pH-Sensitive Folic Acid Conjugated Alginate Nanoparticle for Induction of Cancer-Specific Fluorescence Imaging.

In cancer nanomedicine, numerous studies have been conducted on the surface modification and transport capacity of nanoparticles (NPs); however, biological barriers, such as enzymatic degradation or non-specific delivery during circulation, remain to be cleared. Herein, we developed pH-sensitive NPs that degrade in an acidic environment and release 5-aminolevulinic acid (5ALA) to the target site. NPs were prepared by conjugating alginate with folic acid, followed by encapsulation of 5ALA through a water-in-oil (W/O) emulsion method. The alginate-conjugated folic acid nanoparticles (AF NPs) were homogeneous in size, stable for a long time in aqueous suspension without aggregation, and non-toxic. AF NPs were small enough to efficiently infiltrate tumors (<50 nm) and were specifically internalized by cancer cells through receptor-mediated endocytosis. After the intracellular absorption of NPs, alginate was deprotonated in the lysosomes and released 5ALA, which was converted to protoporphyrin IX (PpIX) through mitochondrial heme synthesis. Our study outcomes demonstrated that AF NPs were not degraded by enzymes or other external factors before reaching cancer cells, and fluorescent precursors were specifically and accurately delivered to cancer cells to generate fluorescence.