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Updated: Jul 10, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Prominence of bioresponsive DNA nanococoons in tackling post-surgery cancer recurrence
Sravani Yerram1, Ramesh Joga1, Pooja Shende1
1Department of Regulatory Affairs, National Institute Pharmaceutical Education & Research (NIPER)-Hyderabad, Telangana, 500037, India.
Abstract:
Post-surgery cancer recurrence is one of the reasons for increased cancer cases. The effective usage of the enhanced permeability and retention effect of a nanocarrier infused with the bioresponsive release mechanism of checkpoint inhibitors (aPD1 and aCTLA4) can become a boon to mankind. DNA nanococoons (DNCs) comprising cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODNs) with potent immunostimulatory effects can significantly enhance anti-cancer activity. Triglycerylmonostearate (TGMS) with enzymatic cleavage potential at the wound sites of tumor resection, upon caging with restriction enzyme (HhaI) followed by attaching to DNCs, makes the immunotherapy bioresponsive. Hhal-TGMS-DNCs-aPD1 triggered by the inflammation at the wound site undergoes enzymatic cleavage, releases the restriction enzyme, converts DNCs to CpG ODNs sequentially and with sustained aPD1 release exerts an appreciable anti-cancer effect.
Insights
This study introduces a novel nanocarrier system for cancer immunotherapy. The DNA nanococoon (DNC) system effectively delivers checkpoint inhibitors, enhancing anti-cancer activity and reducing recurrence after surgery.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Immunotherapy
Background:
- Post-surgery cancer recurrence remains a significant challenge, contributing to increased cancer incidence.
- Nanocarrier systems offer potential for targeted drug delivery, leveraging the enhanced permeability and retention (EPR) effect.
- Checkpoint inhibitors, such as anti-PD1 (aPD1) and anti-CTLA4 (aCTLA4), are crucial in cancer immunotherapy.
Purpose of the Study:
- To develop a bioresponsive nanocarrier system for enhanced cancer immunotherapy post-surgery.
- To investigate the efficacy of DNA nanococoons (DNCs) loaded with immunostimulatory CpG-ODNs and checkpoint inhibitors.
- To create a system that releases therapeutic agents in response to the tumor microenvironment.
Main Methods:
- DNA nanococoons (DNCs) were engineered to encapsulate cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODNs) for immunostimulation.
- Triglycerylmonostearate (TGMS), modified with the restriction enzyme HhaI, was attached to DNCs to create a bioresponsive system (HhaI-TGMS-DNCs).
- The nanocarrier system was loaded with anti-PD1 (aPD1) antibodies for targeted immunotherapy.
Main Results:
- The HhaI-TGMS-DNCs-aPD1 system demonstrated enzymatic cleavage triggered by inflammation at tumor resection sites.
- This cleavage sequentially released the restriction enzyme, converted DNCs to CpG-ODNs, and enabled sustained release of aPD1.
- The engineered nanocarrier system exhibited significant anti-cancer effects, addressing post-surgery recurrence.
Conclusions:
- The developed HhaI-TGMS-DNCs-aPD1 nanocarrier system represents a promising strategy for combating post-surgery cancer recurrence.
- Bioresponsive drug delivery systems can significantly enhance the efficacy of cancer immunotherapy.
- This approach holds potential for improving patient outcomes by targeting cancer recurrence effectively.
