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Cationic Polypeptide Dendrimers with Concurrent Antibacterial and Anticancer Activities Depending on Topological
Yusheng Qian1, Xiangyu Lin2, Shuting Huang1
1School of Material Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, China.
Biomacromolecules
|November 20, 2025
Summary
New polypeptide dendrimers show dual antibacterial and anticancer effects. The best candidate, LysG5, effectively reduced tumor growth in vivo with minimal damage to healthy tissues.
Area of Science:
- Biochemistry
- Materials Science
- Oncology
Background:
- Bacterial infections impede cancer treatment, requiring agents with combined antibacterial and anticancer properties.
- Designing host defense peptide (HDP) mimics with dual efficacy through membrane lysis is challenging.
Purpose of the Study:
- To construct and evaluate cationic polypeptide dendrimers as HDP mimics for concurrent antibacterial and anticancer therapy.
- To investigate the impact of dendrimer generation and interior size on efficacy and mechanism.
Main Methods:
- Synthesis of two series of cationic polypeptide dendrimers (OrnGn and LysGn, n=3-5).
- Assessment of antimicrobial and antitumor activities (MIC, IC50).
- Analysis of membrane morphology and in vivo tumor suppression.
Main Results:
- Efficacy was dependent on dendrimer generation and interior size.
- LysG5 showed potent antitumor (IC50 = 64 μg/mL) and antibacterial (MIC = 16 μg/mL) activity.
- Increased generation enhanced membranolytic domains; larger interior size improved membrane penetration.
- LysG5 significantly reduced tumor weight in vivo (64%, p < 0.001) with no significant damage to healthy tissues.
Conclusions:
- Optimizing dendrimer topology is a promising strategy for developing HDP mimics with dual antibacterial and anticancer functions.
- Cationic polypeptide dendrimers offer a potential solution for treating complex bacterial and tumor co-infections.
