ABSTRACT
The NIR absorbing photosensitizer phthalocyanine zinc (PC(Zn)) was stabilized in aqueous media as water-dispersible nanoparticles with a reduction- and pH-responsive full polysaccharide block copolymer. A cellular uptake and also photo switchable intracellular activity of the cargo upon irradiation at wavelengths in the near infrared region were shown. The block copolymer was synthesized by applying a copper-free click strategy based on a thiol exchange reaction, creating an amphiphilic double-stimuli-responsive mixed disulfide. The dual-sensitive polysaccharide micelles represent a non-toxic and biodegradable green macrosurfactant for the delivery of phthalocyanine zinc. By encapsulation into micellar nanoparticles, the bioavailability of PC(Zn) increased significantly, enabling smart photodynamic therapy for future applications in cancer-related diseases.
Subject(s)
Dextrans/administration & dosage , Indoles/administration & dosage , Nanoparticles/administration & dosage , Organometallic Compounds/administration & dosage , Photosensitizing Agents/administration & dosage , Polysaccharides/administration & dosage , Surface-Active Agents/administration & dosage , Biological Availability , HeLa Cells , Humans , Isoindoles , Micelles , Photochemotherapy , Zinc CompoundsABSTRACT
A full polysaccharide amphiphilic block copolymer was prepared from end group-functionalized dextrans using copper-mediated azide-alkyne click chemistry. Sufficient modification of the reducing end in both blocks was achieved by microwave-enhanced reductive amination in a borate-buffer/methanol solvent system. The combination of a hydrophilic dextran block with a hydrophobic acetalated dextran block results in an amphiphilic structure that turns water-soluble upon acid treatment. The material has a low critical micelle concentration and self-assembles in water to spherical micellar nanoparticles. The formed nanoparticles have a narrow size distribution below 70 nm in diameter and disassemble in slightly acidic conditions. The amphiphilic polysaccharide system shows low toxicity and can stabilize the hydrophobic model drug curcumin in aqueous solutions over extended time periods.