Bergamot essential oil improves CUMS-induced depression-like behaviour in rats by protecting the plasticity of hippocampal neurons.

Bergamot essential oil (BEO) is an extract of the bergamot fruit with significant neuroprotective effect. This study was to investigate the effects and the underlying mechanism of BEO in mitigating depression. GC-MS were used to identify its constituents. Antidepressive properties of BEO were evaluated by sucrose preference test (SPT), force swimming test (FST) and open field test (OFT). Nissl staining was used to determine the number of Nissl bodies in hippocampus (HIPP) of rats. Changes in HIPP dendritic length and dendritic spine density were detected by Golgi-Cox staining. Immunohistochemistry and Western blot were used to detect the postsynaptic density protein-95 (PSD-95) and synaptophysin (SYP) in the HIPP of rats. The enzyme-linked immunosorbent assay was used to determine the 5-hydroxytryptamine (5-HT), insulin-like growth factor 1 (IGF-1) and interleukin-1ß (IL-1ß) in the HIPP, serum and cerebrospinal fluid (CSF) of rats. Inhaled BEO significantly improved depressive behaviour in chronic unpredictable mild stress (CUMS) rats. BEO increased Nissl bodies, dendritic length and spine density, PSD-95 and SYP protein in the HIPP. Additionally, BEO upregulated serum 5-HT, serum and CSF IGF-1, while downregulating serum IL-1ß. Collectively, inhaled BEO mitigates depression by protecting the plasticity of hippocampal neurons, hence, providing novel insights into treatment of depression.

Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats.

BACKGROUND: Chronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH. METHODS: This study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin-angiotensin-aldosterone system (RAAS), and characterize alterations in the serum metabolic profile. RESULTS: At 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group. CONCLUSIONS: Our findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances.

Autophagy in dry AMD: A promising therapeutic strategy for retinal pigment epithelial cell damage.

Dry age-related macular degeneration (AMD) is a prevalent clinical condition that leads to permanent damage to central vision and poses a significant threat to patients' visual health. Although the pathogenesis of dry AMD remains unclear, there is consensus on the role of retinal pigment epithelium (RPE) damage. Oxidative stress and chronic inflammation are major contributors to RPE cell damage, and the NOD-like receptor thermoprotein structural domain-associated protein 3 (NLRP3) inflammasome mediates the inflammatory response leading to apoptosis in RPE cells. Furthermore, lipofuscin accumulation results in oxidative stress, NLRP3 activation, and the development of vitelliform lesions, a hallmark of dry AMD, all of which may contribute to RPE dysfunction. The process of autophagy, involving the encapsulation, recognition, and transport of accumulated proteins and dead cells to the lysosome for degradation, is recognized as a significant pathway for cellular self-protection and homeostasis maintenance. Recently, RPE cell autophagy has been discovered to be closely linked to the development of macular degeneration, positioning autophagy as a cutting-edge research area in the realm of dry AMD. In this review, we present an overview of how lipofuscin, oxidative stress, and the NLRP3 inflammasome damage the RPE through their respective causal mechanisms. We summarized the connection between autophagy, oxidative stress, and NLRP3 inflammatory cytokines. Our findings suggest that targeting autophagy improves RPE function and sustains visual health, offering new perspectives for understanding the pathogenesis and clinical management of dry AMD.

Aloperine protects pulmonary hypertension via triggering PPARγ signaling and inhibiting calcium regulatory pathway in pulmonary arterial smooth muscle cells.

