Inhalable nanoaerosols target the activation of HSP70 to regulate macrophage reprogramming for the treatment of bacterial pneumonia
image: Under NIR irradiation, MPDA/B@M’s photothermal effect directly eradicates pathogens while upregulating HSP70 to enhance host inflammation tolerance. This synergizes with bufalin’s anti-inflammatory activity to remodel the immune microenvironment, reprogramming macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotypes. Ultimately achieving the goal of treating bacterial pneumonia.
Credit: Nano Research, Tsinghua University Press
Bacterial pneumonia poses a major global public health threat. Among bacterial pneumonias, methicillin-resistant Staphylococcus aureus (MRSA) pneumonia presents particular clinical challenges due to multidrug resistance and complex pathological mechanisms. Addressing the challenging issue of the vicious cycle of infection inflammation injury in the treatment of MRSA pneumonia. Xin Ding, Yan-Jun Hu et al. designed a glycosylated mesoporous polydopamine nanoaerosol (MPDA/B@M), which achieved effective treatment of MRSA infected pneumonia through multi mechanism synergistic effects.
Addressing the challenging issue of the vicious cycle of infection inflammation injury in the treatment of MRSA pneumonia. Professor Yan-Jun Hu’s team from Hubei Normal University have designed a glycosylated mesoporous polydopamine nanoaerosols (MPDA/B@M), which achieves effective treatment of MRSA infected pneumonia through multi mechanism synergistic effects. The aerosol encapsulates bufalin, an active component of traditional Chinese medicine, within MPDA carriers. Surface modification with mannose enables macrophage-targeted delivery. Upon inhalation, the aerosol accumulates efficiently in pulmonary lesions, directly killing pathogens via photothermal effects while releasing bufalin to suppress inflammation. The synergistic “targeted delivery-photothermal intervention-immunomodulation” mechanism establishes MPDA/B@M as an efficient, precise, and safe therapeutic paradigm for drug-resistant pneumonia with significant clinical translatability.
The team published their study in Nano Research on December 23, 2025.
“We have successfully designed a glycosylated multifunctional nano aerosol MPDA/B@M, which integrates targeted delivery, photothermal antibacterial activity, ROS clearance, and HSP70 mediated macrophage reprogramming. This multimodal strategy can effectively break the vicious cycle of infection, inflammation, and injury in the treatment of drug-resistant bacterial pneumonia,” said Yan-Jun Hu, senior author of the study paper, professor at the College of Chemistry and Chemical Engineering, Hubei Normal University.
Bufalin, as the core active substance of traditional Chinese medicine Bufalin, can intervene in the infection process through multiple mechanisms: on the one hand, it can inhibit the growth of Staphylococcus aureus, and on the other hand, it can downregulate pro-inflammatory factors to achieve anti-inflammatory effects.
The research team not only improved the bioavailability of traditional Chinese medicine by loading it, but also further enhanced its therapeutic effect through photothermal therapy. “In traditional Chinese medicine, we have found that Chandu Ling has certain antibacterial and anti-inflammatory characteristics. By modifying it and combining it with mild photothermal therapy, we can enhance its synergistic effect. Through targeted delivery, photothermal intervention, and immune regulation, we can achieve a good therapeutic effect on bacterial pneumonia,” Yan-Jun Hu said.
Inhalation therapy is a relatively mild treatment method that causes minimal damage to the body. Yan-Jun Hu said, “In vivo studies confirmed preferential lung lesion accumulation following aerosol delivery, significantly reducing bacterial loads, reversing histopathological damage, and showing no systemic toxicity. And in the future treatment of pneumonia, the use of nebulized inhalation therapy may become increasingly widespread.”
In today's rapidly advancing technology, there are many highly effective treatment methods for combating bacterial infections. However, while these methods produce significant therapeutic effects, they also bring some side effects that cannot be ignored. Yan-Jun Hu said, “Our goal is to use a series of mild treatment methods to coordinate our own immune response and jointly fight against bacterial infections. Ensure minimal side effects on the body while effectively treating bacterial infections. We believe that this will be the major trend in nanomedicine therapy in the future, and also meet people's increasing pursuit of health.”
Other contributors include Hu Miao, Xin Ding, Shuang Cai, Ze-Wei Feng, Xin Li and Xiao-Huan Huang from the Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, College of Chemistry and Chemical Engineering, Hubei Normal University in Huangshi, China; and Qi-Ying Yu from the Central laboratory, Tumor Hospital Affiliated to Nantong University in Nantong, China.
This work was supported by the National Natural Science Foundation of China (No. 22173029), the Natural Science Foundation of Nantong Municipal Science and Technology Bureau (JC2024011), Excellent Young and Middle-aged Science and Technology Innovation Team Program of Universities in Hubei Province (Grant No. T2024014), the Talent Introduction Project of Hubei Normal University (HS2023RC078) and the Open Research Fund of Hubei Key Laboratory of Pollutant Analysis & Reuse Technology (PA230213).
DOI Link:
https://doi.org/10.26599/NR.2025.94908286
About Nano Research
Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 8,000 articles. In 2025 InCites Journal Citation Reports, its 2025 IF is 9.4 (8.3, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.