Targeting Of Nanoparticles Research Articles

Bile Acid Nanoparticles - An Emerging Approach for Site Specific Drug Targeting

Abstract: Bile acids, a group of steroidal acids present in the bile act as biological surfactants and ligands for bile acid transporter proteins for signalling molecules to perform various paracrine and endocrine functions. The enterohepatic circulation of bile acids can be exploited to develop at-tractive drug delivery approaches with improved targetability of facial amphiphiles and enhanced drug bioavailability by improving absorption and metabolic stability. The effectiveness, safety and targetability of nanoparticles conjugated with bile acids and salts have been discussed in the present review. Various modifications of bile acids promoting absorption and oral bioavailability of drugs for treatment of various disease conditions such as cancer, diabetes and psychosis has al-so been discussed. Additionally, neuroprotective effect of bile acids and salts has demonstrated utility in various neurodegenerative disorders. Nanoparticles based on bile acids and salts repre-sent an area of emergent interest due to their unique and modifiable properties for improving ef-fectiveness of drugs.

Targeted Analysis of Mitochondrial Protein Conformations and Interactions by Endogenous ROS-Triggered Cross-Linker Release.

The study of in situ conformations and interactions of mitochondrial proteins plays a crucial role in understanding their biological functions. Current chemical cross-linking mass spectrometry (CX-MS) has difficulty in achieving in-depth analysis of mitochondrial proteins for cells without genetic modification. Herein, this work develops the reactive oxygen species (ROS)-responsive cross-linker delivery nanoparticles (R-CDNP) targeting mitochondria. R-CDNP contains mitochondria-targeting module triphenylphosphine, ROS-responsive module thioketal, loading module poly(lactic-co-glycolic acid) (PLGA), and polyethylene glycol (PEG), and cross-linker module disuccinimidyl suberate (DSS). After targeting mitochondria, ROS-triggered cross-linker release improves the cross-linking coverage of mitochondria in situ. In total, this work identifies 2103 cross-linked sites of 572 mitochondrial proteins in HepG2 cells. 1718 intra-links reveal dynamic conformations involving chaperones with ATP-dependent conformation cycles, and 385 inter-links reveal dynamic interactions involving OXPHOS complexes and 27 pairs of possible potential interactions. These results signify that R-CDNP can achieve dynamic conformation and interaction analysis of mitochondrial proteins in living cells, thereby contributing to a better understanding of their biological functions.

Functionalized Nanomaterials In Pancreatic Cancer Theranostics And Molecular Imaging.

Pancreatic cancer (PC) is one of the most fatal malignancies in the world. This lethality persists due to lack of effective and efficient treatment strategies. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive epithelial malignancy which has a high incidence rate and contributes to overall cancer fatalities. As of 2022, pancreatic cancer contributes to about 3 % of all cancers globally. Over the years, research has characterised germline predisposition, the origin cell, precursor lesions, genetic alterations, structural alterations, transcriptional changes, tumour heterogeneity, metastatic progression, and the tumour microenvironment, which has improved the understanding of PDAC carcinogenesis. By using molecular-based target therapies, these fundamental advancements support primary prevention, screening, early detection, and treatment. The focus of this review is the use of targeted nanoparticles as an alternative to conventional pancreatic cancer treatment due to the various side effects of the latter. The principles of nanoparticle based cancer therapy is efficient targeting of tumour cells via enhanced permeability and retention (EPR) effects and decrease the chemotherapy side effects due to their non-specificity. To increase the efficiency of existing therapies and modify target nanoparticles, several molecular markers of pancreatic cancer cells have been identified. Thus pancreatic cancer cells can be detected using appropriately functionalized nanoparticles with specific signalling molecules. Once cancer has been identified, these nanoparticles can kill the tumour by inducing hyperthermia, medication delivery, immunotherapy or gene therapy. As potent co-delivery methods for adjuvants and tumor-associated antigens; nanoparticles (NPs) have demonstrated significant promise as delivery vehicles in cancer therapy. This ensures the precise internalization of the functionalized nanoparticle and thus also activates the immune system effectively against tumor cells. This review also discusses the immunological factors behind the uptake of functionalized nanoparticles in cancer therapies. Theranostics, which combine imaging and therapeutic chemicals in a single nanocarrier, are the next generation of medicines. Pancreatic cancer treatment may be revolutionised by the development of a tailored nanocarrier with diagnostic, therapeutic, and imaging capabilities. It is extremely difficult to incorporate various therapeutic modalities into a single nanocarrier without compromising the individual functionalities. Surface modification of nanocarriers with antibodies or proteins will enable to attain multifunctionality which increases the efficiency of pancreatic cancer therapy.

