Escape sites from the endo-lysosomal trafficking route manipulate exocytosis of nanoparticles in polar epithelium.

The endo-lysosomal pathway is a major barrier for the trans-epithelial transport of nanoparticles (NPs), but escape strategies could facilitate trans-epithelial delivery. Based on the polarization properties of the epithelium, different escape compartments may result in different exocytosis fates of NPs and further affect the delivery efficiency. Therefore, optimizing the escape sites is critical for trans-epithelial delivery. Here, commonly used PEG-coated-poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles were fabricated as model nanoparticles (MNPs) and the intestinal epithelium was chosen as the polarized epithelium. The MNPs were incubated with different endosomolytic agents for early endosomal escape, late endosomal escape and lysosomal escape, respectively. According to in vitro and in vivo studies, MNPs escaping from early endosomes and late endosomes exhibited stronger capacity for trans-epithelial transport than those escaping from lysosomes. By further probing into the mechanism, we surprisingly found that although MNPs escaping from early endosomes quickly egressed from the apical side of epithelia, they were subsequently followed by "reuptake" via caveolae and trafficked through the endoplasmic reticulum-Golgi apparatus (ER/GA) secretory pathway, achieving efficient trans-epithelial transport; MNPs escaping from late endosomes, which were located near the nucleus, were prone to enter the ER/GA for efficient basolateral exocytosis. However, MNPs escaping from lysosomes were detained within cells by autophagosomes. Collectively, our research suggested that early endosomes and late endosomes were ideal escape sites for trans-epithelial delivery.

Enhanced oral and pulmonary delivery of biomacromolecules via amplified transporter targeting.

Ligand-modified nanocarriers can promote oral or inhalative administration of macromolecular drugs across the intestinal or pulmonary mucosa. However, enhancing the unidirectional transport of the nanocarriers through "apical uptake→intracellular transport→basolateral exocytosis" route remains a hot topic and challenge in current research. Forskolin is a naturally occurring diterpenoid compound extracted from the roots of C. forskohlii. In our studies, we found that forskolin could increase the transcellular transport of butyrate-modified nanoparticles by 1.67-fold and 1.20-fold in Caco-2 intestinal epithelial cell models and Calu-3 lung epithelial cell models, respectively. Further mechanistic studies revealed that forskolin, on the one hand, promoted the cellular uptake of butyrate-modified nanoparticles by upregulating the expression of monocarboxylic acid transporter-1 (MCT-1) on the apical membrane. On the other hand, forskolin facilitated the binding of MCT-1 to caveolae, thereby mediating butyrate-modified nanoparticles hijacking caveolae to promote the basolateral exocytosis of butyrate-modified nanoparticles. Studies in normal mice model showed that forskolin could promote the transmucosal absorption of butyrate-modified nanoparticles by >2-fold, regardless of oral or inhalative administration. Using semaglutide as the model drug, both oral and inhalation delivery approaches demonstrated significant hypoglycemic effects in type 2 diabetes mice model, in which inhalative administration was more effective than oral administration. This study optimized the strategies aimed at enhancing the transmucosal absorption of ligand-modified nanocarriers in the intestinal or pulmonary mucosa.

Lipoic acid-mediated oral drug delivery system utilizing changes on cell surface thiol expression for the treatment of diabetes and inflammatory diseases.

Lipoic acid (LA), which has good safety and oral absorption, is obtained from various plant-based food sources and needs to be supplemented through human diet. Moreover, substances with a disulfide structure can enter cells through dynamic covalent disulfide exchange with thiol groups on the cell membrane surface. Based on these factors, we constructed LA-modified nanoparticles (LA NPs). Our results showed that LA NPs can be internalized into intestinal epithelial cells through surface thiols, followed by intracellular transcytosis via the endoplasmic reticulum-Golgi pathway. Further mechanistic studies indicated that disulfide bonds within the structure of LA play a critical role in this transport process. In a type I diabetes rat model, the oral administration of insulin-loaded LA NPs exhibited a more potent hypoglycemic effect, with a pharmacokinetic bioavailability of 5.42 ± 0.53%, representing a 1.6 fold enhancement compared to unmodified PEG NPs. Furthermore, a significant upregulation of surface thiols in inflammatory macrophages was reported. Thus, we turned our direction to investigate the uptake behavior of inflammatory macrophages with increased surface thiols towards LA NPs. Inflammatory macrophages showed a 2.6 fold increased uptake of LA NPs compared to non-inflammatory macrophages. Surprisingly, we also discovered that the antioxidant resveratrol facilitates the uptake of LA NPs in a concentration-dependent manner. This is mainly attributed to an increase in glutathione, which is involved in thiol uptake. Consequently, we employed LA NPs loaded with resveratrol for the treatment of colitis and observed a significant alleviation of colitis symptoms. These results suggest that leveraging the variations of thiol expression levels on cell surfaces under both healthy and diseased states through an oral drug delivery system mediated by the small-molecule nutrient LA can be employed for the treatment of diabetes and certain inflammatory diseases.

