Bibliometric insights into the inflammation and mitochondrial stress in ischemic stroke.

BACKGROUND: Research in the areas of inflammation and mitochondrial stress in ischemic stroke is rapidly expanding, but a comprehensive overview that integrates bibliometric trends with an in-depth review of molecular mechanisms is lacking. OBJECTIVE: To map the evolving landscape of research using bibliometric analysis and to detail the molecular mechanisms that underpin these trends, emphasizing their implications in ischemic stroke. METHODS: We conducted a bibliometric analysis to identify key trends, top contributors, and focal research themes. In addition, we review recent research advances in mitochondrial stress and inflammation in ischemic stroke to gain a detailed understanding of the pathophysiological processes involved. CONCLUSION: Our integrative approach not only highlights the growing research interest and collaborations but also provides a detailed exploration of the molecular mechanisms that are central to the pathology of ischemic stroke. This synthesis offers valuable insights for researchers and paves the way for targeted therapeutic interventions.

A bioactive nanocomposite integrated specific TAMs target and synergistic TAMs repolarization for effective cancer immunotherapy.

Reactive oxygen species (ROS) generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages (TAMs) toward the anti-tumor M1 phenotype, representing a promising cancer immunotherapy strategy. Nevertheless, their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers. Here, a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy. Colloidal mesoporous silica nanoparticles (CMSN) are fabricated to encapsulate photosensitizer-Indocyanine Green (ICG) to improve their stability. Then ginseng-derived exosome (GsE) was coated on the surface of ICG/CMSN for targeting TAMs, as well as repolarizing TAMs concurrently, named ICG/CMSN@GsE. As expected, with the synergism of ICG and GsE, ICG/CMSN@GsE exhibited better stability, mild generation of ROS, favorable specificity toward M2-like macrophages, enhancing drug retention in tumors and superior TAMs repolarization potency, then exerted a potent antitumor effect. In vivo, experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage. Taken together, by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform, ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.

Genetically predicted type 2 diabetes mellitus mediates the causal association between plasma uric acid and ischemic stroke.

OBJECTIVE: This study conducts a systematic investigation into the causal relationships between plasma uric acid levels and subtypes of ischemic stroke (IS), as well as the extent to which Type 2 diabetes mellitus (T2DM) mediates this relationship. BACKGROUND: There is a known association between Uric acid and IS but whether they have a causal relationship remains unclear. This study aims to determine whether a genetic predisposition to uric acid is causally linked to IS, including three subtypes, and to determine the mediating role of T2DM. METHODS: Bidirectional Mendelian randomization (MR) analyses was initially used to explore the causal relationship between uric acid and three subtypes of IS. Two-step MR methods were then used to investigate the role of T2DM in mediating the effect of uric acid and IS with its subtypes. RESULTS: A primary analysis showed uric acid had a markedly causal association with IS (IVW, OR 1.23; 95 % CI, 1.13 - 1.34; p = 6.39 × 10-9), and two subtypes of IS, Large-vessel atherosclerotic stroke LAS (IVW, OR 1.25; 95 % CI, 1.03 - 1.53; p = 0.026) and small vessel stroke (SVS) (IVW, OR 1.20; 95 % CI, 1.00 - 1.43; p = 0.049), but not with cardioembolic stroke (CES)(IVW, OR 1.00; 95 % CI, 0.87 - 1.15; p = 0.993). Two-step MR results showed that T2DM mediated the association between uric acid and LAS and SVS, accounting for 13.85 % (p = 0.025) and 13.57 % (p = 0.028), respectively. CONCLUSIONS: The study suggests that genetic predisposition to uric acid is linked to a greater risk of IS, especially LAS and SVS. T2DM might mediate a significant proportion of the associations between uric acid and LAS as well as SVS.

Size effect of mesoporous silica nanoparticles on regulating the immune effect of oral influenza split vaccine.