Previous studies have reported the beneficial role of Aloperine (ALO), an active vasodilator purified from the seeds and leaves of the herbal plant Sophora alopecuroides L., on experimental pulmonary hypertension (PH); however, detailed mechanisms remain unclear. In this study, monocrotaline-induced PH (MCT-PH) rat model and primarily cultured rat distal pulmonary arterial smooth muscle cells (PASMCs) were used to investigate the mechanisms of ALO on experimental PH, pulmonary vascular remodeling, and excessive proliferation of PASMCs. Results showed that first, ALO significantly prevented the disease development of MCT-PH by inhibiting right ventricular systolic pressure (RVSP) and right ventricular hypertrophy indexed by the Fulton Index, normalizing the pulmonary arterials (PAs) remodeling and improving the right ventricular function indexed by transthoracic echocardiography. ALO inhibited the excessive proliferation of both PAs and PASMCs. Then, isometric tension measurements showed vasodilation of ALO on precontracted PAs isolated from both control and MCT-PH rats via activating the KCNQ channel, which was blocked by specific KCNQ potassium channel inhibitor linopirdine. Moreover, by using immunofluorescence staining and nuclear/cytosol fractionation, we further observed that ALO significantly enhanced the PPARγ nuclear translocation and activation in PASMCs. Transcriptome analyses also revealed activated PPARγ signaling and suppressed calcium regulatory pathway in lungs from MCT-PH rats treated with ALO. In summary, ALO could attenuate MCT-PH through both transient vasodilation of PAs and chronic activation of PPARγ signaling pathway, which exerted antiproliferative roles on PASMCs and remodeled PAs.NEW & NOTEWORTHY Aloperine attenuates monocrotaline-induced pulmonary hypertension (MCT-PH) in rats by inhibiting the pulmonary vascular remodeling and proliferation of pulmonary arterial smooth muscle cells (PASMCs). In mechanism, Aloperine not only exerts a transient KCNQ-dependent vasodilation in precontracted pulmonary arteries (PAs) from both control and MCT-PH rats but also activates PPARγ nuclear translocation and signaling transduction in PASMCs, which chronically inhibits the calcium regulatory pathway and proliferation of PASMCs.

Thermosensitive PNIPAM-Based Hydrogel Crosslinked by Composite Nanoparticles as Rapid Wound-Healing Dressings.

Chronic wounds are prone to produce excessive reactive oxygen species (ROS), which are the main reason for multiple bacterial infections and ulcers at the wound. Therefore, regulating ROS is the key in the process of wound healing. Herein, a new type of thermosensitive hydrogels is developed to improve the scavenging efficiency of ROS and accelerate wound repair. Nano-CeO2 was uniformly dispersed on the surface of mesoporous silica (MSN). The nanocomposite particles were physically crosslinked with poly(N-isopropylacrylamide) (PNIPAM) to form a MSN-CeO2@PNIPAM thermoresponsive hydrogel (PMCTH). The stability, temperature sensitivity, rheological properties, biocompatibility, and wound healing ability of the PMCTH were evaluated in detail. The results showed that the hydrogel could not only maintain the stability of the system for a long time with low biological toxicity but also have a phase transition temperature close to the human body temperature. In addition, the PMCTH was directly applied onto the skin surface. The MSN-CeO2 nanoparticles would be dispersed in the hydrogel to restrict ROS exacerbation effects and promoted the formation of blood vessels as well as surrounding tissues, accelerating the wound healing. More importantly, animal experiments showed that when the mass ratio of CeO2 to MSN was 40%, the wound healing rate reached up to 78% on the 10th day, which was far higher than that of other experimental groups. This study provides a new strategy and experimental basis for the applications of functional hydrogels in wound repair.

Active ingredients of Chinese medicine with immunomodulatory properties: NF-κB pathway and Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease with a complex pathogenesis and no cure. Persistent neuroinflammation plays an important role in the development of PD, and activation of microglia and astrocytes within the central nervous system leads to an inflammatory response and production of pro-inflammatory factors, and activation of NF-κB is key to neuroglial activation in chronic inflammation in PD and a hallmark of the onset of neuroinflammatory disease. Therefore, inhibiting NF-κB activation to prevent further loss of dopaminergic nerves is a more effective means of treating PD. It has been found that an increasing number of active ingredients in Chinese medicines, such as flavonoids, alkaloids, saponins, terpenoids, phenols and phenylpropanoids, have anti-inflammatory properties that can regulate neuroglia cell activation and ameliorate neuroinflammation through the NF-κB pathway, and increase dopamine release or protect dopaminergic neurons for neuroprotection to improve behavioural dysfunction in PD. The active ingredients of traditional Chinese medicine are expected to be good candidates for the treatment of PD, as they provide holistic regulation through multi-targeting and multi-level effects, and are safe, inexpensive and readily available. Therefore, this paper summarises that the active ingredients of some relevant Chinese medicines ameliorate the symptoms of PD and delay the development of PD by inhibiting glial cell-mediated neuroinflammation through the NF-κB pathway, which may provide new ideas for exploring the molecular mechanism of PD pathogenesis and developing new anti-PD drugs.