Co-delivery of polyphyllin II and IR780 PLGA nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapy.

The clinical efficacy of immunotherapy for hepatocellular carcinoma (HCC) is significantly limited by the low immunogenicity of the tumor. Recent studies have revealed that both pyroptosis and photothermal therapy can effectively induce tumor immunogenic cell death (ICD) in liver cancer cells. Polyphyllin II (PPII), the major active component of Rhizoma Paridis, has been demonstrated for the first time to induce pyroptosis in tumor cells, while IR780 is activated by 808nm laser to transform light energy into heat energy, effectively eliminating tumor cells. However, both PPII and IR780 are afflicted with challenges such as low solubility and poor targeting, significantly limiting their utilization. To address these problems, the pyroptosis inducer PPII and photosensitizer IR780 were co-loaded in PLGA nanoparticles by precipitation method, and the aptamer AS1411 was modified on the surface of nanoparticles to construct the targeting nanoparticles (Apt/PPII/IR780-NPs). The nanoparticles exhibit a pH/NIR dual-response intelligent release feature, which realizes the targeted and controlled release of drugs in tumor site. Furthermore, it can rapidly release PPII to induce cell pyroptosis under laser irradiation, combining with IR780-based photothermal therapy exert a significant synergistic anti-tumor effect in vitro and in vivo. This process not only promotes maturation of DCs and activates effector T cells, thereby initiating adaptive immunity, but also generates enduring and effective immune memory. In addition, Apt/PPII/IR780-NPs significantly improved the Anti-PD-1 efficacy. In summary, chemo-photothermal therapy based on Apt/PPII/IR780-NPs can significantly enhance tumor ICD, which provides a promising new strategy for HCC immunotherapy.

Enhanced docetaxel therapeutic effect using dual targeted SRL-2 and TA1 aptamer conjugated micelles in inhibition Balb/c mice breast cancer model

Effective targeting and delivery of large amounts of medications into the cancer cells enhance their therapeutic efficacy through saturation of cellular defensive mechanisms, which is the most privilege of nano drug delivery systems (NDDS) compared to traditional approaches. Herein, we designed dual-pH/redox responsive DTX-loaded poly (β-amino ester) (PBAS) micelles decorated with a chimeric peptide and TA1 aptamer. In vitro and in vivo results demonstrated that the designed nanoplatform possessed an undetectable nature in the blood circulation, but after exposure to the tumor microenvironment (TME) of 4T1 breast cancer, it suddenly changed into dual targeting nanoparticles (NPs) (containing two ligands, SRL-2 and TA1 aptamer). The dual targeting NPs destruction in the high GSH and low pH conditions of the cancer cells led to amplified DTX release (around 70% at 24 h). The IC50 value of DTX-loaded MMP-9 sensitive heptapeptide/TA1 aptamer-modified poly (β-amino ester) (MST@PBAS) micelles and free DTX after 48 h of exposure was determined to be 1.5 µg/ml and 7.5 µg/ml, respectively. The nano-formulated DTX exhibited cytotoxicity that was 5-fold stronger than free DTX (Pvalue˂0.001). Cell cycle assay test results showed that following exposure to MST@PBAS micelles, a considerable rise in the sub G1 population (48%) suggested that apoptosis by cell cycle arrest had occurred. DTX-loaded MST@PBAS micelles revealed significantly higher (Pvalue ˂ 0.001) levels of early apoptosis (59.8%) than free DTX (44.7%). Interestingly, in vitro uptake studies showed a significantly higher TME accumulation of dual targeted NPs (6-fold) compared to single targeted NPs (Pvalue < 0.001) which further confirmed by in vivo biodistribution and fluorescent TUNEL assay experiments. NPs treated groups demonstrated notable tumor growth inhibition in 4T1 tumor bearing Balb/c mice by only 1/10th of the DTX therapeutic dose (TD) as a drug model. In conclusion, cleverly designed nanostructures here demonstrated improved anticancer effects by enhancing tumor targeting, delivering chemotherapeutic agents more accurately, promoting drug release, reducing the therapeutic dosage, and lowering side effects of anticancer drugs.

