Effects of light irradiation upon photodynamic therapy based on 5-aminolevulinic acid–gold nanoparticle conjugates in K562 cells via singlet oxygen generation

Abstract

Purpose: As a precursor of the potent photosensitizer protoporphyrin IX (PpIX), 5-aminolevulinic acid (5-ALA), was conjugated onto cationic gold nanoparticles (GNPs) to improve the efficacy of photodynamic therapy (PDT). Methods: Cationic GNPs reduced by branched polyethyleneimine and 5-ALA were conjugated onto the cationic GNPs by creating an electrostatic interaction at physiological pH. The efficacy of ALA-GNP conjugates in PDT was investigated under irradiation with a mercury lamp (central wavelength of 395 nm) and three types of light-emitting diode arrays (central wavelengths of 399, 502, and 621 nm, respectively). The impacts of GNPs on PDT were then analyzed by measuring the intracellular PpIX levels in K562 cells and the singlet oxygen yield of PpIX under irradiation. Results: The 2 mM ALA-GNP conjugates showed greater cytotoxicity against K562 cells than ALA alone. Light-emitting diode (505 nm) irradiation of the conjugates caused a level of K562 cell destruction similar to that with irradiation by a mercury lamp, although it had no adverse effects on drug-free control cells. These results may be attributed to the singlet oxygen yield of PpIX, which can be enhanced by GNPs. Conclusion: Under irradiation with a suitable light source, ALA-GNP conjugates can effectively destroy K562 cells. The technique offers a new strategy of PDT.

Tunable phosphatase-sensitive stable prodrugs of 5-aminolevulinic acid for tumor fluorescence photodetection

“…The major reasoning is that increased lipophilicity potentially improves the passage through biological membranes thus increasing intracellular substrate concentration for heme biosynthesis. Recently, substantial efforts have also been directed towards nanocarriers loaded [20][21][22][23][24] or conjugated [25][26][27][28] with 5-ALA. These approaches tackle some of the pharmacokinetic and specificity drawbacks of 5-ALA but have so far failed to produce a clinical candidate for the improved delivery of 5-ALA mostly due to high 5-ALA loading and delivery required for this type of FPD or PDT.…”

Comparative study of X-ray treatment and photodynamic therapy by using 5-aminolevulinic acid conjugated gold nanoparticles in a melanoma cell line

“…Our findings in PDT on the Mel-Rm cell line showed, ED50 was reduced from 136.2 J/cm 2 for 5ALA to 56.2 J/cm 2 in the presence of the conjugate. Xu et al produced another study that has also shown the increasing efficiency of PDT (Xu et al 2012). This indicates that the presence of the conjugate leads to a more than two-fold increase in the efficiency of PDT on Mel-Rm cells in comparison to 5ALA alone.…”

“…Protoporphyrin IX (PpIX) is produced in cells via the heme synthesis pathway, from the substrate aminolevulinic acid (5ALA), and is known as a high bio-compatible photosensitizer (Kim et al 2011, Sultan et al 2006. Previous studies have shown that gold nanoparticles can act as the carrier for 5ALA and in the presence of the 5ALA-conjugated gold nanoparticles will result in increased efficiency of PDT (Hainfeld et al 2004, Xu et al 2012. Therefore, the conjugate can be considered as an effective photosensitizer that approximately covers the first problem of PDT.…”

Enhancement of Cisplatin Efficacy by Gold Nanoparticles or Microwave Hyperthermia? An In Vitro Study on a Melanoma Cell Line

“…About the results achieved, one assumption is entrance of cisplatin in the presence of GNPs that facilitated. It has shown GNPs with a diameter less than 100 nm enhance endocytosis and permeability and retention effect (EPR) (37)(38)(39). This mechanism has often resulted in 10-fold or greater drug delivery to a tumor over conventional chemotherapy (40).…”