Mucosal immunization is a powerful weapon against viral infection. In this paper, large pore mesoporous silica nanoparticles (LMSN) with different particle sizes were synthesized for loading influenza split vaccine (SV) to explore the effect of nanoparticle sizes on mucosal immunization and adjuvant efficacy. Interestingly, it was found that among the three particle sizes of nanoparticles, only LMSN-M with around 250 nm could significantly enhance the mucosal immune effect of SV, possessing adjuvant effect. The results indicated that particle size affected the adjuvant effect of LMSN. There was no apparent difference in vaccine loading capacity of LMSN with different particle sizes, but the release of SV depended on the pore length of LMSN. The adjuvant effect of LMSN-M was attributed to its higher cellular uptake performance, intestine absorption and transport efficiency, and the ability to stimulate the maturation of dendritic cells. Simultaneously, compared with LMSN-S and LMSN-L, the more retention of LMSN-M in mesenteric lymph nodes increased the chance of interaction between vaccine and immune system, resulting in the enhanced immunity. This is the first time to study the impact of particle size of LMSN adjuvant on improving mucosal immunity of oral influenza vaccine, and the present work provides a scientific reference for adjuvant design of oral vaccine.

Glucose-responsive insulin microneedle patches for long-acting delivery and release visualization.

Limited drug loading and incomplete drug release are two major obstacles that traditional polymeric microneedles (MNs) have to overcome. For smart controlled-release MNs, since drug release duration is uncertain, a clear indication of the finish of drug release is also important for patient guidance on the timing of the next dose. In this study, MN with a triple structure of a glucose-responsive shell, loaded insulin powders and a colored propelling inner core (inspired by the mechanism of osmotic pump) was innovatively constructed. The MN patch could release insulin according to blood glucose levels (BGLs) and had excellent drug loading, more complete drug release, and good drug stability, which significantly prolonged the normoglycemic time. An approximately 0.3 cm2 patch has a hypoglycemic effect on diabetic mice for up to 24 h. Moreover, the fading of the inner core could indicate the release process of the loaded drug and can help to facilitate uninterrupted closed loop therapy for patients. The designed triple MN structure is also suitable, and can be used in the design of other smart MN drug delivery systems to further improve their drug loading capacity and simultaneously achieve more complete, smart controlled and visualized drug release.

A universal powder-laden crosslinked chitosan microneedle patch for high-dose controllable drug delivery.

In this study, we constructed a novel powder-laden core-shell crosslinked chitosan microneedle patch for high-dose and controllable delivery of various drugs, including both macromolecular biological drugs and small-molecule chemical drugs. Direct loading of drug powders greatly improved drug loading capacity and minimized degradation. The results of the in vitro drug release study suggested that the release behaviors of the most tested drugs (both macromolecular drugs and small-molecule drugs) can be tuned by adjusting the crosslink density of the microneedle shell to achieve either rapid or sustained release of the loaded drug. The in vivo hypoglycemic efficacy test in streptozotocin-induced diabetic mice further proved that the onset and duration of the insulin-laden patch can be customized by adjusting the crosslink density. Furthermore, a combination of microneedle patches with different crosslink densities not only rapidly reduced blood glucose levels to normoglycemic levels (within 1 h) but also maintained normoglycemia for up to 36 h. The insulin loaded in the patch also showed good stability during storage at 40 °C for 6 months. Our results suggest that this powder-laden patch represents a strong candidate for addressing the multiple challenges in the preparation and application of polymeric microneedles and shows promise in clinical applications.

Optimized strategies of ROS-based nanodynamic therapies for tumor theranostics.

Reactive oxygen species (ROS) play a crucial role in regulating the metabolism of tumor growth, metastasis, death and other biological processes. ROS-based nanodynamic therapies (NDTs) are becoming attractive due to non-invasive, low side effects and tumor-specific advantages. NDTs have rapidly developed into numerous branches, such as photodynamic therapy, chemodynamic therapy, sonodynamic therapy and so on. However, the complexity of the tumor microenvironment and the limitations of existing sensitizers have greatly restricted the therapeutic effects of NDTs, which heavily rely on ROS levels. To address the limitations of NDTs, various strategies have been developed to increase ROS yield, which is an urgent aspect for the positive development of NDTs. In this review, the nanodynamic potentiation strategies in terms of unique properties and universalities of NDTs are comprehensively outlined. We mainly summarize the current dilemmas faced by each NDT and the respective solutions. Meanwhile, the NDTs universalities-based potentiation strategies and NDTs-based combined treatments are elaborated. Finally, we conclude with a discussion of the key issues and challenges faced in the development and clinical transformation of NDTs.

