Abstract
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.
Highlights
Targeted drug delivery to tumors using nanoparticles (NPs) is an emerging area in cancer nanomedicine
We reduced the cost and conjugated folic acid to alginate in a simple way to increase the 5-aminolevulinic acid (5ALA) encapsulation ratio and devised a drug delivery system that could be used in vivo later
To allow sodium alginate to be dissolved in an organic solvent, it was modified with tetrabutylammonium hydroxide solution (TBAOH) [29,30]
Summary
Targeted drug delivery to tumors using nanoparticles (NPs) is an emerging area in cancer nanomedicine. Studies are needed to improve drug selectivity, prolong blood circulation, and reduce the side effects of therapeutic NPs [1,2]. Numerous types of NPs have been developed over the years, which are widely utilized in bioimaging due to their optimized surface modification and the ability to transport various therapeutic components [4]. Over the past few decades, fluorescence-mediated cancer detection has evolved to accurately differentiate cancer tissues, rather than distinguishing cancer tissues based on subjective evaluation with the naked eye [9]. These advances reduce the time and cost of cancer treatment and improve quality. Despite practical research efforts, biological barriers to the transport of fluorescent materials, such as enzymatic degradation, inadequate accumulation, and nonspecific distribution still remain to be crossed [1,3]
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