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Updated: Aug 4, 2025
Injectable Supramolecular Polymer-Nanoparticle Hydrogels for Cell and Drug Delivery Applications
Published on: February 7, 2021
DNA Hydrogel-Based Nanocomplexes with Cancer-Targeted Delivery and Light-Triggered Peptide Drug Release for
Mohzibudin Z Quazi1, Nokyoung Park1
1Department of Chemistry and The Natural Science Research Institute, 116 Myongji-ro, Yongin, Gyeonggi-do 17058, Republic of Korea.
Abstract:
Cancer therapies based on chemotherapeutic drug delive ries have been the most facilitated studies. Recently, peptide drugs have emerged as anticancer drugs due to their less immunogenicity and lower production costs compared with other synthetics. However, still, the side effects of these chemotherapeutics on healthy tissues have been a great concern to deal with, and these side effects are usually caused by off-targeted delivery and unwanted leakage. In addition, peptides are easily degraded by enzyme attacks during delivery. To address these concerns, here, we developed a robust, cancer-specific peptide drug delivery system with negligible cytotoxicity in in vitro. A peptide drug delivery vehicle (Dgel-PD-AuNP-YNGRT) was constructed by stepwise functionalization on a nanoscale DNA hydrogel (Dgel). A cell-penetrating anticancer peptide drug, Buforin IIb, was loaded within the Dgel network via electrostatic attraction followed by AuNP assembly. The AuNPs were employed as photothermal reagents for light-triggered peptide drug release. An additional peptide, including a cancer-targeting YNGRT sequence, was also bound on the Dgel for cancer-cell-targeted delivery. According to the results obtained from the studies employing cancer cells as well as normal cells, Dgel-PD-AuNP-YNGRT nanocomplexes could be delivered specifically to cancer cells, activated by light illumination, and release anticancer peptide drugs to kill cancer cells with no cytotoxicity and negligible hazardous effect on normal cell lines. The obtained cell viability assay suggests that at a high intensity (15 W/cm2), photothermally triggered released peptide drug has shown up to 44% higher kill than only peptide drug treatments in cancer cells. Similarly, the Bradford assay demonstrated that up to 90% of peptide drugs were released with our engineered Dgel-PD-AuNP-YNGRT nanocomplex. The Dgel-PD-AuNP-YNGRT nanocomplex may serve as an ideal anticancer peptide drug delivery platform for safe, cancer-specific targeting and efficient peptide drug delivery in cancer therapy.
Insights
This study presents a novel DNA hydrogel nanoparticle system for targeted cancer therapy. The system safely delivers peptide drugs to cancer cells, enhancing their efficacy with light-triggered release and minimizing harm to healthy tissues.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Drug Delivery Systems
Background:
- Chemotherapeutic drug delivery remains a focus in cancer therapy.
- Peptide drugs offer advantages over synthetics but face challenges like immunogenicity and degradation.
- Off-targeted delivery and leakage of chemotherapeutics cause significant side effects on healthy tissues.
Purpose of the Study:
- To develop a robust, cancer-specific peptide drug delivery system with minimal cytotoxicity.
- To engineer a nanoscale DNA hydrogel vehicle for controlled and targeted drug release.
- To enhance the efficacy of peptide anticancer drugs through photothermal activation.
Main Methods:
- Constructed a DNA hydrogel-based vehicle (Dgel-PD-AuNP-YNGRT) functionalized with a cancer-targeting peptide.
- Loaded the cell-penetrating anticancer peptide Buforin IIb into the hydrogel network.
- Utilized gold nanoparticles (AuNPs) for photothermal drug release triggered by light illumination.
Main Results:
- The Dgel-PD-AuNP-YNGRT nanocomplex demonstrated specific delivery to cancer cells.
- Light activation triggered the release of peptide drugs, leading to cancer cell death with negligible cytotoxicity to normal cells.
- Photothermally triggered drug release showed up to 44% higher cancer cell kill compared to peptide drugs alone.
- Up to 90% of peptide drugs were successfully released from the engineered nanocomplex.
Conclusions:
- The developed Dgel-PD-AuNP-YNGRT nanocomplex is a promising platform for safe and effective cancer therapy.
- This system enables cancer-specific targeting and controlled drug release, overcoming limitations of traditional peptide drug delivery.
- The combination of nanotechnology and photothermal activation offers a new strategy for enhancing anticancer peptide drug efficacy.
