AniView Supports Targeted Phototherapy Research: NIR-II AIE Luminogen-Based Erythrocyte-Like Nanoparticles with Granuloma-Targeting and Self-Oxygenation Characteristics for Combined Phototherapy of Tu

New progress has been made in granuloma-targeted combination phototherapy for tuberculosis using NIR-II AIE luminogen-based erythrocyte-like nanoparticles with self-oxygenation capabilities.

Yuhui Liao from Kunming Medical University and Ningxia Medical University, in collaboration with Xiaoming Zou from Southern Medical University, Dong Wang from Shenzhen University, and Dingyuan Yan, has made new progress in developing biomimetic nanoparticles for fluorescence imaging-guided targeted combination phototherapy for tuberculosis. Their findings have been published in the international authoritative journal “Advanced Materials” (IF = 26.8, Q1 journal).

This study provides a novel therapeutic strategy for tuberculosis by integrating granuloma targeting, self-oxygenation, and combined photodynamic and photothermal therapy into a multifunctional biomimetic nanoplatform, overcoming the hypoxic microenvironment of granulomas and improving therapeutic efficacy.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is an infectious disease with high incidence and mortality worldwide. Current clinical treatment relies on antibiotics, but faces challenges including drug resistance, short drug half-lives, and significant side effects. Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), offers a non-invasive alternative that is less likely to induce drug resistance. However, its therapeutic efficacy is limited by the hypoxic microenvironment of granulomas, one of the hallmarks of tuberculosis, which hinders the generation of reactive oxygen species (ROS) during PDT, as well as insufficient targeting capability.

In existing studies, aggregation-induced emission (AIE) photosensitizers exhibit enhanced fluorescence and ROS generation in the aggregated state, making them suitable for imaging-guided PDT. Perfluorocarbons (PFCs) can efficiently carry oxygen to alleviate hypoxia; Prussian blue (PB) nanoparticles possess both photothermal effects and drug-loading capabilities; and red blood cell (RBC) membrane coating can prolong nanoparticle circulation in the bloodstream and enhance targeting. However, an integrated nanoplatform combining these properties to achieve granuloma targeting, self-oxygenation, and combination phototherapy has not yet been developed, presenting a key challenge in tuberculosis treatment.

Therefore, the research team developed a multifunctional nanoparticle disguised with an RBC membrane (RBC-O₂/TQ@PB), integrating an AIE photosensitizer (PEG₂₅₀-TQ), PFC for oxygen delivery, and PB as a photothermal agent. This platform enables granuloma targeting, self-oxygenation, and combined PDT and PTT.

The nanoparticles prolong blood circulation through the CD47 protein on the RBC membrane and accumulate in granulomas via the enhanced permeability and retention (EPR) effect. PFC releases oxygen to alleviate hypoxia, promoting the generation of more ROS by the AIE photosensitizer under laser irradiation and thereby enhancing PDT. PB generates a photothermal effect under laser irradiation to achieve PTT, while the increased blood flow induced by photothermal effects further improves oxygen supply. In vitro and in vivo experiments demonstrated that the nanoparticles effectively inhibited the proliferation of Mycobacterium tuberculosis and its surrogate strains, M. marinum (M.m) and BCG, reduced granulomatous lesions, and exhibited good biocompatibility, with a hemolysis rate of less than 5%, low cytotoxicity toward normal cells, and no damage to major organs.

This self-oxygenating biomimetic nanoplatform is the first to achieve efficient anti-tuberculosis treatment by alleviating granuloma hypoxia to enhance AIE photosensitizer-mediated PDT in combination with PTT, providing a new paradigm for the clinical treatment of tuberculosis.

Experiments using Aniview

In this study, the research team used the AniView multimodal in vivo imaging system from Guangzhou Biolight Biotechnology Co., Ltd. to investigate the granuloma-targeting capability and retention of RBC-O₂/TQ@PB nanoparticles. The results in Figure d show that, in a mouse tail granuloma model induced by M.m, RBC-O₂/TQ@PB nanoparticles accumulated to a greater extent in tail granulomas than O₂/TQ@PB nanoparticles at the same time points. Their accumulation reached its maximum at 24 h, and they remained in the granulomas even at 48 h. These findings indicate that RBC-O₂/TQ@PB nanoparticles possess stronger granuloma-targeting capability and longer retention times, which is beneficial for tuberculosis treatment.

The results in Figure f show that, in a mouse model of pulmonary tuberculosis induced by BCG, both types of nanoparticles were primarily distributed in the liver, kidneys, and lungs. However, compared with O₂/TQ@PB nanoparticles, RBC-O₂/TQ@PB nanoparticles exhibited reduced uptake by the reticuloendothelial system, including the liver, while increasing retention and targeting in pulmonary granulomas. This helps improve their therapeutic efficacy against tuberculosis in vivo.

DOI： 10.1002/adma.202406143