(351b) Quantification of Intracellular Distribution of Agents by pH-Responsive Blend Polymer Particles

The ability to deliver biological agents into defined intracellular compartments offers a promising strategy for targeting multiple signaling pathways in cells. In this study, pH-responsive polymer particles made from a blend of multiple polymers, poly(lactic-co-glycolic acid) (PLGA) and random pH-sensitive copolymer, have been developed for the intracellular delivery of agents. The polymeric blend particles exhibited different pH sensitivity and conformation depending on the ratios of two polymers. These blend particles were able to induce endosomal/lysosomal leakage in antigen-presenting cells (APCs). Multiple methods were used to quantify the intracellular distribution of cargos with varying sizes in APCs. The results showed that the distribution of agents in two intracellular compartments, lysosomes and cytosol, depended on the composition of the copolymer, the ratio of copolymer in blend particles as well as the size of cargos. This study presents a mechanistic understanding of routing agents into different intracellular compartments by pH-responsive carriers for intracellular delivery.