In:
Advanced Materials, Wiley, Vol. 34, No. 12 ( 2022-03)
Abstract:
Intracellular bacteria in latent or dormant states tolerate high‐dose antibiotics. Fighting against these opportunistic bacteria has been a long‐standing challenge. Herein, the design of a cascade‐targeting drug delivery system (DDS) that can sequentially target macrophages and intracellular bacteria, exhibiting on‐site drug delivery, is reported. The DDS is fabricated by encapsulating rifampicin (Rif) into mannose‐decorated poly(α‐ N ‐acryloyl‐phenylalanine)‐ block ‐poly(β‐ N ‐acryloyl‐ d ‐aminoalanine) nanoparticles, denoted as Rif@FAM NPs. The mannose units on Rif@FAM NPs guide the initial macrophage‐specific uptake and intracellular accumulation. After the uptake, the detachment of mannose in acidic phagolysosome via Schiff base cleavage exposes the d ‐aminoalanine moieties, which subsequently steer the NPs to escape from lysosomes and target intracellular bacteria through peptidoglycan‐specific binding, as evidenced by the in situ/ex situ co‐localization using confocal, flow cytometry, and transmission electron microscopy. Through the on‐site Rif delivery, Rif@FAM NPs show superior in vitro and in vivo elimination efficiency than the control groups of free Rif or the DDSs lacking the macrophages‐ or bacteria‐targeting moieties. Furthermore, Rif@FAM NPs remodel the innate immune response of the infected macrophages by upregulating M1/M2 polarization, resulting in a reinforced antibacterial capacity. Therefore, this biocompatible DDS enabling macrophages and bacteria targeting in a cascade manner provides a new outlook for the therapy of intracellular pathogen infection.
Type of Medium:
Online Resource
ISSN:
0935-9648
,
1521-4095
DOI:
10.1002/adma.202109789
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
1474949-X
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