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Polyacrylamide nanoparticles as a delivery system in photodynamic therapy

Kuruppuarachchi, Maheshika; Lowry, Ann; Savoie, Huguette; Alonso, Cristina; Boyle, Ross W.

Authors

Maheshika Kuruppuarachchi

Ann Lowry

Huguette Savoie

Cristina Alonso

Ross W. Boyle



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 (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.

Citation

Kuruppuarachchi, M., Lowry, A., Savoie, H., Alonso, C., & Boyle, R. W. (2011). Polyacrylamide nanoparticles as a delivery system in photodynamic therapy. Molecular pharmaceutics, 8(3), 920-931. https://doi.org/10.1021/mp200023y

Journal Article Type Article
Acceptance Date Mar 16, 2011
Online Publication Date Mar 16, 2011
Publication Date Jun 6, 2011
Deposit Date Nov 13, 2014
Publicly Available Date Nov 13, 2014
Journal Molecular Pharmaceutics
Print ISSN 1543-8384
Electronic ISSN 1543-8392
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 8
Issue 3
Pages 920-931
DOI https://doi.org/10.1021/mp200023y
Keywords PDT; porphyrins; phthalocyanine; nanoparticles; drug delivery; localized embedding pebbles; drug-delivery; living cells; cancer-therapy; macrophage endocytosis; optical nanosensors; oxygen photosensitizers; mechanisms; porphyrin,
Public URL https://hull-repository.worktribe.com/output/463242

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