Abstract
BackgroundPhotodynamic therapy (PDT) as promising alternative to conventional cancer treatments works by irradiation of a photosensitizer (PS) with light, which creates reactive oxygen species and singlet oxygen (1O2), that damage the tumor. However, a routine use is hindered by the PS’s poor water solubility and extended cutaneous photosensitivity of patients after treatment. In our study we sought to overcome these limitations by encapsulation of the PS m-tetrahydroxyphenylchlorin (mTHPC) into a biocompatible nanoemulsion (Lipidots).ResultsIn CAL-33 tumor bearing nude mice we compared the Lipidots to the existing liposomal mTHPC nanoformulation Foslip and the approved mTHPC formulation Foscan. We established biodistribution profiles via fluorescence measurements in vivo and high performance liquid chromatography (HPLC) analysis. All formulations accumulated in the tumors and we could determine the optimum treatment time point for each substance (8 h for mTHPC, 24 h for Foslip and 72 h for the Lipidots). We used two different light doses (10 and 20 J/cm2) and evaluated immediate PDT effects 48 h after treatment and long term effects 14 days later. We also analyzed tumors by histological analysis and performing reverse transcription real-time PCR with RNA extracts. Concerning tumor destruction Foslip was superior to Lipidots and Foscan while with regard to tolerance and side effects Lipidots were giving the best results.ConclusionsWe could demonstrate in our study that nanoformulations are superior to the free PS mTHPC. The development of a potent nanoformulation is of major importance because the free PS is related to several issues such as poor bioavailability, solubility and increased photosensibility of patients. We could show in this study that Foslip is very potent in destroying the tumors itself. However, because the Lipidots' biocompatibility is outstanding and superior to the liposomes we plan to carry out further investigations and protocol optimization. Both nanoformulations show great potential to revolutionize PDT in the future.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0223-8) contains supplementary material, which is available to authorized users.
Highlights
Photodynamic therapy (PDT) as promising alternative to conventional cancer treatments works by irradiation of a photosensitizer (PS) with light, which creates reactive oxygen species and singlet oxygen (1O2), that damage the tumor
The powerful chlorin PS m-tetrahydroxyphenylchlorin is a well characterized substance and was highly successful in various in vitro, in vivo studies and clinical trials which has led to its approval for palliative treatment of head and neck cancer in Europe [17,18,19,20]
Very promising its routine use in the clinic is hampered by poor water solubility which leads to aggregation, problematic systemic administration and suboptimal biodistribution
Summary
Photodynamic therapy (PDT) as promising alternative to conventional cancer treatments works by irradiation of a photosensitizer (PS) with light, which creates reactive oxygen species and singlet oxygen (1O2), that damage the tumor. PDT is a strictly local modality that offers certain advantages over established anti-cancer regimes It is e.g. minimally invasive, does not have a maximal lifetime dose and can be repeated [1], gives an excellent cosmetic and functional outcome [10], does not produce drug resistance [11], and is not associated with severe systemic side effects [12]. PSs are preferentially taken up by malignant cells and exhibit an inherent selectivity [13]. Extended photosensitivity of patients after treatment impairs applicability [5, 21]
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