title: Polyacrylamide nanoparticles as a delivery system in photodynamic therapy.
abstract: Nanoparticles can be targeted towards, and accumulate in, tumor tissue by the enhanced permeability and retention effect, if sequestration by the reticuloendothelial system (RES) is avoided. The application of nanoparticles in the field of drug delivery is thus an area of great interest, due to their potential for delivering high payloads of drugs site selectively. One area which may prove to be particularly attractive is photodynamic therapy, as the reactive oxygen species (ROS) which cause damage to the tumor tissue are not generated until the drug is activated with light, minimizing generalized toxicity and giving a high degree of spatial control over the clinical effect. In the present study, we have synthesized two types of nanoparticles loaded with photodynamic sensitizers: polylysine bound tetrasulfonato-aluminum phthalocyanine entrapped nanoparticles (PCNP) and polylysine bound tetrasulfonato-aluminum phthalocyanine entrapped nanoparticles coated with a second, porphyrin based, photosensitizer (PCNP-P) to enhance the capacity for ROS generation, and hence therapeutic potential. The mean sizes of these particles were 45 ± 10 nm and 95 ± 10 nm respectively. Uptake of the nanoparticles by human Caucasian colon adenocarcinoma cells (HT29) was determined by flow cytometry and confocal microscopy. Cell viability assays using PCNP-P and PCNP corresponding to the minimum uptake time (<5 min) and maximum uptake time (25 h) demonstrated that these cancer cells can be damaged by light activation of these photodynamic nanoparticles both in the external media and after internalization. The results suggest that, in order to induce photodynamic damage, the nanoparticles need only to be associated with the tumor cell closely enough to deliver singlet oxygen: their internalization within target cells may not be necessary. Clinically, this could be of great importance as it may help to combat the known ability of many cancer cells to actively expel conventional anticancer drugs.
authors.affiliation: Department of Chemistry, University of Hull, Cottingham Road, Kingston-upon-Hull HU67RX, United Kingdom.
authors.forename: Maheshika
authors.initials: M
authors.lastname: Kuruppuarachchi
authors.forename: Huguette
authors.initials: H
authors.lastname: Savoie
authors.forename: Ann
authors.initials: A
authors.lastname: Lowry
authors.forename: Cristina
authors.initials: C
authors.lastname: Alonso
authors.forename: Ross W
authors.initials: RW
authors.lastname: Boyle
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry; D054833:Isoindoles; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D007211:Indoles; D054833:Isoindoles; D017319:Photosensitizing Agents; D011107:Polylysine; D000099166:Polyacrylamides; C013647:phthalocyanine