Combined chemotherapy and ALA-based photodynamic therapy in leukemic murine cells.

The effects of combined administration of doxorubicin (DOX) and vincristine (VCR), with 5-aminolevulinic acid photodynamic treatment (ALA-PDT), were analyzed in sensitive murine leukemic cell lines (LBR-) and DOX and VCR chemoresistant LBR-D160 and LBR-V160 cell lines. Low doses of DOX and VCR increased anti-cancer effect of ALA-PDT in LBR-cells. Decrease in cell survival was higher when the combination VCR+ALA-PDT was used compared to DOX+ALA-PDT.

Comparation of liposomal formulations of ALA Undecanoyl ester for its use in photodynamic therapy.

ALA administration has been used to induce the endogenous photosensitiser Protoporphyrin IX for photodynamic therapy (PDT) of tumours. However, the hydrophilic nature of ALA limits its ability to penetrate through skin restricting the use of ALA-PDT to superficial diseases. Lipophilic derivatives of ALA such as ALA Undecanoyl ester (Und-ALA) were designed to have better diffusing properties.

Sustained and efficient porphyrin generation in vivo using dendrimer conjugates of 5-ALA for photodynamic therapy.

The use of endogenous protoporphyrin IX (PpIX) after administration of 5-aminolaevulinic acid (ALA) has led to many applications in photodynamic therapy (PDT). However the efficacy of ALA-PDT is sub-optimal for thicker tumours and improved ALA delivery and therapeutic response are required. We have investigated the conjugation of ALA to a second-generation dxcendrimer for enhancing porphyrin synthesis in vitro and in vivo in a murine tumour model using systemic i.

Characterisation of liposomes containing aminolevulinic acid and derived esters.

Liposomes of different compositions have been designed to improve delivery of aminolevulinic acid (ALA) and its esterified derivatives ALA-Hexyl ester (He-ALA) and ALA-Undecanoyl ester (Und-ALA) for its use in photodynamic therapy (PDT). Egg yolk phosphatidyl choline (PC), phosphatidic acid (PA) and phosphatidyl glycerol (PG) were employed in the preparation of the liposomes. Sonicated vesicles composed of PC, PC-PG (80:20) or PC-PA (80:20) containing ALA or derivatives were obtained and purified by a minicolumn centrifugation method.

5-aminolevulinic acid-mediated photodynamic therapy on Hep-2 and MCF-7c3 cells.

The cytotoxic effect of 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PPIX) on two human carcinoma cell lines, MCF-7c3 cells and Hep 2 cells, was studied. In both cell lines, PPIX content depends on the ALA concentration and incubation time. The maximal PPIX content was higher in the MCF-7c3 cells, reaching a value of 8 microg/10(6) cells, compared to the Hep-2 cells, which accumulated 3.

Use of ALA and ALA derivatives for optimizing ALA-based photodynamic therapy: a review of our experience.

5-Aminolevulinic acid (ALA)-based PDT has been gaining increased attention in the last ten years, and become an approved treatment modality for some cancers and other diseases. Different approaches to enhance this therapeutic modality are in progress, including the development of several drug delivery systems and the use of more lipophilic ALA derivatives. This paper focuses on our experience in this field.

Distribution of 5-aminolevulinic acid derivatives and induced porphyrin kinetics in mice tissues.

Purpose: Porphyrins synthesised from 5-aminolevulinic acid (ALA) have been successfully used for the photodiagnosis and photodynamic treatment of cancer. To find a more efficient pro-photosensitiser, we synthesised two ALA esters: R,S-ALA-2-(hydroxymethyl)tetrahydropyranyl ester (THP-ALA) and ALA-Undecanoyl ester (Und-ALA).

Methods: In mice bearing a subcutaneous mammary adenocarcinoma, we studied the distribution of the porphyrins formed from these esters in tissues after systemic administration, to establish if these esters are retained in any specific tissue, which could potentially be targeted for photodynamic treatment with ALA derivatives.

Photodynamic therapy: regulation of porphyrin synthesis and hydrolysis from ALA esters.

Photodynamic therapy (PDT) is a tool for the treatment of certain cancerous and pre-cancerous conditions. The natural precursor of porphyrins 5-aminolevulinic acid (ALA) has been extensively used as a pro-photosensitiser in PDT. ALA's poor permeability has been enhanced by chemical esterification with aliphatic alcohols.

Investigation of a novel dendritic derivative of 5-aminolaevulinic acid for photodynamic therapy.

Photodynamic therapy is a treatment for malignant and certain non-malignant lesions that involves administration of a photosensitising drug. The use of 5-aminolaevulinic acid-induced porphyrins has become one of the most active fields of photodynamic therapy research. Since the efficacy of the treatment is somewhat limited by the hydrophilic nature of 5-aminolaevulinic acid, chemical modifications such as esterification with aliphatic alcohols have been made to induce higher porphyrin production.

No cross-resistance between ALA-mediated photodynamic therapy and nitric oxide.

Photodynamic therapy (PDT) interactions with nitric oxide (NO) are not well understood. In this work, we attempted to elucidate whether NO cytotoxicity and PDT from aminolevulinic acid (ALA) have independent cell damage mechanisms. We employed the murine mammary adenocarcinoma cell line LM3 and its NO-resistant variant LM3-SNP obtained after successive exposures to sodium nitroprusside (SNP).

Sensitivity to ALA-PDT of cell lines with different nitric oxide production and resistance to NO cytotoxicity.

In this work, we studied the in vitro interactions between aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) and nitric oxide (NO), as well as the interactions between ALA, porphyrins and some NO donors and precursors. We employed three murine adenocarcinoma cell lines: LM2, which does not produce NO; LM3, which produces NO, and LM3-SNP, a variant of LM3 resistant to NO producing the same amount of NO as the parental. We did not find cross-resistance between NO-induced cytotoxicity and ALA-PDT.

Aminolevulinic acid: from its unique biological function to its star role in photodynamic therapy.

Porphyrins are molecules essential for life. They are involved in the key processes of photosynthesis and respiration. The biosynthesis of tetrapyrroles in all living cells occurs through several steps where the formation of aminolevulinic acid (ALA) is the first committed intermediate.

A method for separating ALA from ALA derivatives using ionic exchange extraction.

Photodynamic therapy using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX is a recent approach to detect and treat some malignancies. The use of lipophilic derivatives of ALA has been exploited in the last years to enhance ALA penetration. In this paper, we describe the application of the Mauzerall and Granick's method [J.