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Strongly quenched activatable theranostic nanogel for precision imaging-guided photodynamic therapy and enhanced
Abstract:
Immune checkpoint inhibitors (ICIs) are innovative immunotherapeutic agents for cancer. However, their low therapeutic efficacy in patients with large or rapidly growing tumors, along with their high cost, represents a notable limitation in their clinical applications. Therefore, new and safe strategies must be developed to enhance the therapeutic efficacy of ICIs in clinical settings. In this study, we developed a near-infrared (NIR) fluorescent dye-loaded activatable theranostic nanogel (NATNgel) for precision imaging-guided photodynamic therapy (PDT) and combined immunotherapy for rapidly growing tumors. Although NIR fluorescence and phototoxicity of NATNgel are strongly quenched, these can be selectively activated inside target tumor cells. A high tumor-to-background ratio (7.31 ± 1.40) in NIR fluorescence imaging could be achieved in NATNgel-treated mice, enabling real-time image-guided PDT. The combination of PDT and anti-PD-1 antibody therapy resulted in complete tumor regression. Histopathological evaluation of major organs and blood chemistry analysis revealed no side effects of the combined treatment regimen. In addition, the combination treatment completely suppressed the growth of rechallenged tumors. Overall, NATNgel is a safe and promising theranostic material for precision imaging-guided PDT and enhanced immunotherapy.
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.

