Biomimetic nanotherapies: red blood cell based core-shell structured nanocomplexes for atherosclerosis management

Cardiovascular disease is the leading cause of mortality worldwide. Atherosclerosis, one of the most common forms of the disease, is characterized by a gradual formation of atherosclerotic plaque, hardening, and narrowing of the arteries. Nanomaterials can serve as powerful delivery platforms for atherosclerosis treatment. However, their therapeutic efficacy is substantially limited in vivo due to nonspecific clearance by the mononuclear phagocytic system. In order to address this limitation, rapamycin (RAP)‐loaded poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles are cloaked with the cell membrane of red blood cells (RBCs), creating superior nanocomplexes with a highly complex functionalized bio‐interface. The resulting biomimetic nanocomplexes exhibit a well‐defined “core–shell” structure with favorable hydrodynamic size and negative surface charge. More importantly, the biomimetic nature of the RBC interface results in less macrophage‐mediated phagocytosis in the blood and enhanced accumulation of nanoparticles in the established atherosclerotic plaques, thereby achieving targeted drug release. The biomimetic nanocomplexes significantly attenuate the progression of atherosclerosis. Additionally, the biomimetic nanotherapy approach also displays favorable safety properties. Overall, this study demonstrates the therapeutic advantages of biomimetic nanotherapy for atherosclerosis treatment, which holds considerable promise as a new generation of drug delivery system for safe and efficient management of atherosclerosis

Macrophage membrane functionalized biomimetic nanoparticles for targeted anti-atherosclerosis applications

Atherosclerosis (AS), the underlying cause of most cardiovascular events, is one of the most common causes of human morbidity and mortality worldwide due to the lack of an efficient strategy for targeted therapy. In this work, we aimed to develop an ideal biomimetic nanoparticle for targeted AS therapy. Methods: Based on macrophage “homing” into atherosclerotic lesions and cell membrane coating nanotechnology, biomimetic nanoparticles (MM/RAPNPs) were fabricated with a macrophage membrane (MM) coating on the surface of rapamycin-loaded poly (lactic-co-glycolic acid) copolymer (PLGA) nanoparticles (RAPNPs). Subsequently, the physical properties of the MM/RAPNPs were characterized. The biocompatibility and biological functions of MM/RAPNPs were determined in vitro. Finally, in AS mouse models, the targeting characteristics, therapeutic efficacy and safety of the MM/RAPNPs were examined. Results: The advanced MM/RAPNPs demonstrated good biocompatibility. Due to the MM coating, the nanoparticles effectively inhibited the phagocytosis by macrophages and targeted activated endothelial cells in vitro. In addition, MM-coated nanoparticles effectively targeted and accumulated in atherosclerotic lesions in vivo. After a 4-week treatment program, MM/RAPNPs were shown to significantly delay the progression of AS. Furthermore, MM/RAPNPs displayed favorable safety performance after long-term administration. Conclusion: These results demonstrate that MM/RAPNPs could efficiently and safely inhibit the progression of AS. These biomimetic nanoparticles may be potential drug delivery systems for safe and effective anti-AS applications

One simple physical embedding technique for the polymer film to be cryoultramicrotomed

AbstractIn order to study the microstructure along the thickness direction of polylactide acid/C60 (PLA/C60) composite film, the sucrose solution was frozen to embed the PLA/C60 composite film at −70°C, and the distribution state of C60 in PLA matrix was observed successfully in the obtained ultrathin sections cryomicrotomed along the thickness direction of the embedded film in the frozen sucrose solution bulk by transmission electron microscope (TEM). Compared with the traditional chemical embedding methods of polymer film using resins such as epoxy and polyester, the newly developed method to embed the PLA/C60 composite film physically with frozen sucrose solution was simple, convenient, efficient, and health friendly

Shape Memory Behavior of Natural <i>Eucommia ulmoides</i> Gum and Low-Density Polyethylene Blends with Two Response Temperatures

