Rao J, Pu K . Recent progress on semiconducting polymer nanoparticles for molecular imaging and cancer phototherapy. Biomaterials. 2017; 155:217-235. PMC: 5978728. DOI: 10.1016/j.biomaterials.2017.11.025. View

Jiang Z, He L, Yu X, Yang Z, Wu W, Wang X . Antiangiogenesis Combined with Inhibition of the Hypoxia Pathway Facilitates Low-Dose, X-ray-Induced Photodynamic Therapy. ACS Nano. 2021; 15(7):11112-11125. DOI: 10.1021/acsnano.1c01063. View

Hu H, Feng W, Qian X, Yu L, Chen Y, Li Y . Emerging Nanomedicine-Enabled/Enhanced Nanodynamic Therapies beyond Traditional Photodynamics. Adv Mater. 2021; 33(12):e2005062. DOI: 10.1002/adma.202005062. View

Huang Z, Wang Y, Yao D, Wu J, Hu Y, Yuan A . Nanoscale coordination polymers induce immunogenic cell death by amplifying radiation therapy mediated oxidative stress. Nat Commun. 2021; 12(1):145. PMC: 7794559. DOI: 10.1038/s41467-020-20243-8. View

10.

Mitchell M, Billingsley M, Haley R, Wechsler M, Peppas N, Langer R . Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov. 2020; 20(2):101-124. PMC: 7717100. DOI: 10.1038/s41573-020-0090-8. View

11.

Li J, You Z, Zhai S, Zhao J, Lu K . Mitochondria-Targeted Nanosystem Enhances Radio-Radiodynamic-Chemodynamic Therapy on Triple Negative Breast Cancer. ACS Appl Mater Interfaces. 2023; 15(18):21941-21952. DOI: 10.1021/acsami.3c02361. View

12.

Yuan P, Yang T, Liu T, Yu X, Bai Y, Zhang Y . Nanocomposite hydrogel with NIR/magnet/enzyme multiple responsiveness to accurately manipulate local drugs for on-demand tumor therapy. Biomaterials. 2020; 262:120357. DOI: 10.1016/j.biomaterials.2020.120357. View

13.

Wang F, Pu K, Li J . Activating Nanomedicines with Electromagnetic Energy for Deep-Tissue Induction of Immunogenic Cell Death in Cancer Immunotherapy. Small Methods. 2022; 7(5):e2201083. DOI: 10.1002/smtd.202201083. View

14.

Zhang Y, Wang Y, Zhu A, Yu N, Xia J, Li J . Dual-Targeting Biomimetic Semiconducting Polymer Nanocomposites for Amplified Theranostics of Bone Metastasis. Angew Chem Int Ed Engl. 2023; 63(2):e202310252. DOI: 10.1002/anie.202310252. View

15.

Slavik K, Morehouse B, Ragucci A, Zhou W, Ai X, Chen Y . cGAS-like receptors sense RNA and control 3'2'-cGAMP signalling in Drosophila. Nature. 2021; 597(7874):109-113. PMC: 8410604. DOI: 10.1038/s41586-021-03743-5. View

16.

Zhou S, Cheng F, Zhang Y, Su T, Zhu G . Engineering and Delivery of cGAS-STING Immunomodulators for the Immunotherapy of Cancer and Autoimmune Diseases. Acc Chem Res. 2023; 56(21):2933-2943. PMC: 10882213. DOI: 10.1021/acs.accounts.3c00394. View

17.

Wang X, Xuan Z, Zhu X, Sun H, Li J, Xie Z . Near-infrared photoresponsive drug delivery nanosystems for cancer photo-chemotherapy. J Nanobiotechnology. 2020; 18(1):108. PMC: 7397640. DOI: 10.1186/s12951-020-00668-5. View

18.

Sun W, Chu C, Li S, Ma X, Liu P, Chen S . Nanosensitizer-mediated unique dynamic therapy tactics for effective inhibition of deep tumors. Adv Drug Deliv Rev. 2022; 192:114643. DOI: 10.1016/j.addr.2022.114643. View

19.

Tu L, Liao Z, Luo Z, Wu Y, Herrmann A, Huo S . Ultrasound-controlled drug release and drug activation for cancer therapy. Exploration (Beijing). 2023; 1(3):20210023. PMC: 10190934. DOI: 10.1002/EXP.20210023. View

20.

Zhang Y, Li J, Pu K . Recent advances in dual- and multi-responsive nanomedicines for precision cancer therapy. Biomaterials. 2022; 291:121906. DOI: 10.1016/j.biomaterials.2022.121906. View