Mimics of Host Defense Peptides Derived from Dendronized Polylysines for Antibacterial and Anticancer Therapy
Yusheng Qian1, Danjing Yang2, Jiaming Zhu2
1School of Material Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, China.
Abstract:
Bacteria in tumor microenvironments promote carcinogenesis and trigger complications, suggesting the significance of intervening in bacterial growth in cancer treatment. Here, dendrimer-derived mimics (DMs) of host defense peptides (HDPs) were designed for antibacterial and anticancer therapy, which feature a dendronized polylysine core and polycaprolactone arms. DMs displayed not only remarkable activities against Staphylococcus aureus and human lung cancer cells, but also exceptional selectivity. The membranolytic mechanism revealed by morphology analysis explained their low susceptibility to induce resistance. Further, the optimized DM inhibited tumor growth in the subcutaneous tumor model when administered via intraperitoneal injection and exhibited negligible toxicity to tissues. Overall, we combined the superiority of dendrimers and the mechanism from HDPs to design agents with dual antibacterial and anticancer activities that possess great potential for clinical oncology therapy.
Insights
Dendrimer-derived mimics (DMs) show dual antibacterial and anticancer activity against Staphylococcus aureus and lung cancer cells. These agents effectively inhibited tumor growth with minimal toxicity, offering potential for clinical oncology.
Area of Science:
- Biomaterials Science
- Nanomedicine
- Cancer Therapy
Background:
- Tumor microenvironments harbor bacteria that promote cancer development and treatment complications.
- Host defense peptides (HDPs) offer a model for antimicrobial and anticancer strategies.
- Dendrimer-derived mimics (DMs) were designed to leverage HDP mechanisms for dual therapy.
Discussion:
- DMs demonstrated potent activity against Staphylococcus aureus and human lung cancer cells.
- Exceptional selectivity and a membranolytic mechanism suggest low resistance potential.
- Morphology analysis elucidated the interaction mechanism of DMs with bacterial and cancer cells.
Key Insights:
- Dendrimer-derived mimics (DMs) exhibit significant antibacterial and anticancer properties.
- The designed DMs show high selectivity, targeting cancer cells and bacteria effectively.
- A membranolytic mechanism contributes to the low susceptibility of DMs to induce resistance.
Outlook:
- Optimized DMs successfully inhibited tumor growth in vivo via intraperitoneal injection.
- The developed agents displayed negligible toxicity to host tissues.
- This research presents promising dual-action agents for clinical oncology, combining dendrimer advantages with HDP mechanisms.