Retinal light damage: From mechanisms to protective strategies.

Visible light serves as a crucial medium for vision formation.;however, prolonged or excessive exposure to light is recognized as a significant etiological factor contributing to retinal degenerative diseases. The retina, with its unique structure and adaptability, relies on the homeostasis of cellular functions to maintain visual health. Under normal conditions, the retina can mount adaptive responses to various insults, including light-induced damage. Unfortunately, exposure to intense and excessive light triggers a cascade of pathological alterations in retinal photoreceptor cells, pigment epithelial cells, ganglion cells, and glial cells. These alterations encompass disruption of intracellular REDOX and Ca²âº homeostasis, pyroptosis, endoplasmic reticulum stress, autophagy, and the release of inflammatory cytokines, culminating in irreversible retinal damage. We first delineate the mechanisms of retinal light damage through 4 main avenues: mitochondria function, endoplasmic reticulum stress, cell autophagy, and inflammation. Subsequently, we discuss protective strategies against retinal light damage, aiming to guide research toward the prevention and treatment of light-induced retinal conditions.

Pro-inflammatory cytokines in stress-induced depression: Novel insights into mechanisms and promising therapeutic strategies.

Stress-mediated depression is one of the common psychiatric disorders with a high prevalence and suicide rate, there is a lack of effective treatment. Accordingly, effective treatments with few adverse effects are urgently needed. Pro-inflammatory cytokines (PICs) may play a key role in stress-mediated depression. Thereupon, both preclinical and clinical studies have found higher levels of IL-1ß, TNF-α and IL-6 in peripheral blood and brain tissue of patients with depression. Recent studies have found PICs cause depression by affecting neuroinflammation, monoamine neurotransmitters, hypothalamic pituitary adrenal axis and neuroplasticity. Moreover, they play an important role in the symptom, development and progression of depression, maybe a potential diagnostic and therapeutic marker of depression. In addition, well-established antidepressant therapies have some relief on high levels of PICs. Importantly, anti-inflammatory drugs relieve depressive symptoms by reducing levels of PICs. Collectively, reducing PICs may represent a promising therapeutic strategy for depression.

Immunomodulation: The next target of mesenchymal stem cell-derived exosomes in the context of ischemic stroke.

Ischemic stroke (IS) is the most prevalent form of brain disease, characterized by high morbidity, disability, and mortality. However, there is still a lack of ideal prevention and treatment measures in clinical practice. Notably, the transplantation therapy of mesenchymal stem cells (MSCs) has been a hot research topic in stroke. Nevertheless, there are risks associated with this cell therapy, including tumor formation, coagulation dysfunction, and vascular occlusion. Also, a growing number of studies suggest that the therapeutic effect after transplantation of MSCs is mainly attributed to MSC-derived exosomes (MSC-Exos). And this cell-free mediated therapy appears to circumvent many risks and difficulties when compared to cell therapy, and it may be the most promising new strategy for treating stroke as stem cell replacement therapy. Studies suggest that suppressing inflammation via modulation of the immune response is an additional treatment option for IS. Intriguingly, MSC-Exos mediates the inflammatory immune response following IS by modulating the central nervous system, the peripheral immune system, and immunomodulatory molecules, thereby promoting neurofunctional recovery after stroke. Thus, this paper reviews the role, potential mechanisms, and therapeutic potential of MSC-Exos in post-IS inflammation in order to identify new research targets.

SARS-CoV-2 spike protein receptor-binding domain perturbates intracellular calcium homeostasis and impairs pulmonary vascular endothelial cells.

