Zwitterionic stealth peptide-capped 5-aminolevulinic acid prodrug nanoparticles for targeted photodynamic therapy.
5-Aminolevulinic acid (ALA) is a FDA-approved photodynamic therapy (PDT) precursor of protoporphyrin IX (PpIX) used for treating various cancers. However, the internalization of ALA is a big challenge due to its hydrophilic nature and low specificity to cancer cells. In this work, ALA conjugated prodrug nanoparticles were prepared by conjugation of thiolated stealth peptide sequence CPPPPEKEKEKEKEKEDGR and hydrazone-containing ALA to gold nanoparticles (AuNPs). Remarkable anti-fouling ability of ALA prodrug nanoparticles in complex environment was achieved owing to the zwitterionic stealth peptide sequence EKEKEKEKEK. The release of ALA could be greatly accelerated upon incubation of ALA prodrug nanoparticles in lysosomal/endosomal pH (pH 5.5). Meanwhile, the cellular internalization could be greatly enhanced by RGD moieties. MTT results demonstrated that ALA prodrug nanoparticles exhibited better photodynamic cytotoxicity than free ALA after light irradiation, suggesting enhanced photodynamic therapeutic efficacy.
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Jina
J
Wu
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Ye
Y
Lin
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Huan
H
Li
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address: jinqiao@zju.edu.cn.
Qiao
Q
Jin
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Jian
J
Ji
D000595:Amino Acid Sequence; D000622:Aminolevulinic Acid / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D065546:Drug Liberation; D006046:Gold / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008027:Light; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology; D011524:Protoporphyrins / Q000737:chemistry / Q000494:pharmacology*
D010455:Peptides; D017319:Photosensitizing Agents; D011355:Prodrugs; D011524:Protoporphyrins; D006046:Gold; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
ALA; Nanocarrier; Photodynamic therapy; Prodrug; Zwitterionic