Enzyme-Driven
Membrane-Targeted Chimeric Peptide for
Enhanced Tumor Photodynamic Immunotherapy
Chi Zhang
Fan Gao
Wei Wu
Wen-Xiu Qiu
Lu Zhang
Runqing Li
Ze-Nan Zhuang
Wuyang Yu
Han Cheng
Xian-Zheng Zhang
10.1021/acsnano.9b04315.s001
https://acs.figshare.com/articles/journal_contribution/Enzyme-Driven_Membrane-Targeted_Chimeric_Peptide_for_Enhanced_Tumor_Photodynamic_Immunotherapy/9929816
Here,
a protein farnesyltransferase (PFTase)-driven plasma membrane
(PM)-targeted chimeric peptide, PpIX-C<sub>6</sub>-PEG<sub>8</sub>-KKKKKKSKTKC-OMe (PCPK), was designed for PM-targeted photodynamic
therapy (PM-PDT) and enhanced immunotherapy <i>via</i> tumor
cell PM damage and fast release of damage-associated molecular patterns
(DAMPs). The PM targeting ability of PCPK originates from the cellular
K-Ras signaling, which occurs exclusively to drive the corresponding
proteins to PM by PFTase. With the conjugation of the photosensitizer
protoporphyrin IX (PpIX), PCPK could generate cytotoxic reactive oxygen
species to deactivate membrane-associated proteins, initiate lipid
peroxidation, and destroy PM with an extremely low concentration (1
μM) under light irradiation. The specific PM damage further
induced the fast release of DAMPs (high-mobility group box 1 and ATP),
resulting in antitumor immune responses stronger than those of conventional
cytoplasm-localized PDT. This immune-stimulating PM-PDT strategy also
exhibited the inhibition effect for distant metastatic tumors when
combined with programmed cell death receptor 1 blockade therapy.
2019-10-02 15:04:33
PEG 8
inhibition effect
cytoplasm-localized PDT
Enhanced Tumor Photodynamic Immunotherapy
deactivate membrane-associated proteins
lipid peroxidation
PM damage
high-mobility group box 1
PM-targeted photodynamic therapy
cell death receptor 1 blockade therapy
immune-stimulating PM-PDT strategy
photosensitizer protoporphyrin
ATP
DAMP
light irradiation
protein farnesyltransferase
Enzyme-Driven Membrane-Targeted Chimeric Peptide
cytotoxic reactive oxygen species
PCPK
metastatic tumors
PpIX-C 6
tumor cell PM damage