Aminolevulinic acid dendrimers in the treatment of cancer and atheromatous disease

M. VAINMAN 1 , L. RODRIGUEZ 1 , G. DI VENOSA 1 , L. MAMONE 1 , L. GANDARA 1 , P. VALLECORSA 1 , M. V. ROSSETTI 1 , A. BATLLE 1 , S. BATTAH 2 , A. CASAS 1

Lucerna

Congreso; Annual Assembly SSCC/Congress P&P; 2013

Swiss Society of Clinical Chemistry

Photodynamic therapy (PDT) is an anticancer treatment that involvesadministration of a tumour-localising photosensitizer and its subsequentactivation by visible light to result primarily in singlet oxygen ?induced photodamage to the tumour. The photosensitizer absorbslight and in the presence of oxygen transfers energy, producing shortlivedcytotoxic oxygen species such as singlet oxygen or other oxygenradicals.The use of endogenous protoporphyrin IX (PpIX) after administrationof 5-aminolaevulinic acid (ALA) has led to many applicationsin PDT. However the efficacy of ALA-PDT is sub-optimal for thickertumours and improved ALA delivery and therapeutic response arerequired. We have investigated the conjugation of ALA to a secondgenerationdendrimer for enhancing porphyrin synthesis in vitro.Rec ent advances in laser technology, and endovascular light deliverysystems have broadened the scope of PDT to include atheroscleroticapplications, so called Photoangioplasty.The aim of this work was to evaluate in vitro the ability of ALAdendrimers 6m-ALA and 9m-ALA to photosensitize cancer cells andmacrophages. We have focused on selectivity, since the main aimis to damage macrophage component of the atheromatous plaquewhile leaving intact the vasculature structures.We have employed the LM3 mammary carcinoma, the Raw 264.7macrophage and HMEC-1 microvasculature cell lines. Porphyrinssynthesised from the three cell lines were evaluated fluorimetrically.LM3, HMEC-1 and Raw 264.7 cell lines exposed to both 6m-ALAand 9m-ALA reached complete ALA release from the nanocarriers 24hr after incubation.On the other hand, porphyrin synthesis is higher at 3 hr in macrophages(6m-ALA = 52 ± 6 μ g porphyrins/105 cells, 9m-ALA = 59 ±7 μ g porph./105 cells) as compared to the endothelial cell line (6m-ALA = 28 ± 3 μ g porph./105 cells, 9m-ALA = 27 ± 2 μ g porph/105 cells)employing 0.2 mM concentrations (p < 0,01), thus demonstratingselectivity of dendrimers for macrophages.In tumour LM3 cells, PpIX from dendrimers is much higher ascompared to ALA (ALA = 48 ± 6 μ g porph./105 cells, 6m-ALA = 168 ±19 μ g porph/105 cells, 9m-ALA = 176 ± 20 μ g porph/105 cells) at 3 hremploying 0.025 mM concentrations, showing the that dendrimersare much efficient than ALA for use in PDT of cancer.