Targeted delivery of fat extract by platelet membrane-cloaked nanocarriers for the treatment of ischemic stroke

Abstract

Background Our previous studies suggest that human fat extract (FE) contains a variety of angiogenic factors and may provide an alternative treatment option for stroke. However, the therapeutic effect is largely limited due to its short half-life, and inaccurate targeting. Results Herein, we leverage the targeting abilities of platelets (PLTs) to the lesion area of stroke and Arg-Gly-Asp (RGD) peptides to the angiogenic blood vessels to develop a biomimetic nanocarrier that capable of delivering FE precisely to treat stroke. The biomimetic nanocarriers are comprised of FE-encapsulated PLGA (poly(lactic-co-glycolic acid)) core enclosed by RGD peptides decorated plasma membrane of PLTs, namely RGD-PLT@PLGA-FE. We found that RGD-PLT@PLGA-FE not only targeted damaged and inflamed blood vessels but also achieved rapid accumulation in the lesion area of ischemic brain. In addition, RGD-PLT@PLGA-FE kept a sustained release behavior of FE at the lesion site, effectively increased its half-life and promoted angiogenesis and neurogenesis with delivering neurotrophic factors including BDNF, GDNF and bFGF to the brain, that ultimately resulted in blood flow increase and neurobehavioral recovery. Conclusions In conclusion, our study provides a new strategy to design a biomimetic system for FE delivery and it is a promising modality for stroke therapy. Graphical Abstract

Platelet Membrane–Encapsulated MSNs Loaded with SS31 Peptide Alleviate Myocardial Ischemia-Reperfusion Injury

“…In the process of MI/RI, vascular damage and exposure of subendothelial matrix components, such as collagen and von Willebrand factor (vWF) can cause platelet aggregation to the injury site. At the same time, glycoproteins on the platelet surface, such as GPVI, GPIV, GPIb, GPIX, GPV, and GPIIb/IIIa, are also involved in platelet aggregation [ 44 ]. Therefore, the function of targeting the damaged cardiovascular site can be achieved through the encapsulation of the platelet membrane.…”

Cell-Membrane-Coated Nanoparticles for Targeted Drug Delivery to the Brain for the Treatment of Neurological Diseases

“…Based on the close interaction between platelets and strokes, there have been many studies to design stroke-targeted drug delivery systems ( Figure 2 ) [ 67 , 69 , 73 ]. For example, Wang C. et al recently designed a new type of PCMCNP: RGD-PLT@PLGA-FE [ 73 ].…”

“…Based on the close interaction between platelets and strokes, there have been many studies to design stroke-targeted drug delivery systems ( Figure 2 ) [ 67 , 69 , 73 ]. For example, Wang C. et al recently designed a new type of PCMCNP: RGD-PLT@PLGA-FE [ 73 ]. Fat extract (FE) has been shown to be effective in treating IS, but its short half-life and inability to cross the BBB limit its use [ 74 ].…”

“…Subsequently, the production and release of NO at the lesion site increased, which promoted vasodilation and disrupted local PLT aggregation to delay the progression of thrombotic plaques [ 67 ]. In another study, platelet membranes were again used to coat the nanocarriers [ 73 ]. However, this PLT-membrane-cloaked nanocarrier delivered human FE to the infarct area of the stroke [ 73 ].…”

Harnessing nanobiotechnology for cerebral ischemic stroke management

“…Encouragingly, PLGA-mediated drug delivery platforms have a good performance in solving BBB-related problems, according to recent research. 62,63…”