Photodynamic Effects of Zinc(II) Phthalocyanine‐Loaded Polymeric Micelles in Human Nasopharynx KB Carcinoma Cells

Abstract

A major difficulty in photodynamic therapy is the poor solubility of the photosensitizer (PS) under physiological conditions which correlates with low bioavailability. PS aggregation leads to a decrease in the photodynamic efficiency and a more limited activity in vitro and in vivo. To improve the aqueous solubility and reduce the aggregation of 2,9(10),16(17),23(24)-tetrakis[(2-dimethylamino)ethylsulfanyl]phthal-ocyaninatozinc(II) (Pc9), the encapsulation into four poloxamine polymeric micelles (T304, T904, T1107 and T1307) displaying a broad spectrum of molecular weight and hydrophilic-lipophilic balance was investigated. The aqueous solubility of Pc9 was increased up to 30 times. Morphological evaluation showed the formation of Pc9-loaded spherical micelles in the nanosize range. UV/Vis and fluorescence studies indicated that Pc9 is less aggregated upon encapsulation in comparison with Pc9 in water-DMSO 2% and remained photostable. Pc9-loaded micelles generated singlet molecular oxygen in high yields. Photocytotoxicity assays using human nasopharynx KB carcinoma cells confirmed that the encapsulation of Pc9 in T1107 and T1307 increases its photocytotoxicity by 10 times in comparison with the free form in water-DMSO. In addition, Pc9 incorporated into cells was mainly localized in lysosomes.

Novel Poly(Ethylene Oxide)-b-Poly(Propylene Oxide) Copolymer-Glucose Conjugate by the Microwave-Assisted Ring Opening of a Sugar Lactone

“…PEO–PPOs are commercially available in two different molecular architectures, the linear poloxamers (Pluronic®) and branched poloxamines (Tetronic®), and a broad spectrum of molecular weights and hydrophilic–lipophilic balances . Our group has extensively investigated the use of pristine and modified PEO–PPOs for the encapsulation, release, and targeting of drugs by the topical, the oral, the parenteral, and the intranasal route and also the PEO–PPO‐mediated inhibition of the activity of pumps of the ATP‐binding cassette superfamily . Irrespective of their potential, the ability of pristine PMs to target specific cell types is remarkably constrained due to the PEGylated nature of the surface that minimizes interaction with phagocytic cells.…”

Developments in PDT Sensitizers for Increased Selectivity and Singlet Oxygen Production

“…Polymeric micelles are made of amphiphilic block or graft copolymers that form spontaneously in aqueous media due to thermodynamically-favored aggregation above the critical micelle concentration (CMC) [65]. Micelles with lower CMC levels have higher thermodynamic stability, which can be obtained by increasing the hydrophobic section of the amphiphiles [65,66].…”

“…Micelles with lower CMC levels have higher thermodynamic stability, which can be obtained by increasing the hydrophobic section of the amphiphiles [65,66]. Below the CMC level polymer chains tend to remain in the monomolecular state.…”

“…Also, polymeric micelles can solubilize a larger amount of the PDT agent and they are suitable for parenteral administration [65]. Micelles can be made of amphiphilic peptides.…”

Phototoxicity of Liposomal Zn- and Al-phthalocyanine Against Cervical and Oral Squamous Cell Carcinoma Cells In Vitro

“…We also examined the effect of FR-targeted liposomal ZnPc using highly FR-positive HeLa cells [ 25 , 26 ]. We did not use KB cells, used often as a model for oral cancer cells and FR-positive cells [ 18 , 19 , 21 , 22 , 24 , 27 – 29 ]. The nasopharyngeal KB cell line, originally isolated in 1955 from a human epidermoid carcinoma of the mouth, was subsequently found to be contaminated by HeLa cells (cervical adenocarcinoma), based on isoenzyme analysis, HeLa marker chromosomes, and DNA fingerprinting [ 30 , 31 ].…”