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1.
ACS Nano ; 13(10): 11249-11262, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31566945

RESUMO

Here, a protein farnesyltransferase (PFTase)-driven plasma membrane (PM)-targeted chimeric peptide, PpIX-C6-PEG8-KKKKKKSKTKC-OMe (PCPK), was designed for PM-targeted photodynamic therapy (PM-PDT) and enhanced immunotherapy via 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.

2.
Adv Mater ; 31(19): e1901179, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30924234

RESUMO

Neutrophils are powerful effector leukocytes that play an important role in innate immune systems for opposing tumor progression and ameliorating pathogen infections. Inspired by their distinct functions against tumors and infections, the artificial "super neutrophils" are proposed with excellent inflammation targeting and hypochlorous acid (HClO) generation characteristics for targeting and eliminating malignant tumor cells and pathogens. The "super neutrophils" are fabricated by embedding glucose oxidase (GOx) and chloroperoxidase (CPO) into zeolitic imidazolate framework-8 (ZIF-8) for HClO generation via enzymatic cascades, and then encapsulating them with the neutrophil membrane (NM) for inflammation targeting. In vitro and in vivo results indicate that these artificial "super neutrophils" can generate seven times higher reactive HClO than the natural neutrophils for eradicating tumors and infections. The "super neutrophils" demonstrated here with easy fabrication and good neutrophil-mimicking property exhibit great potential for biomedical applications.


Assuntos
Anti-Inflamatórios/química , Antineoplásicos/química , Materiais Biomiméticos/química , Ácido Hipocloroso/metabolismo , Ácido Hipocloroso/farmacologia , Membranas Artificiais , Animais , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cloreto Peroxidase , Enzimas Imobilizadas/metabolismo , Glucose Oxidase/metabolismo , Humanos , Pulmão , Camundongos Endogâmicos BALB C , Nanoestruturas/química , Neutrófilos/química , Propriedades de Superfície , Zeolitas/química
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