Malaria biomimetic for tumor targeted drug delivery
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Malaria biomimetic for tumor targeted drug delivery. / Pihl, Jessica; Clausen, Thomas M; Zhou, Jiarong; Krishnan, Nishta; Ørum-Madsen, Maj S; Gustavsson, Tobias; Dagil, Robert; Daugaard, Mads; Choudhary, Swati; Foged, Camilla; Esko, Jeffrey D; Zhang, Liangfang; Fang, Ronnie H; Salanti, Ali.
In: ACS Nano, Vol. 17, No. 14, 2023, p. 13500–13509.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Malaria biomimetic for tumor targeted drug delivery
AU - Pihl, Jessica
AU - Clausen, Thomas M
AU - Zhou, Jiarong
AU - Krishnan, Nishta
AU - Ørum-Madsen, Maj S
AU - Gustavsson, Tobias
AU - Dagil, Robert
AU - Daugaard, Mads
AU - Choudhary, Swati
AU - Foged, Camilla
AU - Esko, Jeffrey D
AU - Zhang, Liangfang
AU - Fang, Ronnie H
AU - Salanti, Ali
PY - 2023
Y1 - 2023
N2 - Malaria infected erythrocytes utilize the parasite protein VAR2CSA to bind to a unique presentation of chondroitin sulfate (CS) for their placenta specific tropism. Interestingly, many cancers express a similar form of CS, thereby termed oncofetal CS (ofCS). The distinctive tropism of malaria infected erythrocytes and the identification of oncofetal CS, therefore, represent potentially potent tools for cancer targeting. Here we describe an intriguing drug delivery platform that effectively mimics infected erythrocytes and their specificity for ofCS. We used a lipid catcher-tag conjugation system for the functionalization of erythrocyte membrane-coated drug carriers with recombinant VAR2CSA (rVAR2). We show that these malaria mimicking erythrocyte nanoparticles (MMENPs) loaded with docetaxel (DTX) specifically target and kill melanoma cells in vitro. We further demonstrate effective targeting and therapeutic efficacy in a xenografted melanoma model. These data thus provide a proof of concept for the use of a malaria biomimetic for tumor targeted drug delivery. Given the broad presentation of ofCS found across various types of malignancies, this biomimetic may therefore show potential as a broadly targeted cancer therapy against multiple tumor indications.
AB - Malaria infected erythrocytes utilize the parasite protein VAR2CSA to bind to a unique presentation of chondroitin sulfate (CS) for their placenta specific tropism. Interestingly, many cancers express a similar form of CS, thereby termed oncofetal CS (ofCS). The distinctive tropism of malaria infected erythrocytes and the identification of oncofetal CS, therefore, represent potentially potent tools for cancer targeting. Here we describe an intriguing drug delivery platform that effectively mimics infected erythrocytes and their specificity for ofCS. We used a lipid catcher-tag conjugation system for the functionalization of erythrocyte membrane-coated drug carriers with recombinant VAR2CSA (rVAR2). We show that these malaria mimicking erythrocyte nanoparticles (MMENPs) loaded with docetaxel (DTX) specifically target and kill melanoma cells in vitro. We further demonstrate effective targeting and therapeutic efficacy in a xenografted melanoma model. These data thus provide a proof of concept for the use of a malaria biomimetic for tumor targeted drug delivery. Given the broad presentation of ofCS found across various types of malignancies, this biomimetic may therefore show potential as a broadly targeted cancer therapy against multiple tumor indications.
U2 - 10.1021/acsnano.3c01910
DO - 10.1021/acsnano.3c01910
M3 - Journal article
C2 - 37435892
VL - 17
SP - 13500
EP - 13509
JO - A C S Nano
JF - A C S Nano
SN - 1936-0851
IS - 14
ER -
ID: 359186611