Exposure to the spike protein or receptor-binding domain (S-RBD) of SARS-CoV-2 significantly influences endothelial cells and induces pulmonary vascular endotheliopathy. In this study, angiotensin-converting enzyme 2 humanized inbred (hACE2 Tg) mice and cultured pulmonary vascular endothelial cells were used to investigate how spike protein/S-RBD impacts pulmonary vascular endothelium. Results show that S-RBD leads to acute-to-prolonged induction of the intracellular free calcium concentration ([Ca2+]i) via acute activation of TRPV4, and prolonged upregulation of mechanosensitive channel Piezo1 and store-operated calcium channel (SOCC) key component Orai1 in cultured human pulmonary arterial endothelial cells (PAECs). In mechanism, S-RBD interacts with ACE2 to induce formation of clusters involving Orai1, Piezo1 and TRPC1, facilitate the channel activation of Piezo1 and SOCC, and lead to elevated apoptosis. These effects are blocked by Kobophenol A, which inhibits the binding between S-RBD and ACE2, or intracellular calcium chelator, BAPTA-AM. Blockade of Piezo1 and SOCC by GsMTx4 effectively protects the S-RBD-induced pulmonary microvascular endothelial damage in hACE2 Tg mice via normalizing the elevated [Ca2+]i. Comparing to prototypic strain, Omicron variants (BA.5.2 and XBB) of S-RBD induces significantly less severe cell apoptosis. Transcriptomic analysis indicates that prototypic S-RBD confers more severe acute impacts than Delta or Lambda S-RBD. In summary, this study provides compelling evidence that S-RBD could induce persistent pulmonary vascular endothelial damage by binding to ACE2 and triggering [Ca2+]i through upregulation of Piezo1 and Orai1. Targeted inhibition of ACE2-Piezo1/SOCC-[Ca2+]i axis proves a powerful strategy to treat S-RBD-induced pulmonary vascular diseases.

Microglia: The Hub of Intercellular Communication in Ischemic Stroke.

Communication between microglia and other cells has recently been at the forefront of research in central nervous system (CNS) disease. In this review, we provide an overview of the neuroinflammation mediated by microglia, highlight recent studies of crosstalk between microglia and CNS resident and infiltrating cells in the context of ischemic stroke (IS), and discuss how these interactions affect the course of IS. The in-depth exploration of microglia-intercellular communication will be beneficial for therapeutic tools development and clinical translation for stroke control.

Quantitative analysis of hemoglobin content in polymeric nanoparticles as blood substitutes using Fourier transform infrared spectroscopy.

Based on the penetrability of IR within the polymeric nanoparticles, a novel Fourier transform infrared spectroscopy (FTIR) method, with polyacrylonitrile (PAN) as the internal reference standard, was developed to quantify the hemoglobin (Hb) content in Hb-based polymeric nanoparticles (HbPN). The HbPN was fabricated by double emulsion method from poly(ethylene glycol)-poly(lactic acid)-poly(ethylene glycol) triblock copolymers. Depending on the characteristic un-overlapped IR absorbances at 1540 cm(-1) of Hb (amide II) and at 2241 cm(-1) of PAN(-C[triple bond]N), calibration equations, presenting the peak height ratio of Hb and PAN as a function of the weight ratio of Hb and PAN, were established. This new quantification method is validated and used to the determination Hb content in HbPN. Due to the good results of this calibration strategy, the proposed simple FTIR approach with minimal sample-needed and solvent-free makes it useful for routine analysis of protein content and could be also applied to any other drug/protein encapsulated particles.

Study of pH-Responsive and Polyethylene Glycol-Modified Doxorubicin-Loaded Mesoporous Silica Nanoparticles for Drug Delivery.

Tumor-targeted drug delivery systems represent challenging and widely investigated strategies to enhance cancer chemotherapy. In this study, we introduce a novel high-hydrophilic mesoporous silica nanoparticle system with a pH-sensitive drug release. The resultant composite nanoparticles appear as spheres of uniform size (450±25 nm) with a porous structure, which enables a high drug-loading ratio. Through modification of chitosan and polyethylene glycol monomethyl ether, the modified mesoporous silica was non-toxic to normal cells, but effective at inducing tumor cell death. With regard to the characteristics of drug release, the modified mesoporous silica clearly displayed a pH-stimulated release of the model drug doxorubicin hydrochloride in an acidic phosphate buffer solution (pH 4.0 and 6.0). The release was much greater than that observed in neutral or alkaline phosphate buffer solutions (pH 7.3 and 8.0). Furthermore, the release behavior was in accordance with the Higuchi model, indicating that this modified mesoporous silica drug delivery system can exhibit controlled release. The above results imply that the modified mesoporous silica is an effective drug delivery system for cancer therapy.

