Spectroscopic investigation of a hyperbranched cationic amylopectin derivative as a multi-guest molecular host for targeted delivery of a photosensitizer to pancreatic cancer cells

Abstract

To increase pancreatic tumor-targeted phototoxicity of photosensitizers, a hyperbranched cationic amylopectin derivative conjugated with 3-(dimethylamino)-1-propylamine (DMAPA-Amp) was invevstigated as a multi-guest molecular host for the targeted delivery of a photosensitizer to human pancreatic cancer (Panc-1) cells. We selected protoporphyrin IX (PpIX) and folic acid as a photosensitizer and a tumor-targeting factor, respectively. The complexation mechanism of DMAPA-Amp with PpIX and folic acid was characterized using NMR spectroscopy including ¹H NMR, two-dimensional diffusion ordered spectroscopy (2D DOSY) NMR, fluorescence and UV-vis spectroscopy. The results indicated that the DMAPA-Amp derivative could serve as a host for the encapsulation of two guests, PpIX and folic acid, through intermolecular interactions. The complex showed high phototoxicity against Panc-1 cells, and its folic-acid-mediated cancer-cell-targeting property was confirmed by laser confocal microscopy and flow cytometry analysis. We provide a method to study hyperbranched cationic polymer-based complexes containing multiple guests, which could facilitate the design of multi-functional complexes in the drug delivery field.

Keywords: Amylopectin; Complexation mechanism; Fluorescence spectroscopy; NMR spectroscopy; Photosensitizer.