The Potential of Nanotechnology in Anti-Cancer Drug to Regulate Nrf2 Signaling for Cancer Therapeutic Purposes.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a regulator of the cellular antioxidant defense system that plays an important role in reducing the risk of various pathophysiological conditions, including cancer. Targeting Nrf2 presents an attractive therapeutic approach to overcome these challenges and improve cancer treatment outcomes. Nanoparticles, with their unique physicochemical properties, offer several advantages over conventional therapies for targeting Nrf2. These include enhanced stability, improved permeability and retention effect, and precise targeting capabilities. Moreover, delivery systems based on nanotechnology have shown promise in overcoming the limitations of conventional cancer therapies, including ineffective precision targeting and momentous complications. The therapeutic efficacy of Nrf2 inhibitors may be enhanced by using nanoparticles for specific drug targeting and deeper tissue penetration. This involves optimizing nanoparticle formulations, understanding their interactions with the biological environment, and ensuring their safety and biocompatibility. Effective nanoparticle formulations are being developed to transport Nrf2 inhibitors, which can significantly improve treatment outcomes and address the limitations of conventional cancer therapies. Further studies are needed to explore the potential of nanotechnology in targeting Nrf2 for cancer therapeutic purposes.

Hyaluronic acid/lactoferrin–coated polydatin/PLGA nanoparticles for active targeting of CD44 receptors in lung cancer

Traditional chemotherapeutic drugs lack optimal efficacy and invoke severe adverse effects in cancer patients. Polydatin (PD), a phytomedicine, has gradually gained attention due to its antitumor activity. However, its low solubility and poor bioavailability are still cornerstone issues. The present study aimed to fabricate and develop hyaluronic acid/lactoferrin–double coated PD/PLGA nanoparticles via a layer-by-layer self-assembly technique for active targeting of CD44 receptors in lung cancer. Different molecular weights (M.wt.) of HA (32 and 110 kDa) were exploited to study the relationship between the HA M.wt. and the NPs targeting efficacy. The optimized formulations were fully characterized. Their cytotoxicity and cellular uptake were investigated against A549 cell line by CCK-8 kit and fluorescence imaging, respectively. Finally, HA110/Lf-coated PD/PLGA NPs (F9) were subjected to a competitive inhibition study to prove internalization through CD44 overexpressed receptors. The results verified the fabrication of F9 with a particle size of 174.87 ± 3.97 nm and a zeta potential of −24.37 ± 1.19 mV as well as spherical NPs architecture. Importantly, it provoked enhanced cytotoxicity (IC50 = 0.57 ± 0.02 µg/mL) and superior cellular uptake efficacy. To conclude, the current investigation lays the foundation for the prospective therapeutic avenue of F9 for active targeting of CD44 receptors in lung cancer.

Patient-Specific Nanoparticle Targeting in Human Leukemia Blood.

