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Published on: May 22, 2020
Magnetically Navigated and PSMA/STEAP1 Dual-Targeted Nanoliposomes for NIR-II/MRI Imaging with
Jian-Xuan Sun1, Ye An2, Si-Han Zhang1
1Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Precision theranostics for castration-resistant prostate cancer remain a major challenge because of tumor heterogeneity, drug toxicity, and resistance to conventional therapies. Here, we report a multifunctional theranostic nanoplatform that integrates multimodal imaging guidance, dual-targeted delivery, photothermal therapy, and immune activation for the precision treatment of prostate cancer. By encapsulating aggregation-induced emission luminogens and magnetic nanoparticles, this system achieves superior second near-infrared fluorescence and magnetic resonance imaging fusion for deep-tissue visualization. The dual-targeting strategy, which integrates magnetic navigation with simultaneous engagement of six-transmembrane epithelial antigen of the prostate 1 and prostate specific membrane antigen (PSMA), effectively addresses tumor heterogeneity by enabling externally guided and biologically specific delivery to both PSMA+ and PSMA- prostate cancer cells. Upon targeted delivery, the synergistic combination of photothermal therapy and chemotherapy achieves potent tumor growth inhibition, activates CD8+ T cells and macrophages to promote robust antitumor immune responses, and elicits durable immunological memory to prevent tumor recurrence. In vitro and in vivo studies demonstrate superior tumor targeting specificity, enhanced imaging contrast, and minimal off-target toxicity. This study provides novel insights into the construction of a multifunctional theranostic nanoplatform in precision oncology, with promising translational potential for clinical management of castration-resistant prostate cancer.
Insights
This study presents a novel nanoplatform for treating castration-resistant prostate cancer. It combines advanced imaging, targeted drug delivery, and immunotherapy to overcome treatment challenges and improve patient outcomes.
Area of Science:
- Oncology
- Nanotechnology
- Immunotherapy
Background:
- Castration-resistant prostate cancer (CRPC) presents significant treatment challenges due to tumor heterogeneity, drug toxicity, and therapy resistance.
- Current therapeutic strategies often lack specificity and efficacy in advanced stages of prostate cancer.
Purpose of the Study:
- To develop a multifunctional theranostic nanoplatform for precision treatment of CRPC.
- To integrate multimodal imaging, dual-targeted delivery, photothermal therapy, and immune activation into a single system.
Main Methods:
- Encapsulation of aggregation-induced emission luminogens and magnetic nanoparticles for multimodal imaging (NIRF and MRI).
- Dual-targeting strategy involving magnetic navigation and simultaneous targeting of six-transmembrane epithelial antigen of the prostate 1 and prostate specific membrane antigen (PSMA).
- Synergistic application of photothermal therapy and chemotherapy, coupled with immune activation (CD8+ T cells and macrophages).
Main Results:
- Achieved superior deep-tissue visualization through fused NIRF and MRI.
- Demonstrated effective, externally guided, and biologically specific delivery to both PSMA+ and PSMA- prostate cancer cells, addressing tumor heterogeneity.
- Showcased potent tumor growth inhibition, robust antitumor immune responses, and durable immunological memory.
- Exhibited enhanced tumor targeting specificity, improved imaging contrast, and minimal off-target toxicity in vitro and in vivo.
Conclusions:
- The developed multifunctional theranostic nanoplatform offers a promising approach for precision oncology in CRPC.
- This system effectively overcomes key challenges in CRPC treatment, including heterogeneity and resistance.
- The study highlights the translational potential of advanced nanotheranostics for clinical application in prostate cancer management.