Sodium-glucose cotransporter 1 promotes the biofunctions of perivascular preadipocytes mediated by Akt/mTOR/p70S6K signaling pathway.

The influence of SGLT-1 on perivascular preadipocytes (PVPACs) and vascular remodeling is not well understood. This study aimed to elucidate the role and mechanism of SGLT-1-mediated PVPACs bioactivity. PVPACs were cultured in vitro and applied ex vivo to the carotid arteries of mice using a lentivirus-based thermosensitive in situ gel (TISG). The groups were treated with Lv-SGLT1 (lentiviral vector, overexpression), Lv-siSGLT1 (RNA interference, knockdown), or specific signaling pathway inhibitors. Assays were conducted to assess changes in cell proliferation, apoptosis, glucose uptake, adipogenic differentiation, and vascular remodeling in the PVPACs. Protein expression was analyzed by Western blotting, immunocytochemistry, and/or immunohistochemistry. The methyl thiazolyl tetrazolium (MTT) assay and Hoechst 33342 staining indicated that SGLT-1 overexpression significantly promoted PVPACs proliferation and inhibited apoptosis in vitro. Conversely, SGLT-1 knockdown exerted the opposite effect. Oil Red O staining revealed that SGLT-1 overexpression facilitated adipogenic differentiation, while its inhibition mitigated these effects. 3H-labeled glucose uptake experiments demonstrated that SGLT-1 overexpression enhanced glucose uptake by PVPACs, whereas RNA interference-mediated SGLT-1 inhibition had no significant effect on glucose uptake. Moreover, RT-qPCR, Western blotting, and immunofluorescence analyses revealed that SGLT-1 overexpression upregulated FABP4 and VEGF-A levels and activated the Akt/mTOR/p70S6K signaling pathway, whereas SGLT-1 knockdown produced the opposite effects. In vivo studies corroborated these findings and indicated that SGLT-1 overexpression facilitated carotid artery remodeling. Our study demonstrates that SGLT-1 activation of the Akt/mTOR/p70S6K signaling pathway promotes PVPACs proliferation, adipogenesis, glucose uptake, glucolipid metabolism, and vascular remodeling.NEW & NOTEWORTHY SGLT-1 is expressed in PVPACs and can affect preadipocyte glucolipid metabolism and vascular remodeling. SGLT-1 promotes the biofunctions of PVPACs mediated by Akt/mTOR/p70S6K signaling pathway. Compared with caudal vein or intraperitoneal injection, the external application of lentivirus-based thermal gel around the carotid artery is an innovative attempt at vascular remodeling model, it may effectively avoid the transfection of lentiviral vector into the whole body of mice and the adverse effect on experimental results.

A Less-is-More Strategy for Mitochondria-Targeted Photodynamic Therapy of Rheumatoid Arthritis.

Conventional photodynamic therapy (PDT) of rheumatoid arthritis (RA) faces a dilemma: low-power is insufficient to kill pro-inflammatory cells while high-power exacerbates inflammation. Herein, mitochondrial targeting is introduced in PDT of RA to implement a "less-is-more" strategy, where higher apoptosis in pro-inflammatory cells are achieved with lower laser power. In arthritic rats, chlorine 6-loaded and mitochondria-targeting liposomes (Ce6@M-Lip) passively accumulated in inflamed joints, entered pro-inflammatory macrophages, and actively localized to mitochondria, leading to enhanced mitochondrial dysfunction under laser irradiation. By effectively disrupting mitochondria, pro-inflammatory macrophages are more susceptible to PDT, resulting in increased apoptosis initiation. Additionally, it identifies that high-power irradiation caused cell rupture and release of endogenous danger signals that recruited and activated additional macrophages. In contrast, under low-power irradiation, mitochondria-targeting Ce6@M-Lip not only prevented inflammation but also reduced pro-inflammatory macrophage infiltration and pro-inflammatory cytokine secretion. Overall, targeting mitochondria reconciled therapeutic efficacy and inflammation, thus enabling efficacious yet inflammation-sparing PDT for RA. This highlights the promise of mitochondrial targeting to resolve the dilemma between anti-inflammatory efficacy and inflammatory exacerbation in PDT by implementing a "less-is-more" strategy.