Antibody-directed targeting of chemotherapeutic nanoparticles to primary human cancers holds promise for improving efficacy and reducing off-target toxicity. However, clinical responses to targeted nanomedicines are highly variable. Herein, we prepared and examined a matrix of 9 particles (organic and inorganic particles of three surface chemistries with and without antibody functionalization) and developed an ex vivo model to study the person-specific targeting of nanoparticles in whole blood of 15 patients with chronic lymphocytic leukemia (CLL). Generally, anti-CD20-functionalized poly(ethylene glycol) (PEG) nanoparticles efficiently targeted CLL cells, leading to low off-target phagocytosis by granulocytes and monocytes in the blood. However, there was up to 164-fold patient-to-patient variability in the CLL targeting. This was further exemplified through using clinically relevant PEGylated doxorubicin-encapsulated liposomes, which showed high interpersonal differences in CLL targeting (up to 234-fold differences) and off-target phagocytosis (up to 65- and 112-fold differences in granulocytes and monocytes, respectively). Off-target phagocytosis led to almost all monocytes being killed within 24 h of treatment. Variance of the off-target association of PEGylated liposomes with granulocytes and monocytes significantly correlated to anti-PEG immunoglobulin G levels in the blood of CLL patients. A negative correlation between CLL targeting of PEG particles and anti-PEG immunoglobulin M levels was found in the blood. Taken together, our study identifies anti-PEG antibodies as key proteins in modulating patient-specific targeting of PEGylated nanoparticles in human leukemia blood. Other factors, such as the antigen expression of targeted cells and fouling properties of nanoparticles, also play an important role in patient-specific targeting. The human leukemia blood assay we developed provides an ex vivo model to evaluate interpersonal variances in response to targeted nanomedicines.

Overcoming Hepatic Biotransformation Barrier of Gold Nanoparticles via Au-Se Bond for Enhanced In Vivo Active Targeting.

As a key metabolic function of the liver, the hepatic biotransformation process can alter the predesigned surface chemistry of nanoparticles in vivo, leading to hampered functionality and targeting ability. However, strategies to modulate the hepatic biotransformation of nanoparticles have been rarely explored. Herein, using indocyanine green (ICG)-conjugated gold nanoparticles that target liver hepatocytes as a model, we showed that merely changing the metal-ligand bond from gold-sulfur (Au-S) to gold-selenium (Au-Se) completely reshaped the hepatic biotransformation profiles of the nanoparticle as well as its targeting and transport behaviors in vivo. Compared with those of Au-S bond, Au-Se bond markedly slowed down nanoparticle biotransformation in liver sinusoids, enhanced ICG-mediated nanoparticle targeting to hepatocytes by 15-fold, and also altered nanoparticle intrahepatic transport, distribution, and clearance pathways. Moreover, we demonstrated that Au-Se bond could improve the active targeting of gold nanoparticles to hepatic tumors by reducing liver biotransformation-induced dissociation of targeting ligands. These discoveries not only deepen our understanding of nanoparticle biotransformation in the liver but also offer a strategy to overcome the biochemical barrier of hepatic biotransformation, providing guidance for the design and engineering of related nanomedicines by tuning their in vivo biotransformation profiles.

Mannose targeting of poly(lactic-co-glycolic acid): a promising approach for improving sublingual allergen-specific immunotherapy

Objective One of the most effective treatments for allergic respiratory diseases is allergen-specific sublingual immunotherapy (SLIT). While, mannose targeting has been applied in various immunostimulatory approaches, but it has not been investigated in sublingual allergen-specific immunosuppressive treatment. This study assesses mannose targeting for the ovalbumin (Ova) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles(NPs). Methods The emulsion-solvent evaporation method was employed for the synthesis of PLGA NPs containing Ova, and subsequently they attached to D-mannose. Ova-sensitized mice underwent treatment in different ways: subcutaneous administration of 10 µg Ova, sublingual administration of 5 and 10 µg Ova loaded in PLGA NPs, 5 and 10 µg Ova loaded in mannose-targeted PLGA NPs, 10 µg Ova, and 10 µg Ova loaded in dendritic cell-specific aptamer-attached PLGA NPs. Serum Ova-specific IgE and IgG2a levels, as well as IFN-γ, IL-4, IL-10, and IL-17a levels in the supernatant of Ova-stimulated splenocytes were measured. Splenocyte proliferation was assessed using an MTT assay, and also lung histological examinations, and nasal lavage fluid cell counting were performed. Results Ova-specific IgE, IL-4, IL-17a levels, eosinophil cell count, and splenocyte proliferation were remarkably reduced in the mice treated with mannose or aptamer targeted NPs compared to other groups. Also, IL-10 and IFN-γ levels were remarkably increased in the targeted NPs groups. Conclusion Our findings indicated that mannose targeting of PLGA NPs could decrease allergen dose and improve immunomodulatory effects of SLIT. However, this approach suggests an effective formulation for SLIT in the mice model, further studies with common allergens are needed for application in humans.

