Strongly quenched activatable theranostic nanogel for precision imaging-guided photodynamic therapy and enhanced

Yan Li1, Hyeri Lee1, Eun Mi Go1

  • 1Research Institute, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi-Do 10408, Republic of Korea.

Insights

A novel nanogel (NATNgel) enables precise imaging-guided photodynamic therapy (PDT) and enhances immunotherapy for rapidly growing tumors. This combination therapy achieved complete tumor regression with no observed side effects.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Immunotherapy

Background:

  • Immune checkpoint inhibitors (ICIs) show limited efficacy in large or rapidly growing tumors.
  • High costs and limitations necessitate novel strategies to improve ICI therapeutic efficacy.
  • Developing safe and effective combination therapies is crucial for cancer treatment.

Purpose of the Study:

  • To develop an activatable theranostic nanogel (NATNgel) for precision imaging-guided photodynamic therapy (PDT) and immunotherapy.
  • To evaluate NATNgel's capability for image-guided PDT in vivo.
  • To assess the combined efficacy of NATNgel-mediated PDT and anti-PD-1 immunotherapy against rapidly growing tumors.

Main Methods:

  • Synthesis and characterization of near-infrared (NIR) fluorescent dye-loaded activatable theranostic nanogel (NATNgel).
  • In vivo NIR fluorescence imaging for tumor visualization and image-guided PDT.
  • Combination therapy using NATNgel-mediated PDT and anti-PD-1 antibody treatment.
  • Histopathological evaluation and blood chemistry analysis to assess treatment safety and efficacy.

Main Results:

  • NATNgel demonstrated selective activation of NIR fluorescence and phototoxicity within tumor cells.
  • High tumor-to-background ratio (7.31 ± 1.40) achieved in vivo, enabling real-time image-guided PDT.
  • Combined PDT and anti-PD-1 therapy resulted in complete tumor regression and suppressed tumor regrowth upon rechallenge.
  • No significant side effects observed in major organs or blood chemistry.

Conclusions:

  • NATNgel is a safe and effective theranostic material for precision imaging-guided PDT.
  • The combination of NATNgel-PDT and immunotherapy significantly enhances anti-tumor efficacy.
  • This approach holds promise for improving cancer treatment outcomes, particularly for challenging tumors.

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