Influence of PEG chain on the complement activation suppression and longevity in vivo prolongation of the PCL biomedical nanoparticles.

The process of opsonization is the major biological barrier to the injectable polymeric nanoparticles (NPs). Complement protein is one kind of opsonins and it can be activated potentially by the negative charged particles. The fragment C3b generated by complement activation could subsequently induce the opsonization on the NPs surface. The aim of our work was to examine the relationship between the hydrophilic poly(ethylene glycol) (PEG) chain on the surface of NPs and particles longevity in vivo from the biological point of view such as complement activation (C3 cleavage) as well as uptake by macrophages. The studies showed that the introduction of PEG chains led to slightly smaller NPs with lower polydispersities than those prepared from naked poly(epsilon-caprolactone) (PCL) and enhanced the zeta potential of NPs from -27.17 mV to -6.046 mV. It was also found that PEG hydrophilic chain could decrease the C3 cleavage and remarkably suppress opsonization and phagocytosis subsequently. In biodistribution investigations in vivo, as a control, PCL NPs were present in MPS tissues in the first 5 min followed by metabolism elimination rapidly, whereas the PEGylated NPs had more particles blood retention in vivo after injection. In fact, in present work, it has been convinced that these results in vivo could be predicted by the in vitro fluorescent phagocytosis model and the extent of complement activation in advance.

A noninvasive method for measuring the oxygen binding-releasing capacity of hemoglobin-loaded polymeric nanoparticles as oxygen carrier.

Based on the strong penetration capacity of near infrared lights (NIRs) and different absorption of oxyhemoglobin and deoxyhemoglobin in NIRs region, a novel noninvasive method, with the aid of an airproof-equilibrium apparatus, was developed to determine the oxygen binding-releasing capacity, including oxygen dissociation curve (ODC) and P(50), of the hemoglobin-loaded polymeric nanoparticles (HbP) in this study. The measured ODC of the PLA-PEG HbP was very close to that of the native hemoglobin, and the corresponding P(50) (26.1 mmHg) was also near to the native precursor protein (27.3 mmHg), indicative of the validity of the method proposed. To further verify the method proposed, the oxygen binding-releasing capacity of the HbPs prepared by PCL, PCL-PEG, PLA were also investigated with human blood as control. These results indicated that the method developed here enabled accurate and noninvasive determination of the oxygen binding-releasing capacity of the biodegradable polymeric oxygen carriers.

In vitro macrophage uptake and in vivo biodistribution of PLA-PEG nanoparticles loaded with hemoglobin as blood substitutes: effect of PEG content.

The aim of the present work is to investigate the effect of PEG content in copolymer on physicochemical properties, in vitro macrophage uptake, in vivo pharmacokinetics and biodistribution of poly(lactic acid) (PLA)-poly(ethylene glycol) (PEG) hemoglobin (Hb)-loaded nanoparticles (HbP) used as blood substitutes. The HbP were prepared from PLA and PLA-PEG copolymer of varying PEG contents (5, 10, and 20 wt%) by a modified w/o/w method and characterized with regard to their morphology, size, surface charge, drug loading, surface hydrophilicity, and PEG coating efficiency. The in vitro macrophage uptake, in vivo pharmacokinetics, and biodistribution following intravenous administration in mice of HbP labeled with 6-coumarin, were evaluated. The HbP prepared were all in the range of 100-200 nm with highest encapsulation efficiency 87.89%, surface charge -10 to -33 mV, static contact angle from 54.25 degrees to 68.27 degrees , and PEG coating efficiency higher than 80%. Compared with PLA HbP, PEGylation could notably avoid the macrophage uptake of HbP, in particular when the PEG content was 10 wt%, a minimum uptake (6.76%) was achieved after 1 h cultivation. In vivo, besides plasma, the major cumulative organ was the liver. All PLA-PEG HbP exhibited dramatically prolonged blood circulation and reduced liver accumulation, compared with the corresponding PLA HbP. The PEG content in copolymer affected significantly the survival time in blood. Optimum PEG coating (10 wt%) appeared to exist leading to the most prolonged blood circulation of PLA-PEG HbP, with a half-life of 34.3 h, much longer than that obtained by others (24.2 h). These results demonstrated that PEG 10 wt% modified PLA HbP with suitable size, surface charge, and surface hydrophilicity, has a promising potential as long-circulating oxygen carriers with desirable biocompatibility and biofunctionality.