Exosomal circSCMH1/miR-874 ratio in serum to predict carotid and coronary plaque stability.

Background: To investigate the correlation between lg (circSCMH1/miR-874) and acute coronary syndrome (ACS), acute myocardial infarction (AMI), and carotid plaque stability. Methods: 701 patients were divided into stable coronary artery disease (SCAD), ACS, and control groups. Furthermore, 225 patients who underwent carotid ultrasound were selected from the above 701 patients and were divided into low-risk plaque, medium-to-high risk plaque, and control (without carotid plaques) groups. We collected their baseline characteristics and measured the contents of exosomal circSCMH1 and miR-874 in peripheral blood. Then lg(circSCMH1/miR-874) was calculated and statistical analysis was performed. Results: The lg (circSCMH1/miR-874) values of ACS, SCAD, and the control group decreased successively (P < 0.05). Compared with the low-risk plaque and control groups, the lg (circSCMH1/miR-874) value of medium-high risk plaque group decreased (P < 0.05). Multivariate logistic regression analysis showed that with the decrease of lg (circSCMH1/miR-874), the risk of ACS, AMI, and medium-high risk plaques increased. ROC curve analysis demonstrated that lg (circSCMH1/miR-874) has a higher diagnostic value for ACS, AMI and medium-high risk plaques than previously used predictive ratios. Conclusion: Lg (circSCMH1/miR-874) is closely associated with coronary and carotid plaque stability.

Disease-specific protein corona formed in pathological intestine enhances the oral absorption of nanoparticles.

Protein corona (PC) has been identified to impede the transportation of intravenously injected nanoparticles (NPs) from blood circulation to their targeted sites. However, how intestinal PC (IPC) affects the delivery of orally administered NPs are still needed to be elucidated. Here, we found that IPC exerted "positive effect" or "negative effect" depending on different pathological conditions in the gastrointestinal tract. We prepared polystyrene nanoparticles (PS) adsorbed with different IPC derived from the intestinal tract of healthy, diabetic, and colitis rats (H-IPC@PS, D-IPC@PS, C-IPC@PS). Proteomics analysis revealed that, compared with healthy IPC, the two disease-specific IPC consisted of a higher proportion of proteins that were closely correlated with transepithelial transport across the intestine. Consequently, both D-IPC@PS and C-IPC@PS mainly exploited the recycling endosome and ER-Golgi mediated secretory routes for intracellular trafficking, which increased the transcytosis from the epithelium. Together, disease-specific IPC endowed NPs with higher intestinal absorption. D-IPC@PS posed "positive effect" on intestinal absorption into blood circulation for diabetic therapy. Conversely, C-IPC@PS had "negative effect" on colitis treatment because of unfavorable absorption in the intestine before arriving colon. These results imply that different or even opposite strategies to modulate the disease-specific IPC need to be adopted for oral nanomedicine in the treatment of variable diseases.

Correlation of neck circumference, coronary calcification severity and cardiovascular events in Chinese elderly patients with acute coronary syndromes.

BACKGROUND AND AIMS: We aimed to investigate whether neck circumference (NC) can predict metabolic syndrome (MetS), coronary calcification and lesion, and major adverse cardiovascular events (MACEs). METHODS: A total of 867 patients with acute coronary syndrome (ACS) over 60 years old from the Second Hospital of Shandong University, who had undergone coronary computed tomography, were randomly selected for a retrospective analysis. The subjects were divided into male and female groups, NC quartile 1-4 groups (Q1-Q4 groups), non-multivessel coronary disease (non-MVCD) and multi-vessel coronary disease (MVCD) groups. RESULTS: After adjusting for potential confounders, NC was associated with risk factors promoting coronary artery disease (CAD) and coronary artery calcification score (CACS). The severity of CAD increased by 0.202 times and 0.372 times for each unit of NC in male and female groups, respectively. Compared with the lower CACS group, the risk of coronary calcification increased by 0.139 times, and MVCD increased 0.268 times, with each unit increase of NC. Except for all-cause death, there were significant differences between the Q1-Q4 groups in the prevalence of all primary endpoints, cardiogenic death, unexpected re-hospitalization of heart failure, ACS recurrence or unplanned revascularization, and non-fatal stroke (p log-rank <0.01). In view of the overall trend, with the increase of NC quartiles, the prevalence of MACEs gradually increased (all p < 0.01). CONCLUSIONS: NC is closely associated with MetS and its components, coronary calcification and lesion degree, and MACEs. NC could be used as surrogate of CACS to predict the coronary condition and prognosis of elderly patients with ACS.

