Multimodal nanoparticles that provide immunomodulation and intracellular drug delivery for infectious diseases

被引:61
作者
Dube, Admire [1 ]
Reynolds, Jessica L. [2 ]
Law, Wing-Cheung [3 ]
Maponga, Charles C. [1 ]
Prasad, Paras N. [3 ,4 ]
Morse, Gene D. [5 ]
机构
[1] Univ Zimbabwe, Sch Pharm, Harare, Zimbabwe
[2] SUNY Buffalo, Dept Med, Buffalo, NY 14203 USA
[3] SUNY Buffalo, Inst Lasers Photon & Biophoton, Buffalo, NY 14203 USA
[4] Korea Univ, Dept Chem, Seoul, South Korea
[5] SUNY Buffalo, New York State Ctr Excellence Bioinformat & Life, Sch Pharm & Pharmaceut Sci, Translat Pharmacol Res Core, Buffalo, NY 14203 USA
关键词
Infectious diseases; Multimodal nanoparticles; 1,3-beta-glucan; Mycobacterium tuberculosis; PLGA; MYCOBACTERIUM-TUBERCULOSIS; HUMAN MACROPHAGES; BETA-GLUCAN; IMMUNE; RECOGNITION; CYTOKINES;
D O I
10.1016/j.nano.2013.11.012
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Infectious diseases are a worldwide health concern. For some infections, a common feature is the intracellular residence of the pathogen and evasion of the host immune response. In the case of tuberculosis (TB), Mycobacterium tuberculosis evades clearance within macrophages through suppression of intracellular reactive oxygen and nitrogen species (ROS/RNS) and pro-inflammatory cytokines. We propose new nanoparticle designs for infectious diseases, functionalized with ligands able to modulate the cellular immune response and concurrently deliver drug. We have designed 1,3-beta-glucan functionalized chitosan shell, poly(lactide)co-glycolide core nanoparticles to stimulate ROS/RNS, pro-inflammatory cytokine secretion, and delivery of rifampicin inside human alveolar like macrophages (ALM). Nanoparticles significantly enhanced ALM secretion of IL-12p70 (2.9-fold), TNF-alpha (16-fold) and INF-gamma (23-fold) compared to controls over 24 h, and doubled ROS/RNS generation over 6 h. Nanoparticles could deliver 4-fold greater rifampicin into ALM compared to rifampicin solution. These results provide proof-of-concept of multimodal nanoparticles and support their further development. From the Clinical Editor: In this paper, a new nanoparticle design is proposed to address hard to treat infectious diseases such as TB, through the use of nanoparticles functionalized with ligands that are able to concurrently modulate the cellular immune response and deliver a drug. The authors have designed 1,3-beta-glucan functionalized chitosan shell - poly(lactide) co-glycolide core nanoparticles to stimulate reactive oxygen and nitrogen species production, pro-inflammatory cytokine secretion, and delivery of rifampicin inside human alveolar-like macrophages. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:831 / 838
页数:8
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