Biomimicking Platelet-Monocyte Interactions as a Novel Targeting Strategy for Heart Healing.
In patients who survive myocardial infarction, many go on to develop congestive heart failure (CHF). Despite ongoing efforts to develop new approaches for postinfarction therapy, there are still no effective therapeutic options available to CHF patients. Currently, the delivery of cardioprotective drugs relies entirely on passive uptake via the enhanced permeability and retention (EPR) effect which occurs in proximity to the infarction site. However, in ischemic disease, unlike in cancer, the EPR effect only exists for a short duration postinfarction and thus insufficient for meaningful cardioprotection. Splenic monocytes are recruited to the heart in large numbers postinfarction, and are known to interact with platelets during circulation. Therefore, the strategy is to exploit this interaction by developing platelet-like proteoliposomes (PLPs), biomimicking platelet interactions with circulating monocytes. PLPs show strong binding affinity for monocytes but not for endothelial cells in vitro, mimicking normal platelet activity. Furthermore, intravital multiphoton imaging shows that comparing to plain liposomes, PLPs do not aggregate on uninjured endothelium but do accumulate at the injury site 72 h postinfarction. Importantly, PLPs enhance the targeting of anti-inflammatory drug, cobalt protoporphyrin, to the heart in an EPR-independent manner, which result in better therapeutic outcome.
Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang District Taipei, 115, Taiwan.
Bill
B
Cheng
Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang District Taipei, 115, Taiwan.
Elsie K W
EK
Toh
Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang District Taipei, 115, Taiwan.
Kun-Hung
KH
Chen
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan.
Yuan-Chih
YC
Chang
Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang District Taipei, 115, Taiwan.
Che-Ming J
CJ
Hu
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan.
Han-Chung
HC
Wu
Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang District Taipei, 115, Taiwan.
Lee-Young
LY
Chau
Research Center for Applied Sciences, Academia Sinica, Taipei, 115, Taiwan.
Peilin
P
Chen
Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang District Taipei, 115, Taiwan. phsieh@ibms.sinica.edu.tw.
Patrick C H
PC
Hsieh
D000818:Animals; D040761:Biomimetic Materials / Q000008:administration & dosage* / Q000737:chemistry; D001792:Blood Platelets / Q000737:chemistry*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000737:chemistry; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008081:Liposomes / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects*; D009203:Myocardial Infarction / Q000628:therapy*; D010539:Permeability; D015539:Platelet Activation / Q000187:drug effects; D000067996:RAW 264.7 Cells; D014945:Wound Healing / Q000187:drug effects*
D002316:Cardiotonic Agents; D008081:Liposomes
biomimicry; cardioprotection; monocytes; myocardial infarction; nanomedicines