Biomimetic nanoparticle synchronizing pyroptosis induction and mitophagy inhibition for anti-tumor therapy.

Inducing pyroptosis in cancer cells can result in a strong anti-tumor immune response. Our preliminary study indicates that pyroptosis can be temporarily strengthened by disrupting mitochondria, but ultimately diminished by defensive mitophagy. Here, this study reports a nano-system camouflaged with hybrid membranes consisting of homologous cell membrane and corresponding mitochondrial membrane, which is used to deliver a drug complex Ca@GOx consisting of calcium phosphate and glucose oxidase. By taking advantage of the homing effects of cell membrane and the orientated fusion mechanism of subcellular membrane, the nano-system is able to deliver Ca@GOx to mitochondria, induce mitochondrial Ca2+ overload and generate significant levels of ROS, thus leading to pyroptosis. However, it's found that this system exhibits limited anti-tumor effects in vivo due to the compensatory activation of mitophagy serving as negative feedback to pyroptosis. To address this issue, mitophagy-inhibiting chloroquine is loaded into nanoparticles to intensify pyroptosis. As a result, the combination significantly promotes tumor infiltration of CD8+T cells and improves anti-tumor effects. Together, this study establishes a rational combination of targeted mitochondria disruption and mitophagy blockage for effective pyroptosis-based therapy.

Milk-derived exosomes as a promising vehicle for oral delivery of hydrophilic biomacromolecule drugs.

Exosomes, as promising vehicles, have been widely used in the research of oral drug delivery, but the generally low drug loading efficiency of exosomes seriously limits its application and transformation. In this study, we systematically investigated the effects of drug loading methods and physicochemical properties (lipophilicity and molecular weight) on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions. Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method, drug lipophilicity, drug molecular weight and exosome/drug proportions. Of note, we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes, which was attributed to the efficient loading capacity and sustained release behavior. Furthermore, milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs (octreotide, exendin-4 and salmon calcitonin). Collectively, our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.

Corrosion and Mechanical Behavior of the As-Cast and Solid-Solution-Treated AM50 Magnesium Alloy in Different Media.

Hydrogen embrittlement and the anodic dissolution mechanism are two important aspects of the corrosion behavior of magnesium alloys. Here, to evaluate the effects of these two aspects on the corrosion failure of magnesium alloys under stress, the stress and corrosion behaviors of the AM50 magnesium alloy in air, deionized water, and NaCl solution after solid-solution (T4) treatment were investigated by X-ray diffraction, scanning electron microscopy, slow strain rate tensile testing, and vacuum dehydrogenation. The as-cast AM50 magnesium alloy was mainly composed of the α-Mg and ß-Mg17Al12 phases. After T4 treatment, the amount of the ß-Mg17Al12 phase was significantly reduced, and only a small amount existed at the grain boundaries. After T4 treatment, the stress corrosion resistance in deionized water improved, but it decreased in an NaCl environment. Dehydrogenation experiments showed that the effect of hydrogen on the corrosion process was weakened owing to the decrease of the ß-Mg17Al12 phase after solution treatment. The effects of hydrogen embrittlement and the anodic dissolution mechanism on the corrosion behavior of the AM50 magnesium alloy under stress were different. In deionized water, the hydrogen embrittlement mechanism played the major role, while the anodic dissolution mechanism played the major role in the presence of Cl- ions.

Mimicking natural cholesterol assimilation to elevate the oral delivery of liraglutide for type II diabetes therapy.