Rapid precision targeting of nanoparticles to lung via caveolae pumping system in endothelium.

Modern medicine seeks precision targeting, imaging and therapy to maximize efficacy and avoid toxicities. Nanoparticles (NPs) have tremendous yet unmet clinical potential to carry and deliver imaging and therapeutic agents systemically with tissue precision. But their size contributes to rapid scavenging by the reticuloendothelial system and poor penetration of key endothelial cell (EC) barriers, limiting target tissue uptake, safety and efficacy. Here we discover the ability of the EC caveolae pumping system to outpace scavenging and deliver NPs rapidly and specifically into the lungs. Gold and dendritic NPs are conjugated to antibodies targeting caveolae of the lung microvascular endothelium. SPECT-CT imaging and biodistribution analyses reveal that rat lungs extract most of the intravenous dose within minutes to achieve precision lung imaging and targeting with high lung concentrations exceeding peak blood levels. These results reveal how much ECs can both limit and promote tissue penetration of NPs and the power and size-dependent limitations of the caveolae pumping system. This study provides a new retargeting paradigm for NPs to avoid reticuloendothelial system uptake and achieve rapid precision nanodelivery for future diagnostic and therapeutic applications.

Targeted K-Edge Nanoprobes From Praseodymium and Hafnium for Ratiometric Tracking of Dual Biomarkers using Spectral Photon Counting CT.

Utilizing metal nanoprobes with unique K-edge identities to visualize complementary biological activities simultaneously can provide valuable information about complex biological processes. This study describes the design and preparation of an innovative pair of K-edge metal nanoprobes and demonstrates the feasibility of their simultaneous quantitative detection using spectral photon-counting computed tomography (SPCCT). Glycosaminoglycan (GAG) capped nanoparticles (ca. 15-20nm) targeting two distinct components of the cartilage tissue, namely, aggrecan (acan) and aggrecanase (acanase) are designed and synthesized. These targeted nanoparticles comprised of praseodymium (Pr) and hafnium (Hf), with well-separated K-edge energies, enable simultaneous and ratiometric imaging of dual biomarkers in cartilage tissue. Following extensive physico-chemical characterization of the ligand-targeted particles, the feasibility of homing dual biomarkers in vitro is demonstrated. The material discrimination and simultaneous quantification of these targeted particles are also achieved and corroborated with inductively coupled plasmon spectroscopy. For the first time, the use of praseodymium is reported as a contrast agent for SPCCT imaging and demonstrates the ability to pair it with hafnium nanoprobes for multicontrast imaging of diseases. Importantly, the potential for ratiometric molecular imaging and tracking of osteoarthritis (OA) progression is shown with SPCCT K-edge based imaging approach.

Protein absorption alters the cellular targeting of glycopolymeric nanoparticles

Glycopolymeric nanoparticles are widely employed in biomedical applications due to their high targeting ability, biocompatibility, and biodegradability. The pendant saccharides serve as targeting ligands to be explicitly coordinated to receptors on cell membrane surfaces. However, proteins in the blood often absorb onto the nanoparticle surface, potentially impacting the exposure and effectiveness of the saccharide ligands for targeted delivery. To elucidate the protein absorption effects, we prepared micelles decorated with different percentages of fructose moieties and evaluated the bioactivity of nanoparticles using 2D cell culture, tumor spheroid, liver organoid, and coculture models. The 2D cell culture model did not show a significant difference in activity between protein-coated and non-coated micelles. However, a dramatic decrease in cellular uptake and penetration ability of micelles was observed in 3D tumor spheroids after protein absorption. Additionally, protein absorption notably increased micelle uptake in liver organoids. In the coculture model, protein absorption reduced micelle uptake in tumor spheroids while favoring uptake in liver organoids. Our work suggests that decreasing non-specific protein absorption of glycopolymeric nanoparticles could enhance their delivery efficiency. These findings underscore the importance of understanding protein interactions in nanoparticle applications for drug delivery.

