Inhalable Capsular Polysaccharide‐Camouflaged Gallium‐Polyphenol Nanoparticles Enhance Lung Cancer Chemotherapy by Depleting Local Lung Microbiota

Abstract

Local lung microbiota is closely associated with lung tumorigenesis and therapeutic response. It is found that lung commensal microbes induce chemoresistance in lung cancer by directly inactivating therapeutic drugs via biotransformation. Accordingly, an inhalable microbial capsular polysaccharide (CP)‐camouflaged gallium‐polyphenol metal–organic network (MON) is designed to eliminate lung microbiota and thereby abrogate microbe‐induced chemoresistance. As a substitute for iron uptake, Ga3+ released from MON acts as a “Trojan horse” to disrupt bacterial iron respiration, effectively inactivating multiple microbes. Moreover, CP cloaks endow MON with reduced immune clearance by masquerading as normal host‐tissue molecules, significantly increasing residence time in lung tissue for enhanced antimicrobial efficacy. In multiple lung cancer mice models, microbe‐induced drug degradation is remarkably inhibited when drugs are delivered by antimicrobial MON. Tumor growth is sufficiently suppressed and mouse survival is prolonged. The work develops a novel microbiota‐depleted nanostrategy to overcome chemoresistance in lung cancer by inhibiting local microbial inactivation of therapeutic drugs.

Recent progress in nanomaterials for bacteria-related tumor therapy

“…In order to inhibit chemotherapy resistance caused by commensal bacteria in lung tumors, Han et al 67 constructed an inhalable gallium-based metal nanoparticle coated with capsular polysaccharidecp (CP), defined as GaTa-cpNPs (Fig. 4a).…”

The emerging tumor microbe microenvironment: From delineation to multidisciplinary approach-based interventions

“…(G) Depletion of lung microbiota with bioinspired nanomedicine for improving lung cancer chemotherapy, reprinted with permission from Ref. 287 . Copyright © 2023 American Chemical Society.…”

Orally Administrated Hydrogel Harnessing Intratumoral Microbiome and Microbiota-Related Immune Responses for Potentiated Colorectal Cancer Treatment

“…Additionally, magnetic natural lipid NPs have been used for oral treatment of colorectal cancer, potentiating antitumor immunity and regulating microbiota metabolites [ 17 ]. Inhalable capsular polysaccharide-camouflaged gallium-polyphenol NPs have been shown to enhance lung cancer chemotherapy by depleting local lung microbiota [ 18 ]. Furthermore, fecal microbiota transplantation has been found to improve the efficacy of tirilizumab and furaquintinib in colorectal cancer by remodeling the microbial environment [ 19 ].…”