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are a series of polypeptides broadly applied in the long-term treatment of type Ⅱ diabetes. However, administration of GLP-RA is mainly through repetitive subcutaneous injection, which may seriously decrease the compliance and safety. Herein, a bio-inspired oral delivery system was designed to enhance the oral absorption of liraglutide (Lira), a kind of GLP-1 RA, by mimicking the natural cholesterol assimilation. 25-hydroxycholesterol (25HC), a cholesterol derivative, was modified on the surfaced of Lira-loaded PLGA nanoparticles (Lira 25HC NPs) and functioned as a "top-down" actuator to facilitate unidirectional transcytosis across the intestinal epithelium. After oral delivery, Lira 25HC NPs displayed improved therapeutic effect as compared with oral free Lira on type Ⅱ diabetes db/db mice, as evidenced by multiple relieved diabetic symptoms including the enhanced glucose tolerance, repressed weight growth, improved liver glucose metabolism, decreased fasting blood glucose, HbA1c, serum lipid, and increased ß cells activity. Surprisingly, the fasting blood glucose, liver glucose metabolism, and HbA1c of oral Lira-loaded 25HC NPs were comparable to subcutaneous injection of free Lira. Further mechanisms revealed that 25HC ligand could mediate the nanoparticles to mimic natural cholesterol absorption by exerting high affinity towards apical Niemann-Pick C1 Like 1 (NPC1L1) and then basolateral ATP binding cassette transporter A1 (ABCA1) overexpressed on the opposite side of intestinal epithelium. This cholesterol assimilation-mimicking strategy achieve the unidirectional transport across the intestinal epithelium, thus improving the oral absorption of liraglutide. In general, this study established a cholesterol simulated platform and provide promising insight for the oral delivery of GLP-1 RA.

Coordination of rigidity modulation and targeting ligand modification on orally-delivered nanoparticles for the treatment of liver fibrosis.

Although the individual role of ligand modification or rigidity modulation on oral administration of nanoparticle (NP) has been investigated, how they mutually affect each other remains to be elucidated. Here, we fabricated different rigidity NP with or without surface decoration of FcBP, a neonatal Fc receptor domain-binding peptide. In vitro studies showed that, without FcBP modification, stiff NP had higher transcytosis efficiency across the epithelium than softer NP, due to the different endocytosis mechanisms, intracellular trafficking routes, and exocytosis rate. Notably, after FcBP modification, such difference was narrowed, in a manner that was more favorable for softer NP to "catch up" with stiff NP, suggesting ligand modification was more conducive to exert transcytosis-promoting efficacy on softer NP. In vivo experiments demonstrated that, for ligand-free NP, high rigidity was required for efficient oral absorption and liver distribution. Further FcBP modification decreased that "rigidity threshold", and expanded the feasible rigidity range from stiff NP to softer NP. Upon oral administration, FcBP-modified dexamethasone-loaded softer NP achieved a therapeutic efficacy comparable with stiff NP on alleviating liver fibrosis. Collectively, our study highlighted the necessity of coordinating ligand modification and rigidity modulation for oral drug delivery.

Angiopep-2-functionalized nanoparticles enhance transport of protein drugs across intestinal epithelia by self-regulation of targeted receptors.

Ligand-modified nanoparticles (NPs) have been widely used in oral drug delivery systems to promote endocytosis on intestinal epithelia. However, their transcytosis across the intestinal epithelia is still limited. Except for complex intracellular trafficking, recycling again from the apical sides into the intestinal lumen of the endocytosed NPs cannot be ignored. In this study, we modified NP surfaces with angiopep-2 (ANG) that targeted the low-density lipoprotein receptor-related protein 1 (LRP-1) expressed on the intestine to increase both the apical endocytosis and basolateral transcytosis of NPs. Notably, our finding revealed that ANG NPs could increase the apical expression and further basolateral redistribution of LRP-1 on Caco-2 cells, thus generating an apical-to-basolateral absorption pattern. Because of the enhanced transcytosis, insulin loaded ANG NPs possessed much stronger absorption efficiency and induced maximal blood glucose reduction to 61.46% in diabetic rats. Self-regulating the distribution of receptors on polarized intestine cells to promote basolateral transcytosis will provide promising insights for the rational design of oral delivery systems of protein/peptide drugs.

Complying with the physiological functions of Golgi apparatus for secretory exocytosis facilitated oral absorption of protein drugs.