Towards a Switchable Nanoparticle Behavior Using Inverse Electron-Demand Diels-Alder Chemistry and Ectoenzyme-Based Ligand Activation

Nanoparticles (NPs) as drug delivery platforms encounter numerous obstacles on their journey from administration to the target site. Often, diametrically opposing particle properties are desirable to overcome biological and physical barriers. Therefore, stimuli-responsive NPs have been developed to allow for specific particle adaptation. In this work, it was demonstrated that NPs can be rendered switchable with respect to their interaction with a receptor through an external chemical stimulus. A combination of the inverse electron-demand Diels-Alder (iEDDA) reaction for subsequent NP functionalization and ectoenzyme-based ligand activation allowed for specific particle tailoring. Building on this, a two-step process for target cell recognition was developed: First, NPs were functionalized with Angiotensin-I (Ang-I) as inactive ligand using iEDDA chemistry. At the target site, the ligand was enzymatically processed to Angiotensin-ll (Ang-II) by cellular ectoenzymes. Ang-ll binds as active ligand to the angiotensin ll type 1 (AT1) receptor on the target cell surface. This enzymatic activation aims to minimize the biological effect of the ligand prior to particle binding, while the NP target cell specificity is increased by a two-step recognition with enzymatic processing and receptor binding.

Small Interfering RNA (siRNA) Therapy Using Kidney Targeting Nanoparticles for Treating Polycystic Kidney Disease

Small Interfering RNA (siRNA) Therapy Using Kidney Targeting Nanoparticles for Treating Polycystic Kidney Disease

Emissive Lipid Nanoparticles as Biophotonic Contrast Agent for Site-Selective Solid Tumor Imaging in Pre-Clinical Models.

Small organic dye-based fluorescent agents are highly potent in solid tumor imaging but face challenges such as poor photostability, nonspecific distribution, low circulation, and weak tumor binding. Nanocarriers overcome these issues with better physicochemical and biological performance, particularly in cancer imaging. Among the various nanosized carriers, lipid formulations are clinically approved but yet to be designed as bright nanocontrast agents for solid tumor diagnosis without affecting surrounding tissues. Herein, indocyanine green (ICG) encapsulated targetable lipid nanoparticles (698 ICG/LNPs) as safe contrast agents (∼200 nm) have been developed and tested for solid tumor imaging and biodistribution. Our findings reveal that nanoprecipitation produces ICG-LNPs with a unique assembly, which contributes to their high brightness with improved quantum yield (3.5%) in aqueous media. The bright, optically stable (30 days) biophotonic agents demonstrate rapid accumulation (within 1 h) and prolonged retention (for up to 168 h) at the primary tumor site, with better signal intensity following a one-time dose administration (17.7 × 109 LNP per dose). Incorporated folic acid (735 folic acid/LNPs) helps in selective tumor binding and the specific biodistribution of intravenously injected nanoparticles without affecting healthy tissues. Designed targetable ICG-LNP (634 MESF) demonstrates high-contrast fluorescence and resolution from the tumor area as compared to the targetable ICG-liposomal nanoparticles (532 MESF). Various in vitro and in vivo findings reveal that the cancer diagnostic efficacy elicited by designed bright lipid nanoparticles are comparable to reported clinically accepted imaging agents. Thus, such LNPs hold translational potential for cancer diagnosis at an early stage.