A series of shape memory blends of natural Eucommia ulmoides gum (EUG) and low-density polyethylene (LDPE) with a bicontinuous cross-linked structure were prepared by a physical blending method, which could be used in the field of thermal response with two different temperatures. We report the shape memory properties of these blended materials with two response temperatures for the first time. The mechanical, curing, thermal and shape memory properties of the blends were studied in this manuscript. Schematic diagrams are proposed to illustrate the dual shape memory behaviors of the EUG/LDPE blends. Our study focused on observing the relationship between the shape memory behavior and the microscopic crystalline phase states in the blends. In the blends, both the cross-linked network and the LDPE crystalline regions could act as fixed domains, while the crystalline regions of LDPE or EUG could act as the reversible domain. The shape memory properties were mainly determined by the components of the fixed and reversible domains. We focused on the shape memory behavior of blends at 60 &#176;C and 130 &#176;C in this manuscript. The results showed that when the peroxide dicumyl peroxide (DCP) dosage was 1.0 phr, the blends exhibited acceptable shape behavior at 60 &#176;C (R1f = 74.8%, R1r = 63.3%). At the same time, when DCP dosage was 0.4 phr, the shape memory behavior of the blends at 130 &#176;C was good and much better than that at 60 &#176;C (R2f = 91.1%, R2r = 89.4%)

Shape Memory Behavior of Carbon Black-reinforced Trans-1,4-polyisoprene and Low-density Polyethylene Composites

Shape memory composites of trans-1,4-polyisoprene (TPI) and low-density polyethylene (LDPE) with easily achievable transition temperatures were prepared by a simple physical blending method. Carbon black (CB) was introduced to improve the mechanical properties of the TPI/LDPE composites. The mechanical, cure, thermal and shape memory properties of the TPI/LDPE/CB composites were investigated in this study. In these composites, the crosslinked network generated in both the TPI and LDPE portions acted as a fixed domain, while the crystalline regions of the TPI and LDPE portions acted as a reversible domain in shape memory behavior. We found the mechanical properties of composites were promoted significantly with an increase of CB content, accompanied with the deterioration of shape memory properties of composites. When CB dosage was 5 parts per hundred of rubber composites (phr), best shape memory property of composites was obtained with a shape fixity ratio of 95.1% and a shape recovery ratio of 95.0%

Oscillatory shear stress-induced downregulation of TET1s injures vascular endothelial planar cell polarity by suppression of actin polymerization

Vascular endothelial polarity induced by blood flow plays crucial roles in the development of atherosclerosis. Loss of endothelial polarity leads to an increase in permeability and leukocyte recruitment, which are crucial hallmarks of atherosclerotic initiation. Endothelial cells exhibit a morphological adaptation to hemodynamic shear stress and possesses planar cell polarity to the direction of blood flow. However, the mechanism of how hemodynamic shear stress regulates endothelial planar cell polarity has not been firmly established. Here, we found that TET1s, a short isoform of Tet methylcytosine dioxygenase 1, was a mediator in the regulation of the planar cell polarity in endothelial cells in response to hemodynamic shear stress. In the process, low expression of TET1s induced by oscillatory shear stress led to the endothelial planar polarity damage through inhibition of F-actin polymerization. TET1s can regulate demethylation level of the sFRP-1 promoter to alter the expression of sFRP-1, which affects the interaction of sFRP-1/Fzd4 and F-actin polymerization. Our study revealed the mechanism of how TET1s mediates endothelial planar cell polarity in response to hemodynamic shear stress and provides a new insight for the prevention of atherosclerosis

Biomechanical regulation of vascular smooth muscle cell functions:from in vitro to in vivo understanding

Vascular smooth muscle cells (VSMCs) have critical functions in vascular diseases. Haemodynamic factors are important regulators of VSMC functions in vascular pathophysiology. VSMCs are physiologically active in the three-dimensional matrix and interact with the shear stress sensor of endothelial cells (ECs). The purpose of this review is to illustrate how haemodynamic factors regulate VSMC functions under two-dimensional conditions in vitro or three-dimensional co-culture conditions in vivo. Recent advances show that high shear stress induces VSMC apoptosis through endothelial-released nitric oxide and low shear stress upregulates VSMC proliferation and migration through platelet-derived growth factor released by ECs. This differential regulation emphasizes the need to construct more actual environments for future research on vascular diseases (such as atherosclerosis and hypertension) and cardiovascular tissue engineering