Biomimicking Platelet-Monocyte Interactions as a Novel Targeting Strategy for Heart Healing
Bill Cheng1, Elsie K W Toh1, Kun-Hung Chen1
1Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang District Taipei, 115, Taiwan.
Insights
New platelet-like proteoliposomes (PLPs) target monocytes in the heart after myocardial infarction, offering improved drug delivery for congestive heart failure (CHF) therapy. This approach bypasses the limited enhanced permeability and retention (EPR) effect for better cardioprotection.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Drug Delivery Systems
Background:
- Congestive heart failure (CHF) is a common complication after myocardial infarction (MI).
- Current cardioprotective drug delivery relies on the transient enhanced permeability and retention (EPR) effect, which is insufficient for post-MI therapy.
- Monocyte recruitment to the injured heart post-MI presents a therapeutic target.
Purpose of the Study:
- To develop a novel drug delivery system, platelet-like proteoliposomes (PLPs), to target monocytes in the heart post-MI.
- To investigate the efficacy of PLPs in delivering anti-inflammatory drugs independently of the EPR effect.
- To improve therapeutic outcomes for post-infarction heart failure.
Main Methods:
- Development of PLPs designed to mimic platelet-monocyte interactions.
- In vitro assessment of PLP binding affinity to monocytes and endothelial cells.
- Intravital multiphoton imaging to track PLP accumulation at the infarction site post-MI.
- Evaluation of PLP-mediated delivery of cobalt protoporphyrin for therapeutic effect.
Main Results:
- PLPs demonstrated specific binding to monocytes and not endothelial cells in vitro.
- PLPs accumulated at the infarction site 72 hours post-MI, unlike plain liposomes.
- PLP-mediated drug delivery enhanced targeting to the heart in an EPR-independent manner.
- Improved therapeutic outcomes were observed with PLP-delivered anti-inflammatory drugs.
Conclusions:
- Platelet-like proteoliposomes offer a promising strategy for targeted drug delivery to the heart post-myocardial infarction.
- This novel approach overcomes the limitations of the EPR effect for enhanced cardioprotection.
- PLPs represent a potential breakthrough in treating post-infarction congestive heart failure.
Abstract:
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.
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