Enhanced porphyrin accumulation using dendritic derivatives of 5-aminolaevulinic acid for photodynamic therapy: An in vitro study

Battah, Sinan; O’Neill, Sophie; Edwards, Christine; Balaratnam, Sherina; Dobbin, Paul S.; MacRobert, Alexander J.

doi:10.1016/j.biocel.2006.02.001

Cited by 52 publications

(42 citation statements)

References 35 publications

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“…The first step towards nano-sized PS formulations were made through the preparation of dendritic [80,81], glyco [82,83], amino acid [84] and peptide [85] functionalized porphyrins. Initially, many of these studies were just aimed at increasing the water solubility, formulation properties and targeting of the PS [86].…”

Section: Ps Linkermentioning

confidence: 99%

Nanodrug applications in photodynamic therapy

Paszko

Ehrhardt

Senge

et al. 2011

Photodiagnosis and Photodynamic Therapy

326

215

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SummaryPhotodynamic therapy (PDT) has developed over last century and is now becoming a more widely used medical tool having gained regulatory approval for the treatment of various diseases such as cancer and macular degeneration. It is a two-step technique in which delivery of a photosensitizing drug is followed by irradiation of light. Activated photosensitizers transfer energy to molecular oxygen which results in generation of reactive oxygen species which in turn cause cells apoptosis or necrosis. Although this modality has significantly improved quality of life and survival time for many cancer patients it still offers significant potential for further improvement. In addition to the development of new PDT drugs, the use of nanosized carriers for photosensitizers is a promising approach which might improve the efficiency of photodynamic activity and which can overcome many side effects associated with classic photodynamic therapy. This review aims at highlighting the different types of nanomedical approaches currently used in PDT and outlines future trends and limitations of nanodelivery of photosensitizers. PDT -photodynamic therapy; PGA -poly(glycolic acid); PGLA -poly(D,L-lactide-coglycolide); PLA -poly(lactic acid); PS -photosensitizer; PEG -polyethylene glycol; ALA  aminolevulinic acid; m-THPC  5,10,15,20-tetra-(m-hydroxyphenyl)chlorine; m-THPP  meso-tetra(p-hydroxyphenyl); PpIX  protoporphyrin; Hp  hematoporphyrin; Pc4  silicon phthalocyanine; Ig  immunoglobulin; Tf  transferrin; TfR  transferrin receptor; VEGF  vascular endothelial growth factor; EPR  enhanced permeability and retention effect; FRET  fluorescence resonance energy transfer; MRI  magnetic resonance imaging; RES  reticuloendothelial system; ROS  reactive oxygen species; NP  nanoparticle; ND -nanodiamonds; SNP  silica nanoparticle; AMD  age-related macular degeneration; CNV  choroidal neovascularization; PTT  photothermal therapy;

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Section: Ps Linkermentioning

confidence: 99%

Nanodrug applications in photodynamic therapy

Paszko

Ehrhardt

Senge

et al. 2011

Photodiagnosis and Photodynamic Therapy

326

215

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“…The fluorescence signal from each well was measured with a Perkin-Elmer LS 50B fluorescence spectrometer coupled to an automated plate reader (Perkin-Elmer) using 410 nm excitation and 635 nm emission wavelengths with slit widths set to 10 nm and the internal 530 nm long-pass filter used on the emission side; spectral scans were recorded between 600 and 750 nm to check for presence of any porphyrins other than PpIX (14). The mean fluorescence intensity (expressed in arbitrary units) was calculated after subtraction of the control values.…”

Section: Fluorescence Pharmacokineticsmentioning

confidence: 99%

5-Aminolaevulinic acid peptide prodrugs enhance photosensitization for photodynamic therapy

Bourré

Giuntini²,

Eggleston³

et al. 2008

Molecular Cancer Therapeutics

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Intracellular porphyrin generation following administration of 5-aminolaevulinic acid (ALA) has been widely used in photodynamic therapy for a range of malignant and nonmalignant lesions. However, ALA is relatively hydrophilic and lacks stability at physiologic pH, limiting its bioavailability. We have investigated more lipophilic, uncharged ALA-peptide prodrugs based on phenylalanyl-ALA conjugates, which are water soluble and chemically stable for improving ALA delivery. Pharmacokinetics of the induced protoporphyrin IX (PpIX) were studied in transformed PAM212 keratinocyte cells and pig skin explants. The intracellular porphyrin production was substantially increased with Ac-L-Phe-ALA-Me (compound 1) and Ac-LPhe-ALA (compound 3) compared with equimolar ALA: after 6-h incubation, the PpIX fluorescence measured using 0.01 mmol/L of compound 1 was enhanced by a factor of 5 compared with ALA. Phototoxicity results showed good correlation with PpIX levels, giving a LD 50 (2.5 J/cm 2 ) of 25 Mmol/L for ALA, 6 Mmol/L for 5-aminolaevulinic hexyl ester, and 2.6 Mmol/L for compound 1, which exhibited the highest phototoxicity. However, these results were stereospecific because the corresponding D-enantiomer, Ac-D-Phe-ALA-Me (compound 2), induced neither porphyrin synthesis nor phototoxicity. PpIX levels were considerably reduced when cells were incubated with compound 1 at low temperatures, consistent with active transport. In pig skin explants, compound 1 induced higher porphyrin fluorescence than ALA by a factor of 3. These results show that water-soluble peptide prodrugs of ALA can greatly increase its cellular uptake, generating more intracellular PpIX and improved tumor cell photosensitization. The derivatives are comparable in efficacy with 5-aminolaevulinic hexyl ester but less toxic and more stable at physiologic pH. [Mol Cancer Ther 2008;7(6):1720 -9]

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“…A preliminary investigation of dendritic ALA derivatives showed that they were capable of delivering ALA to cells for conversion into PpIX (20). The ALA residues were attached via ester linkages, which were then cleaved enzymatically within the cells to liberate the ALA. Several smaller dendritic ALA prodrugs have also been investigated recently to compare the effect of changes in the molecular structure (21,22).…”

Section: Introductionmentioning

confidence: 99%

Macromolecular delivery of 5-aminolaevulinic acid for photodynamic therapy using dendrimer conjugates

Battah

Balaratnam

Casas

et al. 2007

Molecular Cancer Therapeutics

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Intracellular porphyrin generation following administration of 5-aminolaevulinic acid (5-ALA) has been widely used in photodynamic therapy. However, cellular uptake of 5-ALA is limited by its hydrophilicity, and improved means of delivery are therefore being sought. Highly branched polymeric drug carriers known as dendrimers present a promising new approach to drug delivery because they have a well-defined structure capable of incorporating a high drug payload. In this work, a dendrimer conjugate was investigated, which incorporated 18 aminolaevulinic acid residues attached via ester linkages to a multipodent aromatic core. The ability of the dendrimer to deliver and release 5-ALA intracellularly for metabolism to the photosensitizer, protoporphyrin IX, was studied in the transformed PAM 212 murine keratinocyte and A431 human epidermoid carcinoma cell lines. Up to an optimum concentration of 0

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Enhanced porphyrin accumulation using dendritic derivatives of 5-aminolaevulinic acid for photodynamic therapy: An in vitro study

Cited by 52 publications

References 35 publications

Nanodrug applications in photodynamic therapy

Nanodrug applications in photodynamic therapy

5-Aminolaevulinic acid peptide prodrugs enhance photosensitization for photodynamic therapy

Macromolecular delivery of 5-aminolaevulinic acid for photodynamic therapy using dendrimer conjugates

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