Abstract
BackgroundPhotosensitizers are used in photodynamic therapy (PDT) to destruct tumor cells, however, their limited solubility and specificity hampers routine use, which may be overcome by encapsulation. Several promising novel nanoparticulate drug carriers including liposomes, polymeric nanoparticles, metallic nanoparticles and lipid nanocomposites have been developed. However, many of them contain components that would not meet safety standards of regulatory bodies and due to difficulties of the manufacturing processes, reproducibility and scale up procedures these drugs may eventually not reach the clinics. Recently, we have designed a novel lipid nanostructured carrier, namely Lipidots, consisting of nontoxic and FDA approved ingredients as promising vehicle for the approved photosensitizer m-tetrahydroxyphenylchlorin (mTHPC).ResultsIn this study we tested Lipidots of two different sizes (50 and 120 nm) and assessed their photodynamic potential in 3-dimensional multicellular cancer spheroids. Microscopically, the intracellular accumulation kinetics of mTHPC were retarded after encapsulation. However, after activation mTHPC entrapped into 50 nm particles destroyed cancer spheroids as efficiently as the free drug. Cell death and gene expression studies provide evidence that encapsulation may lead to different cell killing modes in PDT.ConclusionsSince ATP viability assays showed that the carriers were nontoxic and that encapsulation reduced dark toxicity of mTHPC we conclude that our 50 nm photosensitizer carriers may be beneficial for clinical PDT applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0221-x) contains supplementary material, which is available to authorized users.
Highlights
Photosensitizers are used in photodynamic therapy (PDT) to destruct tumor cells, their limited solubility and specificity hampers routine use, which may be overcome by encapsulation
Estimated from the whole excipients initially incorporated in the Lipidot formulation, mTHPC was loaded in our study at 2.8 and 1.0 % w/w for 50 and 120 nm particles, respectively (Table 1)
Monolayer cultures and spheroids, we found that free mTHPC was taken up in a shorter time frame compared to mTHPC encapsulated into Lipidots
Summary
Photosensitizers are used in photodynamic therapy (PDT) to destruct tumor cells, their limited solubility and specificity hampers routine use, which may be overcome by encapsulation. Several promising novel nanoparticulate drug carriers including liposomes, polymeric nanoparticles, metallic nanoparticles and lipid nanocomposites have been developed. Many of them contain components that would not meet safety standards of regulatory bodies and due to difficulties of the manufacturing processes, reproducibility and scale up procedures these drugs may eventually not reach the clinics. We have designed a novel lipid nanostructured carrier, namely Lipidots, consisting of nontoxic and FDA approved ingredients as promising vehicle for the approved photosensitizer m-tetrahydroxyphenylchlorin (mTHPC). A wealth of publications report on the development of promising novel nanoparticulate drug carriers including liposomes [1], polymeric nanoparticles [2], metallic nanoparticles [3] and lipid nanocomposites [4].
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