A TME-activated Nano-catalyst for Triple Synergistic Therapy of Colorectal Cancer

Overview

Journal Sci Rep

Specialty Science

Date 2024 Feb 9

PMID 38336997

Authors

Qiang Liu

Yurong Xiang

Qiang Yu

Quan Lv

Zheng Xiang

Affiliations

Soon will be listed here.

Abstract

Colorectal cancer cells are highly heterogeneous and exhibit various drug resistances, making personalized treatment necessary. This typically involves a combination of different treatment modalities such as surgery, radiation, and chemotherapy to increase patient survival. Inspired by this, synergistic therapy, which combines multiple modalities into a single nanotherapeutic drug, shows promise in treating cancer. In this study, a nano-catalyst based on calcium peroxide (CaO) and the chemotherapeutic drug doxorubicin hydrochloride (DOX) co-loaded into HPB nanoparticles (HPB@CaO/DOX-PAA) was developed to achieve synergistic cancer treatment through chemodynamic/chemo/photothermal (CDT/CT/PTT) mechanisms. After being endocytosed by cancer cells, the nano-catalyst decomposes, releasing cargo. During near-infrared light irradiation, HPB induces a photothermal effect, DOX exhibits significant RNA and DNA destruction capabilities, meanwhile CaO produces a large amount of HO in the moderately acidic TME, which combines with Fe ions derived from HPB to form the highly toxic •OH in a Fenton-like reaction, enhancing the chemodynamic treatment. Assays conducted ex vivo and in vivo have exhibited the efficacy of this triple synergistic therapeutic regimen, indicating its potential clinical application.

Citing Articles

An analytical review of the therapeutic application of recent trends in MIL-based delivery systems in cancer therapy.

Beiranvand M, Dehghan G Mikrochim Acta. 2025; 192(2):89.

PMID: 39821354 DOI: 10.1007/s00604-024-06944-7.

References

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Arnold M, Sierra M, Laversanne M, Soerjomataram I, Jemal A, Bray F . Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2016; 66(4):683-691. DOI: 10.1136/gutjnl-2015-310912. View

Salgia R, Kulkarni P . The Genetic/Non-genetic Duality of Drug 'Resistance' in Cancer. Trends Cancer. 2018; 4(2):110-118. PMC: 5822736. DOI: 10.1016/j.trecan.2018.01.001. View

Massague J, Obenauf A . Metastatic colonization by circulating tumour cells. Nature. 2016; 529(7586):298-306. PMC: 5029466. DOI: 10.1038/nature17038. View

Zhao P, Li H, Bu W . A Forward Vision for Chemodynamic Therapy: Issues and Opportunities. Angew Chem Int Ed Engl. 2023; 62(7):e202210415. DOI: 10.1002/anie.202210415. View

Zheng Q, Liu X, Zheng Y, Yeung K, Cui Z, Liang Y . The recent progress on metal-organic frameworks for phototherapy. Chem Soc Rev. 2021; 50(8):5086-5125. DOI: 10.1039/d1cs00056j. View

Pham T, Nguyen V, Choi Y, Lee S, Yoon J . Recent Strategies to Develop Innovative Photosensitizers for Enhanced Photodynamic Therapy. Chem Rev. 2021; 121(21):13454-13619. DOI: 10.1021/acs.chemrev.1c00381. View

Zhen W, An S, Wang S, Hu W, Li Y, Jiang X . Precise Subcellular Organelle Targeting for Boosting Endogenous-Stimuli-Mediated Tumor Therapy. Adv Mater. 2021; 33(51):e2101572. DOI: 10.1002/adma.202101572. View

Wan S, Zeng J, Cheng H, Zhang X . ROS-induced NO generation for gas therapy and sensitizing photodynamic therapy of tumor. Biomaterials. 2018; 185:51-62. DOI: 10.1016/j.biomaterials.2018.09.004. View

10.

Tian Q, An L, Tian Q, Lin J, Yang S . Ellagic acid-Fe@BSA nanoparticles for endogenous HS accelerated Fe(III)/Fe(II) conversion and photothermal synergistically enhanced chemodynamic therapy. Theranostics. 2020; 10(9):4101-4115. PMC: 7086347. DOI: 10.7150/thno.41882. View

11.

Wang Q, Qu B, Li J, Liu Y, Dong J, Peng X . Multifunctional MnO/AgSbS Nanotheranostic Agent for Single-Laser-Triggered Tumor Synergistic Therapy in the NIR-II Biowindow. ACS Appl Mater Interfaces. 2022; 14(4):4980-4994. DOI: 10.1021/acsami.1c21752. View

12.

Tang Z, Liu Y, He M, Bu W . Chemodynamic Therapy: Tumour Microenvironment-Mediated Fenton and Fenton-like Reactions. Angew Chem Int Ed Engl. 2018; 58(4):946-956. DOI: 10.1002/anie.201805664. View

13.

Qian X, Zhang J, Gu Z, Chen Y . Nanocatalysts-augmented Fenton chemical reaction for nanocatalytic tumor therapy. Biomaterials. 2019; 211:1-13. DOI: 10.1016/j.biomaterials.2019.04.023. View

14.

Lin L, Song J, Song L, Ke K, Liu Y, Zhou Z . Simultaneous Fenton-like Ion Delivery and Glutathione Depletion by MnO -Based Nanoagent to Enhance Chemodynamic Therapy. Angew Chem Int Ed Engl. 2018; 57(18):4902-4906. DOI: 10.1002/anie.201712027. View

15.

Zhang L, Lu H, Tang Y, Lu X, Zhang Z, Zhang Y . Calcium-peroxide-mediated cascades of oxygen production and glutathione consumption induced efficient photodynamic and photothermal synergistic therapy. J Mater Chem B. 2023; 11(13):2937-2945. DOI: 10.1039/d2tb02776c. View

16.

Liu B, Bian Y, Liang S, Yuan M, Dong S, He F . One-Step Integration of Tumor Microenvironment-Responsive Calcium and Copper Peroxides Nanocomposite for Enhanced Chemodynamic/Ion-Interference Therapy. ACS Nano. 2021; 16(1):617-630. DOI: 10.1021/acsnano.1c07893. View

17.

Chen X, Fan X, Zhang Y, Wei Y, Zheng H, Bao D . Cooperative coordination-mediated multi-component self-assembly of "all-in-one" nanospike theranostic nano-platform for MRI-guided synergistic therapy against breast cancer. Acta Pharm Sin B. 2022; 12(9):3710-3725. PMC: 9513557. DOI: 10.1016/j.apsb.2022.02.027. View

18.

Li X, Lovell J, Yoon J, Chen X . Clinical development and potential of photothermal and photodynamic therapies for cancer. Nat Rev Clin Oncol. 2020; 17(11):657-674. DOI: 10.1038/s41571-020-0410-2. View

19.

Wu J, Williams G, Niu S, Yang Y, Li Y, Zhang X . Biomineralized Bimetallic Oxide Nanotheranostics for Multimodal Imaging-Guided Combination Therapy. Theranostics. 2020; 10(2):841-855. PMC: 6929990. DOI: 10.7150/thno.40715. View

20.

Busquets M, Estelrich J . Prussian blue nanoparticles: synthesis, surface modification, and biomedical applications. Drug Discov Today. 2020; 25(8):1431-1443. DOI: 10.1016/j.drudis.2020.05.014. View