Tumor-Targeting Nanoassembly for Enhanced Colorectal Cancer Therapy by Eliminating Intratumoral Fusobacterium nucleatum.

Abstract

Fusobacterium nucleatum (Fn) has long been found to be related to colorectal cancer (CRC), which could promote colorectal tumor progression and cause cancer resistance to chemotherapy. Great efforts have been made to understand the relationship between Fn and CRC, but how to efficiently eliminate intratumoral Fn and overcome chemoresistance remains a critical challenge. Here, an active tumor-targeting acidity-responsive nanomaterial toward eliminating intratumoral Fn is developed for enhancing the treatment of cancer. Lauric acid and phenylboric acid are conjugated to oligomethyleneimine to form OLP followed by interacting with oxaliplatin prodrug-modified polyglycidyl ether (PP) to obtain the OLP/PP nanoassembly. The nanoassembly shows good structural stability under the simulated physiological conditions and has a pH-responsive drug release in an acidic tumor microenvironment. More attractively, the nanoassembly can specifically target the tumor cell, guide cellular uptake, and efficiently eliminate tumor-resident extracellular and intracellular Fn. Through the on-site drug delivery, the nanoassembly can overcome chemoresistance and significantly inhibit tumor growth. Both in vitro and vivo studies show that the prepared nanoassembly presents good biocompatibility. Therefore, this biocompatible nanoassembly possessing efficient antibacterial and antitumor activities provides new promise for the therapy of bacterial infected tumors.