A dendritic polyamidoamine supramolecular system composed of pillar[5]arene and azobenzene for targeting drug-resistant colon cancer.

Abstract

Fusobacterium nucleatum caused drug-resistant around tumor sites often leads to the failure of chemotherapy during colorectal cancer (CRC) treatment. Multifunctional cationic quaternary ammonium materials have been widely used as broad-spectrum antibacterial agents in antibacterial and anticancer fields. Herein, we design a smart supramolecular quaternary ammonium nanoparticle, namely quaternary ammonium PAMAM-AZO@CP[5]A (Q-P-A@CP[5]A), consisting of azobenzene (AZO)-conjugated dendritic cationic quaternary ammonium polyamidoamine (PAMAM) as the core and carboxylatopillar[5]arene (CP[5]A)-based switch, for antibacterial and anti-CRC therapies. The quaternary ammonium-PAMAM-AZO (Q-P-A) core endows the supramolecular system with enhanced antibacterial and anticancer properties. -N+CH3 groups on the surface of Q-P-A are accommodated in the CP[5]A cavity under normal conditions, which significantly improves the biocompatibility of Q-P-A@CP[5]A. Meanwhile, the CP[5]A host can be detached from -N+CH3 groups under pathological conditions, achieving efficient antibacterial and antitumor therapies. Furthermore, azoreductase in the tumor site can break the -NN- bonds of AZO in Q-P-A@CP[5]A, leading to the morphology recovery of supramolecular nanoparticles and CRC therapy through inducing cell membrane rupture. Both in vitro and in vivo experiments demonstrate that Q-P-A@CP[5]A possesses good biocompatibility, excellent antibacterial effect, and CRC treatment capability with negligible side effects. This supramolecular quaternary ammonium system provides an effective treatment method to overcome chemotherapy-resistant cancer caused by bacteria.

• Authors: Hongyu Liu, Jie Yang, Xiangjie Yan, Chaoqi Li, Mahmoud Elsabahy, Li Chen, Ying-Wei Yang, Hui Gao
• Journal: Journal of materials chemistry. B (J Mater Chem B) Vol. 9 Issue 46 Pg. 9594-9605 (12 01 2021) ISSN: 2050-7518 [Electronic] England
• PMID: 34783814 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Antifungal Agents
• Antineoplastic Agents
• Azo Compounds
• Poly(amidoamine)
• Polyamines
• Quaternary Ammonium Compounds
• carboxylatopillar(5)arene
• azobenzene

Topics

• Animals
• Anti-Bacterial Agents
• Antifungal Agents
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis
• Azo Compounds (chemistry)
• Cell Survival
• Drug Design
• Drug Resistance, Fungal
• Drug Resistance, Neoplasm
• Fusobacterium nucleatum (drug effects)
• HT29 Cells
• Humans
• Male
• Mice
• Mice, Nude
• Models, Molecular
• Molecular Structure
• Nanoparticles (chemistry)
• Neoplasms, Experimental
• Polyamines (chemistry)
• Quaternary Ammonium Compounds (chemistry)
• Xenograft Model Antitumor Assays