1. ROS-Responsive Nanoprobes for Bimodal Imaging-Guided Cancer Targeted Combinatorial Therapy.
- Author
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Jiang F, Liu S, Wang L, Chen H, Huang Y, Cao Y, Wang X, Lin M, and Zhang J
- Subjects
- Animals, Female, Humans, Mice, Cell Line, Tumor, Drug Delivery Systems methods, Prodrugs chemistry, Prodrugs pharmacokinetics, Prodrugs pharmacology, Mice, Inbred BALB C, Magnetic Iron Oxide Nanoparticles chemistry, Mice, Nude, Magnetite Nanoparticles chemistry, Drug Liberation, Nanoparticles chemistry, Optical Imaging methods, Indocyanine Green chemistry, Indocyanine Green pharmacokinetics, Doxorubicin chemistry, Doxorubicin pharmacology, Doxorubicin administration & dosage, Doxorubicin pharmacokinetics, Reactive Oxygen Species metabolism, Polylactic Acid-Polyglycolic Acid Copolymer chemistry, Photochemotherapy methods, Breast Neoplasms diagnostic imaging, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Magnetic Resonance Imaging methods
- Abstract
Purpose: Chemotherapy mediated by Reactive oxygen species (ROS)-responsive drug delivery systems can potentially mitigate the toxic side effects of chemotherapeutic drugs and significantly enhance their therapeutic efficacy. However, achieving precise targeted drug delivery and real-time control of ROS-responsive drug release at tumor sites remains a formidable challenge. Therefore, this study aimed to describe a ROS-responsive drug delivery system with specific tumor targeting capabilities for mitigating chemotherapy-induced toxicity while enhancing therapeutic efficacy under guidance of Fluorescence (FL) and Magnetic resonance (MR) bimodal imaging., Methods: Indocyanine green (ICG), Doxorubicin (DOX) prodrug pB-DOX and Superparamagnetic iron oxide (SPIO, Fe
3 O4 ) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) by double emulsification method to prepare ICG/ pB-DOX/ Fe3 O4 / PLGA nanoparticles (IBFP NPs). The surface of IBFP NPs was functionalized with mammaglobin antibodies (mAbs) by carbodiimide method to construct the breast cancer-targeting mAbs/ IBFP NPs (MIBFP NPs). Thereafter, FL and MR bimodal imaging ability of MIBFP NPs was evaluated in vitro and in vivo. Finally, the combined photodynamic therapy (PDT) and chemotherapy efficacy evaluation based on MIBFP NPs was studied., Results: The multifunctional MIBFP NPs exhibited significant targeting efficacy for breast cancer. FL and MR bimodal imaging clearly displayed the distribution of the targeting MIBFP NPs in vivo. Upon near-infrared laser irradiation, the MIBFP NPs loaded with ICG effectively generated ROS for PDT, enabling precise tumor ablation. Simultaneously, it triggered activation of the pB-DOX by cleaving its sensitive moiety, thereby restoring DOX activity and achieving ROS-responsive targeted chemotherapy. Furthermore, the MIBFP NPs combined PDT and chemotherapy to enhance the efficiency of tumor ablation under guidance of bimodal imaging., Conclusion: MIBFP NPs constitute a novel dual-modality imaging-guided drug delivery system for targeted breast cancer therapy and offer precise and controlled combined treatment options., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Jiang et al.)- Published
- 2024
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