UC San Diego

Antibiotic resistance has become an undeniable burden on global health as we move further into the twenty-first century. It is predicted that drug-resistant infections could lead to an annual mortality rate of 10 million people by 2050 and a cumulative cost of up to 100 trillion USD on the world’s economy. These unsettling projections have necessitated the exploration of new and more effective ways to manage bacterial infection. This dissertation focuses on novel strategies for addressing this pressing challenge via nanomedicine, particularly the use of natural cell-derived membrane to enhance the biointerfacing of synthetic nanomaterials. The resulting membrane- cloaked platforms exhibit unique, cell-specific properties that can be leveraged for antibacterial therapy. Additionally, novel nano/micromotors are further exploited to design new biomimetic therapeutic modalities capable of active movement.

The first part of this thesis will focus on novel antibiotic delivery systems, including targeted delivery and active delivery platforms. For targeted antibiotic delivery, the native function of the source cells, particularly their natural adhesion property was exploit by the natural cell membranes-coated nanoparticles. Meanwhile, the second delivery platform involves mobile micromotor which are acid-powered and enable active delivery. Not only can the propulsion of antibiotic-loaded motors in gastric media effectively deliver the drug payload, but the motor-based therapy can also rapidly neutralize gastric acid without the need of proton pump inhibitor.

the second portion of this dissertation will focus on the exploitation of biomim- icking nanoplatforms as countermeasures against pathologic moieties for the abroga- tion of bacterial infection. This is demonstrated through a range of bacterial virulence including diarrhea-causing cholera toxin, Shiga toxin, and systemic endotoxin. Ul- timately, cell membrane-coated technology has the potential to greatly impact the landscape of nanomedicine and contribute to the management of bacterial infections in the future.