Bibliometric and visualization analysis of matrix metalloproteinases in ischemic stroke from 1992 to 2022.

Background: Matrix metalloproteinases (MMPs) are important players in the complex pathophysiology of ischemic stroke (IS). Recent studies have shown that tremendous progress has been made in the research of MMPs in IS. However, a comprehensive bibliometric analysis is lacking in this research field. This study aimed to introduce the research status as well as hotspots and explore the field of MMPs in IS from a bibliometric perspective. Methods: This study collected 1,441 records related to MMPs in IS from 1979 to 2022 in the web of science core collection (WoSCC) database, among them the first paper was published in 1992. CiteSpace, VOSviewer, and R package "bibliometrix" software were used to analyze the publication type, author, institution, country, keywords, and other relevant data in detail, and made descriptive statistics to provide new ideas for future clinical and scientific research. Results: The change in the number of publications related to MMPs in IS can be divided into three stages: the first stage was from 1992 to 2012, when the number of publications increased steadily; the second stage was from 2013 to 2017, when the number of publications was relatively stable; the third stage was from 2018 to 2022, when the number of publications began to decline. The United States and China, contributing more than 64% of publications, were the main drivers for research in this field. Universities in the United States were the most active institutions and contributed the most publications. STROKE is the most popular journal in this field with the largest publications as well as the most co-cited journal. Rosenberg GA was the most prolific writer and has the most citations. "Clinical," "Medical," "Neurology," "Immunology" and "Biochemistry molecular biology" were the main research areas of MMPs in IS. "Molecular regulation," "Metalloproteinase-9 concentration," "Clinical translation" and "Cerebral ischemia-reperfusion" are the primary keywords clusters in this field. Conclusion: This is the first bibliometric study that comprehensively mapped out the knowledge structure and development trends in the research field of MMPs in IS in recent 30 years, which will provide a reference for scholars studying this field.

Neuroinflammatory Biomarkers in the Brain, Cerebrospinal Fluid, and Blood After Ischemic Stroke.

The most frequent type of stroke, known as ischemic stroke (IS), is a significant global public health issue. The pathological process of IS and post-IS episodes has not yet been fully explored, but neuroinflammation has been identified as one of the key processes. Biomarkers are objective indicators used to assess normal or pathological processes, evaluate responses to treatment, and predict outcomes, and some biomarkers can also be used as therapeutic targets. After IS, various molecules are produced by different cell types, such as microglia, astrocytes, infiltrating leukocytes, endothelial cells, and damaged neurons, that participate in the neuroinflammatory response within the ischemic brain region. These molecules may either promote or inhibit neuroinflammation and may be released into extracellular spaces, including cerebrospinal fluid (CSF) and blood, due to reasons such as BBB damage. These neuroinflammatory molecules should be valued as biomarkers to monitor whether their expression levels in the blood, CSF, and brain correlate with the diagnosis and prognosis of IS patients or whether they have potential as therapeutic targets. In addition, although some molecules do not directly participate in the process of neuroinflammation, they have been reported to have potential diagnostic or therapeutic value against post-IS neuroinflammation, and these molecules will also be listed. In this review, we summarize the neuroinflammatory biomarkers in the brain, CSF, and blood after an IS episode and the potential value of these biomarkers for the diagnosis, treatment, and prognosis of IS patients.

Degradable iron-rich mesoporous dopamine as a dual-glutathione depletion nanoplatform for photothermal-enhanced ferroptosis and chemodynamic therapy.

