Remotely Controllable Supramolecular Nanomedicine for Drug-Resistant Colorectal Cancer Therapy Caused by Fusobacterium nucleatum

© 2023 Wiley-VCH GmbH..

Fusobacterium nucleatum (Fn) existing in the community of colorectal cancer (CRC) promotes CRC progression and causes chemotherapy resistance. Despite great efforts that have been made to overcome Fn-induced chemotherapy resistance by co-delivering antibacterial agents and chemotherapeutic drugs, increasing the drug-loading capacity and enabling controlled release of drugs remain challenging. In this study, a novel supramolecular upconversion nanoparticle (SUNP) is constructed by incorporating a positively charged polymer (PAMAM-LA-CD) with Fn inhibition capacity, a negatively charged platinum (IV) oxaliplatin prodrug (OXA-COOH), upconversion nanoparticle (UCNPs) and polyethylene glycol-azobenzene (PEG-Azo) to enhance drug-loading and enable on-demand drug release for drug-resistant CRC treatment. SUNPs exhibit high drug-loading capacity (30.8%) and good structural stability under normal physiological conditions, while disassembled upon exogenous NIR excitation and endogenous azo reductase in the CRC microenvironment to trigger drug release. In vitro and in vivo studies demonstrate that SUNPs presented good biocompatibility and robust performance to overcome chemoresistance, thereby significantly inhibiting Fn-infected cancer cell proliferation. This study leverages multiple dynamic chemical designs to integrate both advantages of drug loading and release in a single system, which provides a promising candidate for precision therapy of bacterial-related drug-resistant cancers.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:8

Enthalten in:

Small methods - 8(2024), 3 vom: 22. März, Seite e2301309

Sprache:

Englisch

Beteiligte Personen:

Yan, Xiangjie [VerfasserIn]
Xin, Youtao [VerfasserIn]
Yu, Yunjian [VerfasserIn]
Li, Xiaohui [VerfasserIn]
Li, Boqiong [VerfasserIn]
Elsabahy, Mahmoud [VerfasserIn]
Zhang, Jimin [VerfasserIn]
Ma, Feihe [VerfasserIn]
Gao, Hui [VerfasserIn]

Links:

Volltext

Themen:

Colorectal cancer
Fusobacterium nucleatum
Journal Article
On-demand drug release
Supramolecular assembly
Upconversion nanoparticle

Anmerkungen:

Date Completed 21.03.2024

Date Revised 21.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1002/smtd.202301309

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM365095052