Photothermal and host immune activated therapy of cutaneous tuberculosis using macrophage targeted mesoporous polydopamine nanoparticles

  • Mater Today Bio. 2024 Sep 10:28:101232. doi: 10.1016/j.mtbio.2024.101232.
Shuhao Fan  1  2 ,  Daina Zhao  1  2 ,  Jiajun Wang  1  2 ,  Yuhe Ma  1  2 ,  Dongsheng Chen  1  2 ,  Yuhe Huang  1  2 ,  Tangxin Zhang  1  2 ,  Yilin Liu  1  2 ,  Jiaojiao Xia  3 ,  Xueqin Huang  1  2 ,  Yujia Lu  2 ,  Yongdui Ruan  1 ,  Jun-Fa Xu  1  2 ,  Ling Shen  4 ,  Fen Yang  1  2 ,  Jiang Pi  1  2
Affiliations
  • 1. Research Center of Nano Technology and Application Engineering, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, China.
  • 2. Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, Guangdong Medical University, Dongguan, China.
  • 3. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, China.
  • 4. Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, USA.
PMID: 39315396 DOI: 10.1016/j.mtbio.2024.101232
Abstract

Tuberculosis (TB) remains the leading cause of deaths among infectious diseases worldwide. Cutaneous Tuberculosis (CTB), caused by Mycobacterium tuberculosis (Mtb) Infection in the skin, is still a harmful public health issue that requires more effective treatment strategy. Herein, we introduced mannose-modified mesoporous polydopamine nanosystems (Man-mPDA NPs) as the macrophage-targeted vectors to deliver anti-TB drug rifampicin and as photothermal agent to facilitate photothermal therapy (PTT) against Mtb infected macrophages for synergistic treatment of CTB. Based on the selective macrophage targeting effects, the proposed Rif@Man-mPDA NPs also showed excellent photothermal properties to develop Rif@Man-mPDA NPs-mediated PTT for intracellular Mtb killings in macrophages. Importantly, Rif@Man-mPDA NPs could inhibit the immune escape of Mtb by effectively chelating intracellular Fe2+ and inhibiting lipid peroxidation, and up-regulating GPX4 expression to inhibit Ferroptosis of Mtb infected macrophages through activating Nrf2/HO-1 signaling. Moreover, Rif@Man-mPDA NPs-mediated PTT could effectively activate host cell immune responses by promoting Autophagy of Mtb infected macrophages, which thus synergizes targeted drug delivery and Ferroptosis inhibition for more effective intracellular Mtb clearance. This Rif@Man-mPDA NPs-mediated PTT strategy could also effectively inhibit the Mtb burdens and alleviate the pathological lesions induced by Mtb Infection without significant systemic side effects in mouse CTB model. These results indicate that Rif@Man-mPDA NPs-mediated PTT can be served as a novel anti-TB strategy against CTB by synergizing macrophage targeted photothermal therapy and host immune defenses, thus holding promise for more effective treatment strategy development against CTB.

Keywords
Autophagy; Cutaneous tuberculosis; Ferroptosis; Host directed therapy; Macrophages; Photothermal therapy.
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