Glutathione (GSH) is a crucial factor in limiting the effects of chemodynamic therapy (CDT) and ferroptosis, an iron-based cell death pathway. Based on this, we constructed iron-rich mesoporous dopamine (MPDA@Fe) nanovehicles with a dual-GSH depletion function by combining MPDA and Fe. Poly (ethylene glycol) (PEG) was further modified to provide desirable stability (PM@Fe) and glucose oxidase (GOx) was grafted onto PM@Fe (GPM@Fe) to address the limitation of hydrogen peroxide (H2O2). After the nanoparticles reached the tumor site, the weakly acidic microenvironment promoted the release of Fe. Then FeII reacted with H2O2 to generate hydroxyl radical (OH) and FeIII. The generated FeIII was reduced to FeII by GSH, which circularly participated in the Fenton reaction and continuously produced tumor inhibitory free radicals. Meanwhile, GOx consumed glucose to provide H2O2 for the reaction. MPDA had also been reported to deplete GSH. Therefore, dual consumption of GSH led to the destruction of intracellular redox balance and inhibition of glutathione-dependent peroxidase 4 (GPX4) expression, resulting in an increase in lipid peroxides (LPO) and further induction of ferroptosis. Additionally, MPDA-mediated photothermal therapy (PTT) raised the temperature of tumor area and produced photothermal-enhanced cascade effects. Hence, the synergistic strategy that combined dual-GSH depletion-induced ferroptosis, enhanced CDT and photothermal cascade enhancement based on MPDA@Fe could provide more directions for designing nanomedicines for cancer treatment.

Biomimetic smart mesoporous carbon nanozyme as a dual-GSH depletion agent and O2 generator for enhanced photodynamic therapy.

Photodynamic therapy (PDT) has been thriving in the theranostics of cancer in recent years. However, due to a series of problems such as high concentration of GSH and insufficient O2 partial pressure in the tumor micro-environment, it is difficult to achieve the desired therapeutic effects with single PDT. Mesoporous carbon (MC-COOH) has been widely used in photothermal therapy (PTT) due to its high photothermal conversion efficiency and drug loading. In addition, we have discovered that MC-COOH owned high-efficiency glutathione oxidase-like activity for intracellular lasting GSH consumption. Hence, a smart mesoporous carbon nanozyme (CCM) was designed as a dual-GSH depletion agent and O2 generator combined with PTT to overcome the dilemma of PDT. MnO2-doped carbon nanozyme (MC-Mn) was developed as the photothermal vehicles for the efficient loading of photosensitizer (Ce6). Subsequently, 4T1 membrane-coated nanozyme (Ce6/CCM) was constructed to achieve homologous targeting capability. The carbon nanozyme owned the sustained dual-GSH depletion function through MC-COOH and MnO2, which greatly destroyed the antioxidant system of the tumor. Meanwhile, MnO2 could produce affluent O2 in the presence of H2O2, thereby alleviating the hypoxic state of tumor tissues and further promoting the generation of ROS. In addition, the novel carbon nanozyme was designed as photoacoustic imaging (PAI) agent and magnetic resonance imaging (MRI) contrast for real-time imaging during tumor therapy. In summary, this work showed that the biomimetic carbon nanozyme could be used as dual-GSH depletion agent and O2 generator for dual-mode imaging-guided PTT-PDT. STATEMENT OF SIGNIFICANCE: - MC-COOH with highly efficient GSH-OXD activity was first discovered and applied in PDT. - MnO2 acted as an O2 generator and GSH depletion agent to enhance PDT. - The tumor-targeting ability of the nanozyme was improved by cell membrane camouflage. - CCM nanozyme possesses both PAI and MRI dual-mode imaging modalities to guide PDT/PTT.

Approaches and materials for endocytosis-independent intracellular delivery of proteins.

The intracellular delivery of proteins is of great significance. For diseases such as cancer, heart disease and neurodegenerative diseases, many important pharmacological targets are located inside cells. For genetic engineering and cell engineering, various functional proteins need to be delivered into cells for gene editing or cell state regulation. However, most existing protein delivery strategies involve endosomal escape (endocytosis-dependent), resulting in inefficient delivery due to endosome trapping. In contrast, endocytosis-independent intracellular delivery, which refers to the directly delivery of proteins across the cell membrane to the cytoplasm, will bypass the low efficiency of early endosomal escape, avoid protein inactivation caused by late endosome/lysosome, fundamentally improve the intracellular delivery efficiency, and open up a new way for intracellular protein delivery. In this review, the latest advances in direct intracellular delivery of proteins through membrane perforation, membrane translocation, and membrane fusion were summarized. The mechanisms, related materials and potential therapeutic in living cells/in vivo for each approach were discussed in detail, and the future development in this promising field was briefly presented.

