ATP-Responsive Smart Hydrogel Releasing Immune Adjuvant Synchronized with Repeated Chemotherapy or Radiotherapy to...

Area of Science:

• Biomedical Engineering
• Cancer Immunology
• Drug Delivery Systems

Background:

• Chemotherapeutics and ionizing radiation can induce immunogenic cell death (ICD), a process that can be amplified by immune adjuvants.
• Clinical cancer therapies often involve repeated low-dose treatments, making concurrent adjuvant administration impractical.
• Developing strategies to synchronize adjuvant release with these repeated treatments is crucial for enhancing antitumor immunity.

Purpose of the Study:

• To develop a smart hydrogel capable of releasing immune adjuvants in response to repeated low-dose chemo-/radiotherapies.
• To investigate the synergistic effects of this hydrogel-based immunotherapy on tumor elimination and immune memory.
• To evaluate the potential of this strategy in inhibiting distant tumor metastases, particularly in combination with immune checkpoint blockade.

Main Methods:

• An alginate-based hydrogel was engineered, conjugated with an adenosine triphosphate (ATP)-specific aptamer hybridized with a CpG oligonucleotide.
• The hydrogel was designed to release CpG adjuvants upon detection of ATP released from chemo-/radiotherapy-induced immunogenic cell death.
• The efficacy of the smart hydrogel was evaluated in established tumor models, assessing tumor elimination, immune memory, and inhibition of distant metastases.

Main Results:

• The smart hydrogel successfully released immune adjuvants (CpG) in synchrony with low-dose oxaliplatin or X-ray treatments.
• This synchronized release led to remarkable synergistic responses, effectively eliminating established tumors and generating long-lasting immune memory.
• Combined therapy demonstrated inhibition of distant tumor metastases, especially when integrated with immune checkpoint blockade.

Conclusions:

• A conceptually novel strategy was presented for cancer immunotherapy, aligning adjuvant release with repeated low-dose chemo-/radiotherapy.
• The developed smart hydrogel offers a clinically relevant approach to enhance antitumor immunity and combat tumor recurrence and metastasis.
• This innovative method holds significant promise for improving the efficacy of cancer treatment regimens.