Intestinal epithelial cells are the primary biological barriers for orally administrated nano-formulations and the delivered protein drugs. Thereinto, besides the cellular uptake, intracellular trafficking pathway and the related exocytosis are of great importance to the trans-epithelial transport of drug-loaded NPs. Herein, inspired by the physiological functions of Golgi apparatus for secreting proteins out of cells, Golgi localization-related amino acid l-cysteine (Cys) was modified on the surface of NPs to see whether and how this modification could guide the Golgi pathway-related transport and facilitate the exocytosis of drug-loaded NPs. Meanwhile, cell-penetrating peptide octa-arginine (R8) was co-modified to increase the cellular uptake. The proportion of R8 and Cys modification was explored to get the best effect of endocytosis and exocytosis of NPs. As a result, 25%R8 + 75%Cys NPs with most Cys modification showed efficient transcytosis with the highest transcytosis/endocytosis ratio (0.87). Interestingly, exocytosis mechanism studies indicated that they trafficked through the Golgi secretory pathway and bypassed lysosomes due to Cys modification. The detailed Golgi position mechanism studies further suggested that the thiol group from Cys was important for mediating Golgi transport. In particular, competitive inhibition studies demonstrated that Cys-modified NPs were more conducive to their exocytosis after being transported through the Golgi secretory pathway. We proved that cargos transported via Golgi apparatus tended to be trafficked out of the cells and avoid degradation, which contributed to the transcytosis of 25%R8 + 75%Cys NPs in vitro. Inspiringly, compared with unmodified NPs, 25%R8 + 75%Cys NPs also exhibited promoted intestinal penetration and oral absorption in vivo. Oral delivery of insulin-loaded 25%R8 + 75%Cys NPs showed stronger hypoglycemic effects in diabetic rats. In summary, this work provides a strategy for complying with the physiological functions of Golgi apparatus for secreting to facilitate the exocytosis of NPs, thus further improving the oral absorption of loaded protein drugs.

Tailored elasticity combined with biomimetic surface promotes nanoparticle transcytosis to overcome mucosal epithelial barrier.

Overcoming epithelial barriers to enhance drug absorption is a major challenge for nanoparticle (NP)-based mucosal delivery systems. With adequate physicochemical properties, the transepithelial delivery of NPs may be efficiently enhanced. However, little is known about the role of elasticity on the transport of NPs across the polarized epithelium, especially the processes and mechanisms of endocytosis, intracellular trafficking and exocytosis. In this study, we discovered that zwitterionic hydrogel NPs with varied elasticity displayed considerably different oral insulin absorption on diabetic rats. It was found that NP elasticity strongly shaped the transepithelial behaviors of NPs, and the increase of elasticity boosted the transcytosis by improving both endocytosis and exocytosis. Elasticity also showed a profound effect on the intracellular trafficking routes of NPs, which was closely related to distribution of NPs in exocytosis pathway and their intra-endosome sphere-to-ellipsoid shape transformation. Importantly, NPs with zwitterionic surface experienced more efficient basolateral exocytosis than apical exocytosis, while the elasticity-related exocytosis enhancement appeared to be non-selective. Therefore, tailored elasticity could promote mucosal transcytosis of NPs, which was able to be further improved with biomimetic zwitterionic surface. This study may provide important knowledge for the design of functional nanovehicles to efficiently overcome mucosal epithelial barriers in the future.

[Experimental Study of PMI Foam Composite Properties in Terahertz].

Polymethacrylimide (PMI) foam composite has many excellent properties. Currently, PMI is heat-resistant foam, with the highest strength and stiffness. It is suitable as a high-performance sandwich structure core material. It can replace the honeycomb structure. It is widely used in aerospace, aviation, military, marine, automotive and high-speed trains, etc. But as new sandwich materials, PMI performance testing in the THz band is not yet visible. Based on the Terahertz (THz) time-domain spectroscopy technique, we conducted the transmission and reflection experiments, got the time domain waveforms and power density spectrum. And then we analyzed and compared the signals. The MATALB and Origin 8. 0 was used to calculate and obtain the transmittance (transfer function), absorptivity Coefficient, reflectance and the refractive index of the different thickness Degussa PMI (Model: Rohacell WF71), which were based on the application of the time-domain and frequency-domain analysis methods. We used the data to compared with the THz refractive index and absorption spectra of a domestic PMI, Baoding Meiwo Technology Development Co. , Ltd. (Model: SP1D80-P-30). The result shows that the impact of humidity on the measurement results is obvious. The refractive index of PMI is about 1. 05. The attenuation of power spectrum is due to the signal of the test platform is weak, the sample is thick and the internal scattering of PMI foam microstructure. This conclusion provides a theoretical basis for the THz band applications in the composite PMI. It also made a good groundwork for THz NDT (Non-Destructive Testing, NDT) technology in terms of PMI foam composites.