A biomimetic nanocomposite made of a ginger-derived exosome and an inorganic framework for high-performance delivery of oral antibodies.

For inflammatory bowel disease (IBD) therapy, systemic exposure of anti-TNF-α antibodies brought by current clinical injection always causes serious adverse effects. Colon-targeted delivery of anti-TNF-α antibodies through the oral route is of great importance but remains a formidable challenge. Here, we reported a biomimetic nanocomposite made of a ginger-derived exosome and an inorganic framework for this purpose. A large mesoporous silicon nanoparticle (LMSN) was uniquely customized for the antibody (infliximab, INF) to load it at high levels up to 61.3 wt% and prevent its aggregation. Exosome-like nanovesicles were isolated from ginger (GE) with a high-level production (17.5 mg kg-1). Then, ultrasound was used to coat GE onto the LMSN to obtain the biomimetic nanocomposite LMSN@GE. As expected, LMSN@GE showed advantages in the oral delivery of INF: stability in the gastrointestinal tract, colon-targeted delivery and high intestinal epithelium permeability. Amazingly, GE also presented an anti-inflammatory effect by blocking the NLRP3 inflammasome in addition to its delivery value. As a result, INF/LMSN@GE showed a significantly higher efficacy in colitis mice compared to the intravenously administered INF. This work provides new insights into colon-targeted delivery of anti-TNF-α antibodies via the oral route. Moreover, it puts forward a novel strategy for drug delivery using one therapeutic agent (herb-derived exosomes).

A versatile gas-generator promoting drug release and oxygen replenishment for amplifying photodynamic-chemotherapy synergetic anti-tumor effects.

Excellent efficiency of combinational therapy of chemotherapy and photodynamic therapy (PDT) highly depends on the amounts of drug and oxygen in tumor tissue. However, how to cleverly promote drug release accompanied with improving oxygen concentration remains a challenge. Herein, we proposed a gas-generator that realized a high drug loading and integrated facilitation of drug release with oxygen replenishment into a single and simple system, utilizing huge cavities and mesoporous channels of hollow mesoporous silica nanoparticles (HMSNs) for encapsulating oxygen (O2) saturated perfluoropentane (PFP) droplets, indocyanine green (ICG) and doxorubicin (DOX), biocompatible polydopamine (PDA) as the gatekeepers. Under irradiation of 808 nm laser, the thermal effect of PDA caused PFP droplets occur liquid-gas phase transition that triggered the burst release of DOX and O2, finally amplifying the synergetic effects of PDT and chemotherapy both in vitro and in vivo. The influence of PFP, GSH and laser on drug release kinetic was explored through mathematical models. Notably, the mechanism of gas-generator on accelerating drug release under irradiation based on doing volume work and enhancing diffusion coefficient was clarified by researching the relation between DOX release, PFP release and temperature change. Additionally, the way of replenishing O2 did not rely on intracellular components but timely offered abundant "fuels" for producing reactive oxygen species (ROS) when compared with traditional manners. This work provides a new research strategy for boosting drug release and opens an avenue for constructing multifunctional controlled delivery systems.

Zwitterion-functionalized mesoporous silica nanoparticles for enhancing oral delivery of protein drugs by overcoming multiple gastrointestinal barriers.

Oral delivery of protein or peptide drugs confronts several barriers, the intestinal epithelium and the mucus barrier on the gastrointestinal tract is deemed to be the toughest obstacles. However, overcoming these two obstacles requires contradictory surface properties of a nanocarrier. In the present work, mesoporous silica nanoparticles (MSNs) were modified with deoxycholic acid (DC) and coated with sulfobetaine 12 (SB12) for the first time to achieve both improved mucus permeation and transepithelial absorption. MSNs modified with stearic acid and coated with dilauroylphosphatidylcholine (DLPC) or Pluronic P123 were also prepared as controls. The SB12 coated DC modified MSN had high drug loading of 22.2%. The zwitterion coating endows the MSN improved mucus penetrating ability. In addition, the carrier also showed remarkable affinity with epithelial cells. The cellular uptake was significantly improved (10-fold for Caco-2 cells and 8-fold for E12 cells). The results also indicated that the DC modified carrier was able to avoid entry into lysosomes. It can increase the absorption of loaded insulin in all intestine segments and showed outstanding hypoglycemic effect in diabetic rats. The results suggest the zwitterion-functionalized MSNs might be a good candidate for oral protein delivery.

