A Laser-Activated Biocompatible Theranostic Nanoagent for Targeted Multimodal Imaging and Photothermal Therapy
Liming Deng1, Xiaojun Cai2, Danli Sheng1
1Institute of Ultrasound Imaging & Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Ultrasound Molecular Imaging, 400010 Chongqing P. R. China.
Abstract:
Multifunctional nanoparticles have been reported for cancer detection and treatment currently. However, the accurate diagnosis and efficient treatment for tumors are still not satisfied. Here we report on the development of targeted phase change multimodal polymeric nanoparticles for the imaging and treatment of HER2-positive breast cancer.
Methods:
We evaluated the multimodal imaging capabilities of the prepared nanoparticles in vitro using agar-based phantoms. The targeting performance and cytotoxicity of the nanoparticles were examined in cell culture using SKBR3 (over-expressing HER2) and MDA-MB-231 (HER2 negative) cells. We then tested the magnetic resonance (MR)/ photoacoustic (PA)/ ultrasound (US)/ near-infrared fluorescence (NIRF) multimodal imaging properties and photothermal effect of the nanoparticles in vivo using a SKBR3 breast xenograft model in nude mice. Tissue histopathology and immunofluorescence were also conducted.
Results:
Both in vitro and in vivo systematical studies validated that the hybrid nanoparticles can be used as a superb MR/US/PA/NIRF contrast agent to simultaneously diagnose and guide tumor photothermal therapy (PTT). When irradiated by a near infrared laser, the liquid PFP vaporizes to a gas, rapidly expelling the contents and damaging surrounding tissues. The resulting micro-sized bubbles provide treatment validation through ultrasound imaging. Localization of DIR and SPIO in the tumor region facilitate photothermal therapy for targeted tumor destruction. The mice treated with HER2 targeted nanoparticles had a nearly complete response to treatment, while the controls showed continued tumor growth.
Conclusion:
This novel theranostic agent may provide better diagnostic imaging and therapeutic potential than current methods for treating HER2-positive breast cancer.
Insights
New targeted nanoparticles offer advanced imaging and treatment for HER2-positive breast cancer. These multimodal nanoparticles enable simultaneous diagnosis and photothermal therapy, showing significant tumor reduction in preclinical models.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Current multifunctional nanoparticles for cancer diagnosis and treatment show limitations in accuracy and efficiency.
- Accurate diagnosis and effective treatment of tumors remain significant clinical challenges.
Purpose of the Study:
- To develop targeted phase-change multimodal polymeric nanoparticles for imaging and treating HER2-positive breast cancer.
- To create a theranostic agent combining multimodal imaging with photothermal therapy.
Main Methods:
- In vitro evaluation of nanoparticle imaging capabilities using phantoms.
- In vitro assessment of targeting and cytotoxicity in HER2-positive (SKBR3) and HER2-negative (MDA-MB-231) cells.
- In vivo testing of multimodal imaging (MR/PA/US/NIRF) and photothermal effects in a HER2-positive breast cancer xenograft mouse model.
Main Results:
- Nanoparticles demonstrated superb in vitro and in vivo multimodal imaging (MR/US/PA/NIRF) capabilities.
- Photothermal therapy using nanoparticles led to targeted tumor destruction and significant tumor response in mice.
- Ultrasound imaging validated treatment by visualizing micro-bubbles generated during therapy.
Conclusions:
- The developed theranostic nanoparticles offer enhanced diagnostic imaging and therapeutic potential for HER2-positive breast cancer.
- This approach may surpass current diagnostic and therapeutic methods for this cancer type.
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