Issue 25, 2024, Issue in Progress

Tumor microenvironment-regulated drug delivery system combined with sonodynamic therapy for the synergistic treatment of breast cancer

Abstract

Co-loading of sonosensitizers and chemotherapeutic drugs into nanocarriers can improve the biocompatibilities, stabilities, and targeting of drugs and reduce the adverse reactions of drugs, providing a robust platform to orchestrate the synergistic interplay between chemotherapy and sonodynamic therapy (SDT) in cancer treatment. In this regard, biodegradable manganese dioxide (MnO2) has attracted widespread attention because of its unique properties in the tumor microenvironment (TME). Accordingly, herein, MnO2 nanoshells with hollow mesoporous structures (H-MnO2) were etched to co-load hematoporphyrin monomethyl ether (HMME) and doxorubicin (DOX), and DOX/HMME-HMnO2@bovine serum albumin (BSA) obtained after simple BSA modification of DOX/HMME-HMnO2 exhibited excellent hydrophilicity and dispersibility. H-MnO2 rapidly degraded in the weakly acidic TME, releasing loaded HMME and DOX, and catalysed the decomposition of H2O2 abundantly present in TME, producing oxygen (O2) in situ, significantly increasing O2 concentration and downregulating the hypoxia-inducible factor 1α (HIF-1α). After irradiation of the tumor area with low-frequency ultrasound, the drug delivery efficiency of DOX/HMME-HMnO2@BSA substantially increased, and the excited HMME generated a large amount of reactive oxygen species (ROS), which caused irreversible damage to tumor cells. Moreover, the cell death rate exceeded 60% after synergistic SDT-chemotherapy. Therefore, the pH-responsive nanoshells designed in this study can realize drug accumulation in tumor regions by responding to TME and augment SDT-chemotherapy potency for breast cancer treatment by improving hypoxia in tumors. Thus, this study provides theoretical support for the development of multifunctional nanocarriers and scientific evidence for further exploration of safer and more efficient breast cancer treatments.

Graphical abstract: Tumor microenvironment-regulated drug delivery system combined with sonodynamic therapy for the synergistic treatment of breast cancer

Article information

Article type
Paper
Submitted
21 Jan 2024
Accepted
16 May 2024
First published
31 May 2024
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2024,14, 17612-17626

Tumor microenvironment-regulated drug delivery system combined with sonodynamic therapy for the synergistic treatment of breast cancer

C. Qian, G. Zhao, M. Huo, M. Su, X. Hu, Q. Liu and L. Wang, RSC Adv., 2024, 14, 17612 DOI: 10.1039/D4RA00539B

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