DNA Hydrogel-Based Nanocomplexes with Cancer-Targeted Delivery and Light-Triggered Peptide Drug Release for Cancer-Specific Therapeutics

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.