Development of a Novel Covalent Folate-Albumin-Photosensitizer Conjugate.

There is considerable interest in the development of novel and more efficient delivery systems for improving the efficacy of photodynamic therapy (PDT). The authors in this highlighted issue describe the synthesis and the photobiological characterizations of two photosensitizer (PS) conjugates based on β-carboline derivatives covalently conjugated to folic acid (FA) coupled to bovine serum albumin (BSA) as a carrier system specifically targeting cancer cells overexpressing FA receptor alpha (FRα). Accordingly, only the FA-BSA-β-carboline conjugates are internalized specifically in FRα-positive cells and are proved to be phototoxic. On the other hand, albumin-β-carboline conjugates without FA or β-carboline derivatives alone are not internalized and nontoxic. This conjugate is among the first to produce a conjugate composed of a PS and FA molecules that are directly conjugated to BSA. In addition, the in vitro studies are the first evidence that directly conjugated FA-BSA can be used as carriers to selectively enhance cytotoxicity by PDT relative to unmodified PS or nontargeted BSA-PS. This strategy is a positive step forward for the covalent design and construction of a photodynamic nanomedicine for FR-positive tumors.