TY - JOUR
T1 - Receptor-mediated uptake of folic acid-functionalized dextran nanoparticles for applications in photodynamic therapy
AU - Butzbach, Kathrin
AU - Konhäuser, Matthias
AU - Fach, Matthias
AU - Bamberger, Denise N.
AU - Breitenbach, Benjamin
AU - Epe, Bernd
AU - Wich, Peter R.
PY - 2019
Y1 - 2019
N2 - In photodynamic therapy (PDT), photosensitizers and light are used to cause photochemically induced cell death. The selectivity and the effectiveness of the phototoxicity in cancer can be increased by a specific uptake of the photosensitizer into tumor cells. A promising target for this goal is the folic acid receptor α (FRα), which is overexpressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe a polysaccharide-based nanoparticle system suitable for targeted uptake and its photochemical and photobiological characterization. The photosensitizer 5, 10, 15, 20-tetraphenyl-21H, 23H-porphyrine (TPP) was encapsulated in spermine- and acetal-modified dextran (SpAcDex) nanoparticles and conjugated with folic acid (FA) on the surface [SpAcDex(TPP)-FA]. The particles are successfully taken up by human HeLa-KB cells, and a light-induced cytotoxicity is observable. An excess of free folate as the competitor for the FRα-mediated uptake inhibits the phototoxicity. In conclusion, folate-modified SpAcDex particles are a promising drug delivery system for a tumor cell targeted photodynamic therapy.
AB - In photodynamic therapy (PDT), photosensitizers and light are used to cause photochemically induced cell death. The selectivity and the effectiveness of the phototoxicity in cancer can be increased by a specific uptake of the photosensitizer into tumor cells. A promising target for this goal is the folic acid receptor α (FRα), which is overexpressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe a polysaccharide-based nanoparticle system suitable for targeted uptake and its photochemical and photobiological characterization. The photosensitizer 5, 10, 15, 20-tetraphenyl-21H, 23H-porphyrine (TPP) was encapsulated in spermine- and acetal-modified dextran (SpAcDex) nanoparticles and conjugated with folic acid (FA) on the surface [SpAcDex(TPP)-FA]. The particles are successfully taken up by human HeLa-KB cells, and a light-induced cytotoxicity is observable. An excess of free folate as the competitor for the FRα-mediated uptake inhibits the phototoxicity. In conclusion, folate-modified SpAcDex particles are a promising drug delivery system for a tumor cell targeted photodynamic therapy.
KW - Nanoparticles
KW - Dextran
KW - Targeting
KW - Folic acid
KW - Photodynamic therapy
U2 - 10.3390/polym11050896
DO - 10.3390/polym11050896
M3 - Journal article
C2 - 31100893
SN - 2073-4360
VL - 11
JO - Polymers
JF - Polymers
IS - 5
M1 - 896
ER -
