Engineering nanoparticles to tackle tumor barriers

Engineering strategies of nanoparticles were elaborated to overcome delivery barriers from the perspectives of trans-vascular transport and interstitial transport.

Effect of Assembly Method on Nanoparticle Attachment Density, Growth Rate, and Motility of Nanoscale Bacteria Enabled Autonomous Drug Delivery System (NanoBEADS)

Microbial-mediated drug delivery systems have the potential to significantly enhance the efficacy of nanomedicine for cancer therapy through improved specificity and interstitial transport. The Nanoscale Bacteria-Enabled Autonomous Drug Delivery System (NanoBEADS) is a bacteria-based bio-hybrid drug delivery system designed to carry nanotherapeutics cargo deep into poorly vascularized cancerous tissue. The effect of bacteria-nanoparticle conjugation method and NanoBEADS assembly parameters (i.e., mixing method, volume, and duration) was investigated to maximize particle attachment density. The nanoparticle attachment capacity, viability, growth rate and motility of the original NanoBEADS and an antibody-free variant NanoBEADS were characterized and compared. It is found that the assembly parameters affect the attachment outcome and the binding mechanism impacts the attachment number, the growth rate and motility of NanoBEADS. The NanoBEADS platform provides an opportunity to load nanoparticles with different materials and sizes for applications beyond cancer therapy, such as imaging agents for high-resolution medical imaging.

Micro-Pharmacodynamics: Bridging In Vitro and In Vivo Experimental Scales in Testing Drug Efficacy and Resistance

Systemic chemotherapy is one of the main anticancer treatments used for most kinds of clinically diagnosed tumors. However, the efficacy of these drugs can be hampered by the physical attributes of the tumor tissue that can impede the transport of therapeutic agents to tumor cells in sufficient quantities. As a result, drugs that work well in vitro often fail at clinical trials when confronted with the complexities of interstitial transport within the tumor microenvironment. The microPD model that we developed is used to investigate the penetration of drug molecules through the tumor tissue and influenced by the physical and metabolic properties of tumor microenvironment, and how it affects drug efficacy and the emergence of drug resistance.