ABSTRACT
5-Aminolevulinic acid (5-ALA) has been approved for clinical photodynamic therapy (PDT) due to its negligible photosensitive toxicity. However, the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells. Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair, a liposomal nanomedicine (MFLs@5-ALA/DFO) with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA, which was prepared by co-encapsulating 5-ALA and DFO (deferoxamine, a special iron chelator) into the membrane fusion liposomes (MFLs). MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery. MFLs@5-ALA/DFO could efficiently reduce iron ion, thus blocking the biotransformation of photosensitive protoporphyrin IX (PpIX) to heme, realizing significant accumulation of photosensitivity. Meanwhile, the activity of DNA repair enzyme was also inhibited with the reduction of iron ion, resulting in the aggravated DNA damage in tumor cells. Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.
ABSTRACT
The damage of tissue increases dramatically after reperfusion of blood supply to ischemic tissues.Immune response is one of the key reasons of ischemia-reperfusion injury.Th1 /Th2 generally stays balanced in normal states.Under the envi-ronment of ischemia reperfusion,Th1 /Th2 shifting let Th1 domi-nant to mediate cellular immunity.Excessive immune reaction may cause cell apoptosis and tissue damage.Recent studies showed that induction of transferring Th1 dominant to Th2 domi-nant was feasible for the treatment of ischemia-reperfusion inju-ry.With the progress of modern drug development paradigm“multi-composition,multi-target”,Chinese medicine has advan-tages in treating complex diseases.This paper summarizes the research of the relationship between Th1 /Th2 imbalance and is-chemia-reperfusion injury,together with the prospects of tradi-tional Chinese medicine with multi-target effect in ischemia-reperfusion injury.
ABSTRACT
Myocardial ischemia/reperfusion injury ( MI/RI) is a pathophysiological phenomenon commonly seen during thromboly-sis, percutaneous transluminal coronary angioplasty ( PTCA ) , and coronary artery bypass grafting ( CABG ) . It is defined as restoration of blood flow to a previously ischemic region followed by complex pathological events leading to tissue injury greater than the original ischemic insult. Many experimental interven-tions have been reported to protect the ischemic myocardium in experimental animals; however, with the exception of early reperfusion, none has been translated into clinical practice. The root of Panax notoginseng ( Burk. ) F. H. Chen ( PN) is one of the iconic herbs in traditional Chinese medicine. Traditional pharmacopeia recommended it among the most efficacious herbs for‘promoting blood circulation ’ and hemostasis. Inspired by this, in the last decade, a large number of modern investigators made substantial efforts to search the PN activities against a vari-ety of MIRI. The systematic review was performed according to the protecting drug of the MIRI development guidelines.