Boosting 5-ALA-based photodynamic therapy by a liposomal nanomedicine through intracellular iron ion regulation.
Acta Pharm Sin B
; 11(5): 1329-1340, 2021 May.
Article
em En
| MEDLINE
| ID: mdl-34094837
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.
5-ALA, 5-aminolevulinic acid; 5-Aminolevulinic acid; ALKBH2; Biotransformation interference; CH, cholesterol; CLs, custom liposomes; Ce6, chlorine e6; DFO, deferoxamine; DNA repair inhibition; DOPC, 1,2-dioleoyl-sn-glycero-3-phosphocholine; DOPE, dioleoyl phosphatidy lethanolamine; DPPC, dipalmitoyl-sn-glycero-3-phosphocholine; Drug delivery; FBS, fetal bovine serum; H&E, hematoxylin and eosin; Iron ion regulation; LMPA, low melting point agarose; MFLs, membrane fusion liposomes; Membrane fusion liposomes; NMPA, normal melting point agarose; PDT, photodynamic therapy; PS, photosensitizers; Photodynamic therapy; PpIX, protoporphyrin IX; ROS, reactive oxygen species; SM, sphingomyelin; TUNEL, terminal deoxynucleotidyl trans-ferase dUTP nick end labeling; calcein-AM/PI, calcein-AM/ propidiumiodide
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Acta Pharm Sin B
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China