Apoptotic body-encapsulated nanoparticles regulate inflammation through macrophage polarization mediated by lactic acid

Background: Inflammation has been implicated in numerous diseases. The treatment of inflammation-related diseases is a significant global burden. Recent studies have found that lactic acid and its signalling pathway can inhibit inflammatory responses through macrophage polarization without any toxic side effects.

Objective: This study aimed to develop a rational drug delivery system that can release lactic acid into the desired area.

Methods: We extracted the macrophage-derived apoptotic bodies (ABs) to prepare the AB-encapsulated nanoparticles (ABNs) and evaluated the amount of lactic acid released and the safety of ABNs. Then, we observed the anti-inflammatory effect of ABNs and the phenotypic distribution of macrophages in vitro and in vivo.

Results: ABNs were specifically taken up by activated macrophages in vitro and in vivo. The levels of Reactive Oxygen Species and inflammatory signalling proteins significantly decreased in activated macrophages after ABN treatment. ABNs relieved the inflammation of the colon and liver tissue, reduced the expression of TNF-α and IL-1β in serum, and inhibited the expression of TLR4/NF-κB proteins. The immunofluorescence images revealed that ABNs promoted the transformation of M1 macrophages (CD86+) into the M2 phenotype (CD206+). The expression of CD86 and iNOS decreased, whereas the expression of CD206 and Arg-1 significantly increased in the ABN-treated group. The cytotoxicity test revealed no obvious cytotoxic effect of ABNs.

Conclusions: ABNs can regulate the phenotypic transformation of macrophages through the local release of lactic acid and improve inflammation and injury of the liver and colon in mice. Our study demonstrated that the proposed nanosystem could serve as a promising delivery platform for the release of lactic acid to effectively reduce inflammation.