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Activatable Immunotheranostic Nanovesicles for Coordinated Phagocytic Reprogramming and Real-Time Immune Monitoring.

Yuan Zhang1, Lu Zhang2, Shuxuan Yang1

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This study introduces a novel nanoplatform for cancer immunotherapy that reprograms immune cells and monitors their activity in real-time. This approach enhances anti-tumor responses and establishes long-term immune memory against solid tumors.

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Area of Science:

  • Oncology
  • Immunology
  • Nanotechnology
  • Biomedical Engineering

Background:

  • Solid tumor immunotherapy faces challenges due to impaired immune cells in the tumor microenvironment.
  • Existing treatments struggle with immune cell dysfunction and phenotypic alterations within tumors.

Purpose of the Study:

  • To develop a multifunctional nanoplatform for precise immunomodulation and dynamic immune monitoring in cancer therapy.
  • To overcome limitations in current cancer immunotherapy efficacy against solid tumors.

Main Methods:

  • Engineered cell-derived nanovesicles displaying anti-CD47 nanobodies and calreticulin signals to modulate immune responses.
  • Utilized a pH-responsive tannic acid-manganese (TA-Mn) shell for systemic stability and tumor-selective activation.
  • Integrated a nitric oxide-activatable photoacoustic probe for real-time visualization of macrophage repolarization.

Main Results:

  • The nanoplatform promoted tumor cell phagocytosis and dendritic cell (DC) maturation by blocking the CD47-SIRPα axis and providing 'eat me' cues.
  • Activated the cGAS-STING pathway, enhanced DC activation, antigen cross-presentation, and reprogrammed macrophages to an M1 phenotype.
  • Achieved significant tumor eradication, prevention of metastasis, and long-term immune protection in murine models.

Conclusions:

  • The developed nanoplatform offers a versatile and adaptive immunotherapeutic strategy by combining activatable theranostics with immune reprogramming.
  • This approach represents a significant advancement in precision cancer immunotherapy, enhancing anti-tumor immunity and memory.
  • The study highlights the potential of integrated immune reprogramming and monitoring for improved cancer treatment outcomes.