Synergetic Photodynamic-Photothermal-Chemotherapy Dual Targeting Nanoplatform Effective Against Breast Cancer in-Mice Model

Na Li; Xiaochun Jiang; Wanju Zhang; Wenping Xiao; Zhaona Wu; Huirong Wang; Feng He

doi:10.2147/IJN.S428022

Synergetic Photodynamic-Photothermal-Chemotherapy Dual Targeting Nanoplatform Effective Against Breast Cancer in-Mice Model

Int J Nanomedicine. 2023 Nov 6:18:6349-6365. doi: 10.2147/IJN.S428022. eCollection 2023.

Authors

Na Li¹, Xiaochun Jiang², Wanju Zhang¹, Wenping Xiao¹, Zhaona Wu¹, Huirong Wang¹, Feng He¹

Affiliations

¹ Li Shizhen College of Traditional Chinese Medicine, Huanggang Normal University, Huanggang, 438000, People's Republic of China.
² Hubei Key Laboratory for Processing and Application of Catalytic Materials, College of Chemistry and Chemical Engineering, Huanggang Normal University, Huanggang, 438000, People's Republic of China.

Abstract

Introduction: Combined multimodal therapy for breast cancer is a promising therapeutic approach to increase treatment efficacy and reduce systemic toxicity. The present study aimed to develop a novel multifunctional drug release nanoplatform based on RGD-conjugated hyaluronic acid (HA)-functionalized copper sulfide (CuS) for activatable dual-targeted synergetic therapy against cancer.

Methods: The pH and NIR-responsive dual-targeting nanoplatform CuS:Ce6@HA:DOX@RGD was prepared, characterized, and evaluated for its stability and photodynamic and photothermal properties. The loading and release of the drug were measured at different pH values with or without laser radiation using the dialysis method. The cellular uptake of the platform specifically by the tumor cells treated with different formulations was investigated through fluorescence imaging. The in vitro and in vivo biosafety levels were assessed systematically. Finally, the antitumor efficiencies against breast cancer were assessed via in vitro and in vivo experiments.

Results: The spheroid CuS:Ce6@HA:DOX@RGD exhibited remarkable stability and monodispersity in solution. The photosensitive CuS and Ce6 could simultaneously absorb the near-infrared light efficiently to convert NIR light to fatal heat and to generate reactive oxygen species. The CuS:Ce6@HA:DOX@RGD dissociated under an acid environment, causing the release of DOX into the tumor to accelerate upon laser irradiation. The CuS:Ce6@HA:DOX@RGD exhibited target-specific and strong binding ability via a synergic CD44/αvβ₃ receptor-mediated bimodal targeting, which led to improved therapeutic efficacy. The tumor growth was effectively inhibited using synergetic photodynamic/photothermal/chemo therapy. No evident systemic toxicity was noted during treatment.

Conclusion: The newly prepared CuS:Ce6@HA:DOX@RGD has great potential as an activatable theranostic nanoplatform for efficient dual-targeted synergistic therapy against breast cancer.

Keywords: breast cancer; drug delivery; responsive nanoplatform; synergistic therapy; targeting.

MeSH terms

Animals
Cell Line, Tumor
Doxorubicin / chemistry
Doxorubicin / pharmacology
Drug Delivery Systems
Mice
Nanoparticles* / chemistry
Neoplasms* / pathology
Oligopeptides
Photochemotherapy*

Substances

Doxorubicin
Oligopeptides

Grants and funding

This work was financially supported by the National Natural Science Foundation of China (21765022), the Research Fund of Huanggang Normal University (2042023016), and the Key Research and Development Program of Hubei Province (2022BCE013).