Protein corona mediated liposomal drug delivery for bacterial infection management

Liposomes have been widely investigated as a class of promising antibiotic delivery systems for the treatment of life-threatening bacterial infections.However,the inevitable formation of protein corona on the liposomal surface can heavily impact in vivo performance.A better understanding of the effects of protein corona on liposomal behavior can significantly improve antibacterial liposomal drug development.Here,the critical role of protein corona in mediating liposome-bacteria interactions was elucidated.Adsorption of negatively charged protein on cationic liposome weakened electrostatic attractionenhanced liposomal binding to the bacteria.Cumulative complement deposition on anionic liposome composed of phosphatidylglycerol(DSPG s Lip)contributed to a superior binding affinity of DSPG s Lip to planktonic bacteria and biofilms,which was exploited to enhance bacteria-targeted drug delivery.In both S.aureus-related osteomyelitis and pneumonia mice models,DSPG s Lip was demonstrated as a promising antibiotic nanocarrier for managing MRSA infection,indicating the benefits of lipid composition-based protein corona modulation in liposomal antibiotic delivery for bacterial infection treatment.

mIgM-mediated splenic marginal zone B cells targeting of folic acid for immunological evasion

Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities.Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B(MZB)cells.Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M(IgM),targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor(BCR)complex and block immune responses.The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens.Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies,which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions.Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies,and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.

Exemplifying interspecies variation of liposome in vivo fate by the effects of anti-PEG antibodies

The different fate of liposomes among species has been discovered and mentioned in many studies, but the underlying mechanisms have not been explored. In the present work, we concentrated on the in vivo fate of PEGylated liposomes (sLip) in three commonly used species (mice, rats, and dogs). It was exhibited that the accelerated blood clearance (ABC) phenomenon and hypersensitivity in large animals (beagle dogs) were much more significant than that in rodents. We demonstrated that anti-PEG IgM (partially) and complement (mostly) determined the elimination of sLip and linked the distinct interspecies performances with the diverse complement capacity among species. Based on the data from animals and clinical patients, it was revealed that the fate of sLip in large animals was closer to that in humans, for the sufficient complement capacity could expose the potential adverse reactions caused by anti-PEG antibodies. Our results suggested that the distinctive interspecies performances of sLip were highly related to the physiological variabilities among species, which should not be overlooked in the innovation and translation of nanomedicines.