Targeting nanoparticles to lung cancer-derived A549 cells based on changes on interstitial stiffness in biomimetic models

The mechanical properties and forces of the extracellular environment modulate alveolar epithelial cell behavior. To model cancer/fibrosis associated stiffening and dynamic stretch, a biomimetic device was developed that imitates the active forces in the alveolus, while allowing control over the interstitial matrix stiffness. Alveolar epithelial A549 cancer cells were cultured on the devices and their transcriptome was profiled with RNA sequencing. Pathway analysis showed soft materials upregulated the expression of proteoglycans associated with cancer. Consequently, liposomes were modified with peptides targeting heparan sulfate and chondroitin sulfates of the cell surface glycocalyx. Chondroitin sulfate A targeting improved uptake in cells seeded on stiff biomimetic devices, which is attributed to increased chondroitin sulfate proteoglycan localization on cell surfaces in comparison to cells grown on soft devices. These results demonstrate the critical role that mechanical stiffness and stretch play in the alveolus and the importance of including these properties in nanotherapeutic design.

Functional Ginger-Derived Extracellular Vesicles-Coated ZIF-8 Containing TNF-α siRNA for Ulcerative Colitis Therapy by Modulating Gut Microbiota.

Tumor necrosis factor-α (TNF-α) plays a causal role in the pathogenesis of ulcerative colitis (UC), and anti-TNF-α siRNA shows great promise in UC therapy. However, delivering siRNA with site-targeted stability and therapeutic efficacy is still challenging due to the complex and dynamic intestinal microenvironment. Here, based on the functional plant-derived ginger extracellular vesicles (EVs) and porous ZIF-8 nanoparticles, we propose a novel TNF-α siRNA delivery strategy (EVs@ZIF-8@siRNA) for UC targeted therapy. Ginger EVs show strong colon and macrophage targeting, as well as robust resistance to acidic degradation in the stomach. Moreover, 6-shogaol in ginger-derived EVs displays anti-inflammatory effects, which enhance the treatment efficiency by cooperation with TNF-α siRNA. In vitro experiments reveal that ZIF-8 nanoparticles have high TNF-α siRNA loading capacity and promote siRNA escape from cellular lysosomes. In vivo experiments show that the TNF-α level is reduced more significantly in colonic tissue than other nontargeted inflammation related factors, showing a good targeting of this composite nanoparticle. Furthermore, gut microbiota sequencing results demonstrate that the nanoparticles can promote intestinal barrier repair by regulating the intestinal microbial balance and restoring the intestinal health of UC mice. Therefore, the developed EVs@ZIF-8@siRNA nanoparticles may represent a novel colon-targeted oral drug, providing a promising therapeutic strategy for UC therapy.

Specific peptides targeting the myocardiocyte are prognostic markers for heart attack: Function of α-SMA protein

Myocardial infarction (MI) is a serious cardiovascular disease that often results in a significant decline in heart function and associated complications. α-SMA (α-smooth muscle cell actin) is an important biomarker in the process of cardiac remodeling and repair, and its expression level is closely related to myocardial remodeling and prognosis. Therefore, the purpose of this study was to investigate the potential of nanoparticles containing cardiomyocyte targeting peptides in predicting prognosis and α-SMA protein expression after myocardial infarction, with a view to providing new therapeutic strategies and clinical guidelines. In this study, a novel targeting nanoparticle was constructed, using cardiomyocyte specific peptides as targeting ligands, and characterized by loading different drugs. Subsequently, a mouse model of myocardial infarction was used to systematically evaluate the effect of nanoparticles on α-SMA protein expression and prognosis prediction ability after MI. The expression level of α-SMA was analyzed by Western blot and immunohistochemistry, and the prognosis was evaluated by cardiac function assessment. The study found that nanoparticles containing cardiomyocyte targeting peptides significantly increased α-SMA expression levels and improved heart function in animal models of myocardial infarction. Compared with the control group, the application of targeted nanoparticles was closely related to the level of myocardial cell repair and fibrosis, and could effectively predict the prognosis after myocardial infarction. Therefore, nanoparticles containing cardiomyocyte targeting peptides can not only effectively improve the expression of α-SMA, but also serve as an important prognostic tool after myocardial infarction.

Retracted] Application of a novel targeting nanoparticle contrast agent combined with magnetic resonance imaging in the diagnosis of intraductal papillary mucinous neoplasm.

[This retracts the article DOI: 10.3892/etm.2018.6349.].