Multi-stimuli responsive mesoporous silica-coated carbon nanoparticles for chemo-photothermal therapy of tumor.

In this work, a traceable dual-porous mesoporous silica-coated mesoporous carbon nanocomposite (MCN@Si) with high drug loading capacity and high photothermal conversion efficiency (30.5 %) was successfully prepared. Based on the nanocomposite, a pH/redox/near infrared (NIR) multi-stimuli responsive drug delivery system was constructed to realize the accurate drug delivery, drug controlled release and chemo-photothermal synergistic antitumor therapy. MCN@Si was used as a vehicle to load doxorubicin (DOX) with a high drug loading efficacy of 48.2 % and a NIR absorbance agent for photothermal therapy and NIR thermal imaging. Carbon dots (CDs) with proper size were covalently attached to the surface of MCN@Si via disulfide bonds to block the mesopores, preventing DOX premature release from DOX/MCN@Si-CDs. Besides, CDs were served as fluorescent probe to prove the visualization potential of the drug delivery system. DOX was rapidly released at the condition of low pH and high GSH concentration due to the breakage of disulfide bonds and protonation of DOX. Moreover, the local hyperthermia generated by MCN@Si-CDs under NIR irradiation could not only directly kill cells, but also accelerate DOX release and enhance cells sensitivity and permeability. Two-dimensional cells and three-dimensional tumor spheroids assays illustrated that DOX/MCN@Si-CDs + NIR group exhibited a superior thermochemotherapy synergistic treatment effect and the combination index (CI) was 0.378. Biodistribution study showed the biosecurity of preparations and its prolonged detention time in tumor sites. Besides, antitumor experiment in vivo also performed the excellent synergistic inhibition effect. All the results demonstrated that DOX/MCN@Si-CDs is a traceable multi-stimuli responsive nanodelivery system and can achieve efficient chemo-photothermal synergistic antitumor therapy.

Protective properties of mesocellular silica foams against aggregation and enzymatic hydrolysis of loaded proteins for oral protein delivery.

Numerous types of mesoporous silica nanoparticles (MSNs) have been studied as carriers for small molecular drugs. However, few reports have been conducted on small MSNs having large pores, and that are suitable for loading and orally delivering therapeutic proteins. In particular, their protective properties against aggregation and enzymatic hydrolysis of loaded proteins have been rarely studied. In this study, mesocellular silica foams (MCFs) with large and different pore sizes were prepared. The loading and release behaviors of three model proteins with different molecular weights were studied. The protective properties of the MCFs against enzymatic hydrolysis of the loaded proteins were tested by sodium dodecyl sulfate polyacrylamide gel electrophoresis and high-performance liquid chromatography. The protecting effects of the MCFs against conformational change and aggregation of the loaded proteins were evaluated by circular dichroism and synchronous fluorescence spectra. Diabetic mice were inducted to evaluate in a preliminary manner the in vivo hypoglycemic effect of insulin loaded MCFs. The prepared MCFs showed rapid and high drug loading (up to 43%) of proteins. The release of proteins was tunable depending on the pore size. The lysozyme loaded MCFs could release 87% intact protein after incubation with pancreatin for 0.5 h. The digestion times for the insulin loaded in MCFs were prolonged to twice that of naked insulin. The secondary conformational changes for the insulin loaded in MCFs were only 1/40 to 1/20 of that of naked insulin incubated with Zn2+. Orally administered insulin-loaded MCF could reduce the blood glucose level to 69%. The prepared MCFs could effectively protect the loaded proteins from aggregation and enzymatic hydrolysis, thus exhibiting potential for application as carriers for protein delivery.

