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Tumor Cell Targeting and Responsive Nanoplatform for Multimodal-Imaging Guided Chemodynamic/Photodynamic/Photothermal
Lihong Li1,2,3, Jiaojiao Li1, Rongrong Hu1
1College of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030001, P. R. China.
Abstract:
Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with ineffective treatment and poor prognosis. It is in great demand to develop a novel theranostic strategy for accurate diagnosis and targeted treatment of TNBC. In the present study, one nanoplatform (HA-ICG-Fe-PDA), endowed with multimodal imaging-guided chemodynamic/photodynamic/photothermal (CDT/PDT/PTT) synergistic therapy capacity toward TNBC, was innovatively constructed. The nanoplatform was prepared by covalently conjugating ICG-decorated hyaluronic acid (HA) on Fe3+-chelated polydopamine (PDA). HA facilitated the targeting and accumulating of the nanoplatform in tumor tissue and cells of TNBC, thus producing enhanced magnetic resonance signal. Upon entering into TNBC cells, the intracellular hyaluronidase-catalyzed cleavage of HA-ICG-Fe-PDA activated the prequenched near-infrared (NIR) fluorescence signal, allowing for the activatable NIR fluorescence imaging. On the other hand, Fe3+ in the nanoplatform could be reduced to reactive Fe2+ in tumor microenvironment, guaranteeing efficient Fenton reaction-mediated CDT. The combination of ICG with Fe-PDA enhanced the NIR absorption of the nanoplatform so that considerable PTT/PDT and photothermal imaging were achieved under 808 nm laser irradiation. In vitro and in vivo experiments have verified that the proposed nanoplatform integrates the potential of TNBC-targeting, precise NIR fluorescence/magnetic resonance/photothermal trimodal imaging, efficient treatment via synergistic CDT/PDT/PTT, as well as excellent biocompatibility. Therefore, this multifunctional nanoplatform provides a simple and versatile strategy for imaging-guided theranostics of TNBC.
Insights
A new nanoplatform targets triple-negative breast cancer (TNBC) for diagnosis and treatment. This advanced system uses multimodal imaging and synergistic therapies (chemodynamic, photodynamic, photothermal) for effective TNBC theranostics.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its aggressive nature and poor prognosis.
- There is a critical need for innovative theranostic strategies for TNBC, combining accurate diagnosis with targeted treatment.
- Current treatment options for TNBC are limited, necessitating the development of novel approaches.
Purpose of the Study:
- To construct a multifunctional nanoplatform for imaging-guided theranostics of TNBC.
- To develop a system capable of multimodal imaging (magnetic resonance, fluorescence, photothermal) and synergistic therapy (chemodynamic, photodynamic, photothermal).
- To evaluate the efficacy and biocompatibility of the nanoplatform for TNBC treatment.
Main Methods:
- Fabrication of the HA-ICG-Fe-PDA nanoplatform by conjugating ICG-decorated hyaluronic acid (HA) onto Fe3+-chelated polydopamine (PDA).
- Utilized HA for tumor targeting and enhanced magnetic resonance imaging (MRI).
- Exploited hyaluronidase-cleavable HA for activatable fluorescence imaging and Fe3+/Fe2+ redox for chemodynamic therapy (CDT) via Fenton reaction, combined with photodynamic (PDT) and photothermal therapy (PTT) under NIR laser irradiation.
Main Results:
- The nanoplatform demonstrated effective targeting and accumulation in TNBC tissues and cells.
- Achieved activatable near-infrared (NIR) fluorescence imaging upon cellular uptake and hyaluronidase cleavage.
- Verified efficient synergistic CDT/PDT/PTT effects, leading to significant tumor inhibition in vitro and in vivo.
- Confirmed excellent biocompatibility of the nanoplatform.
Conclusions:
- The developed HA-ICG-Fe-PDA nanoplatform offers a versatile and effective strategy for TNBC theranostics.
- The platform integrates precise trimodal imaging guidance with synergistic therapeutic modalities for improved treatment outcomes.
- This approach holds promise for advancing the clinical management of triple-negative breast cancer.
