Palmitic acid-capped MIL-101-Al as a nano-adjuvant to amplify immune responses against

• Published in: Nanoscale 2024-05, Vol.16 (21), p.136-1317
• Main Authors: Chen, Lingming, Liu, Shuai, Zhang, Yunting, Tang, Qiling, Quan, Chunyu, Wang, Jundan, Peng, Xinsheng, Zhong, Xiaofang
• Format: Article
• ISSN: 2040-3364; 2040-3372
• DOI: 10.1039/d4nr01180e

As a highly contagious opportunistic pathogen, Pseudomonas aeruginosa ( P . aeruginosa ) is one of the main causes of healthcare-associated infections. The drug-resistant nature of P . aeruginosa can render antibiotic treatments ineffective, leading to a high morbidity and mortality. Higher specificity and reduced toxicity are features of immunotherapy, which can generate robust immune responses and preserve long-term immunological memory to completely eradicate infections. In this study, we developed a type of P. aeruginosa vaccine based on a metal-organic framework. Specifically, MIL-101-Al nanoparticles were synthesized to encapsulate antigens derived from the bacterial lysate (BL) of PAO1, a drug-resistant P . aeruginosa , and the adjuvant unmethylated cytosine-phosphate-guanine oligonucleotide (CpG), which were then modified with palmitic acid (PAA) to obtain MIL-BC@PAA. The stability and biocompatibility were significantly increased by capping with PAA. Moreover, MIL-BC@PAA showed significantly enhanced uptake by antigen presenting cells (APCs), and promoted their maturation. Importantly, immunity studies revealed the greatly elicited antigen-specific humoral and cellular responses, and a protection rate of about 70% was observed in P . aeruginosa -challenged mice. Overall, these results demonstrate the promising potential of MIL-BC@PAA as an ideal nanovaccine for P . aeruginosa vaccination. MIL-BC@PAA accumulated in lymph nodes and was internalized by DCs after subcutaneous injection, then induced DC maturation and finally elicited potent humoral and cellular immune responses for eliminating pathogens.