Polydopamine-coated mesoporous silica nanoparticles for multi-responsive drug delivery and combined chemo-photothermal therapy.

Synergistic therapy of chemotherapy and photothermal therapy exhibits great potential to improve the therapeutic efficiency for cancer therapy. In this study, a new biocompatible multiple sensitive drug delivery system (DDS) was synthesized by covering a polydopamine (PDA) layer on doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) via disulfide bonds (MSN-SS-PDA/DOX). PDA worked as a photothermal therapy (PTT) agent and also a gate keeper to control drug release, which was highly sensitive to pH and could prolong the residence time, simultaneously increase water solubility and biocompatibility of the nanoparticles. The DDS exhibited excellent monodispersity, redox/pH/NIR-multi-dependent release characteristics, remarkable photothermal conversion property (photothermal conversion efficiency η = 40.21%) and outstanding tumor cell synergistic killing efficiency of chemotherapy and photothermal therapy (combination index CI = 0.175). The biodistribution and pharmacodynamics experiments of MSN-SS-PDA/DOX in 4T1 tumor models indicated that MSN-SS-PDA made more DOX accumulate in tumor tissue than free DOX, extend circulation time of DOX in the body, and exhibit a significant synergistic antitumor efficacy. Meanwhile, the tumor growth was remarkably inhibited, which was much more obvious than any monotherapy effect. Thus, the novel nanoplatform presents a promising future as a drug delivery system for combination therapy.

A comparison between sphere and rod nanoparticles regarding their in vivo biological behavior and pharmacokinetics.

In recent years, spherical nanoparticles has been studied extensively on biomedical applications including bioimaging and biosensing, diagnostics and theranostics, but the effect of the shape of nanoparticles has received little attention. In the present study, we designed three different shaped fluorescent mesoporous silica nanoparticles (MSNs), long rod nanoparticles (NLR), short rod nanoparticles (NSR), and spherical nanoparticles (NS) to systematically examine their behavior in vivo after oral administration. The results of the ex vivo optical imaging study in mice indicated that rod nanoparticles had a longer residence time in the gastrointestinal compared with spherical nanoparticles. The in vivo biodistribution showed that all the orally administered MSNs were mainly taken up by the liver, and kidney. NLR had a great capacity to overcoming rapid clearance by the RES and exhibited a longer circulation in the blood than NSR and NS. During renal excretion, the spherical nanoparticles were cleared faster than rod nanoparticles. In addition, it was also found that MSNs can be degraded in vivo and NSR were degraded faster than NLR and NS probably owing to their higher specific surface area. The pharmacokinetic results demonstrated that nifedipine(NI)-loaded NLR had a higher bioavailability than NI-loaded NSR and NS.

A Eu(3+)/Gd(3+)-EDTA-doped structurally controllable hollow mesoporous carbon for improving the oral bioavailability of insoluble drugs and in vivo tracing.

A structurally controllable fluorescence-labeled hollow mesoporous carbon (HMC) was simply prepared to improve the oral bioavailability of insoluble drugs and further trace their delivery process in vivo. The hollow structure was derived from an inverse replica process using mesoporous silica as a template and the fluorescent label was prepared by doping the carboxylated HMC with a confinement of Eu(3+)/Gd(3+)-EDTA. The physicochemical properties of the composites were systematically characterized by transmission electron microscopy, Fourier transform infrared spectroscopy and photoluminescence spectra tests prior to studying their effects on drug-release behavior and biodistribution. As a result, the thickness of the carrier's shell was adjusted from 70 nm to 130 nm and the maximum drug loading was up to 73.6%. The model drug carvedilol (CAR) showed sustained release behavior compared to CAR commercial capsules, and the dissolution rate slowed down as the shells got thicker. AUC0-48h and Tmax were enlarged 2.2 and 6.5 fold, respectively, which demonstrated that oral bioavailability was successfully improved. Bioimaging tests showed that the novel carbon vehicle had a long residence time in the gastrointestinal tract. In short, the newly designed HMC is a promising drug carrier for both oral bioavailability improvement and in vivo tracing.