Abstract

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT.

Highlights

  • 5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX)

  • 5-Aminolevulinic acid (5-ALA) is a naturally occurring amino acid derivative that acts as a precursor of protoporphyrin IX (PpIX) [1–3]. 5-ALA administration to animals, including humans, leads to the synthesis of PpIX, especially in tumors [4–7]

  • We summarized past and recent in vitro experiments investigating 5-ALA photodynamic therapy (PDT) for cancer cells and compared these data by calculating the effectiveness value

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Summary

Introduction

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. PpIX is activated by violet light (405 nm) or orange-red light (635 nm), subsequently emitting red fluorescence (620–710 nm) or generating reactive oxygen species (ROS) [8]. These features can potentially be used to visualize or kill cancer. 5-ALA has been clinically tested for photodynamic diagnosis (PDD) during surgery to visualize cancer cells by fluorescence and photodynamic therapy (PDT) to target unfavorable neoplasms by increasing ROS production [9,10]. 5-ALA has been clinically approved by the

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