[Effects of surfactant and solvent on the encapsulation efficiency and size in using double emulsion method for preparing bovine hemoglobin loaded nanoparticles as blood substitutes].

On the basis of previous researches, we have prepared Bovine hemoglobin-loaded nanoparticles (HbP), using the double emulsion method. More mild dispersing treatment was employed during the primary and secondary emulsion; over 97% encapsulation efficiency (EE%) and an average size about 286 nm were achieved by using surfactants, screening solvents, as well as avoiding the traditional strong dispersing process. The value of Hydrophile-lipophile balance in oil phase exerted a significant effect on EE% and led to higher EE% when matched with the surfactants in outer aqueous phase. When compared with the sole solvent Span80, the mixed surfactants such as Poloxemer188/Span80 stabilized the emulsion more efficiently and increased the EE%. The higher concentration of surfactants resulted in higher EE% and narrower size distribution. But over some amount, the surfactants had no significant effect on EE%, resulting in larger size and polydispersity index (PDI). The appropriate removal rate of solvents contributes to higher EE%, smaller size and PDI.

[Progress of researches on drug-loaded nanoparticles].

The progress of researches on drug-loaded nanoparticles was summarized in this review. The major emphasis was laid on the selection of wall polymers, technology of preparation, surface modification, investigation of release in vitro and biocompatibility evaluation. Additionally, we envisioned a perspective regarding the development in this field. With the development of synthesis of biodegradable polymer, with the appearance of novel equipment, and with the deep-going studies on modification of nanoparticles surface method, on fabrication of nanoparticles art as well as on evaluation of drug release and reaction between drug and organ, further researches in this field will open up the way to applications of drug-loaded nanoparticles in larger field.

[Preparation of hemoglobin-loaded nanoparticles and safety evaluation in vitro and in vivo].

Hemoglobin-loaded nano-sized particles with oxygen carrying capacity were prepared. All experiments were performed using biodegradable polymer poly (polyepsilon-caprolactone) (PCL) as matrix polymer. Optimized preparation parameters led to nanoparticles with well-defined characteristics such as size <200 nm, P50 27 mmHg and high encapsulation efficiency up to 99.4%. The results of in vitro and vivo studies suggested that Hb-loaded particles did not activate complements. After the nanoparticles suspension was injected into the mice via tail vein, the particles did not cause significant changes in total platelet counts. Apparently, the hemoglobin-loaded nanoparticles can serve as a potential candidate in substitution for red cells.

[Study on mass transfer behavior of hemoglobin-based nanocapsule surface].

Three dimensional structure of the surface is an important factor that influences the mass transfer behavior of hemoglobin-based nanocapsule surface. In this paper, the modified double emulsion method was used to fabricate the blood substitute of hemoglobin-based nanocapsules, and with the use of different molecular weight of PEG as probes, the effects of different technical conditions (such as primary emulsion, double emulsion, polymer, solvent, et al) in the processing on the three dimensional structure of the nanocapsule surface were investigated in details. Researches indicated that the water-soluable solvent, such as ethyl acetate and acetone could effectively modulate the pore size of the nanocapsule surface. With the increasing of the ratio of water-soluble solvent, the pore size of the nanocapsules firstly increased and then decreased. The increasing of the extra-water volume, the prolongation of the solvent evaporation time, and the improvement of the stirring speed resulted in a bigger pore size, but the increasing of the solvent volume and PEG polymer could reduce the pore size of nanocapsule surface.