Targeting Capacity Research Articles

Gene-Activating Framework Nucleic Acid-Targeted Upregulating Sirtuin-1 to Modulate Osteoimmune Microenvironment for Diabetic Osteoporosis Therapeutics.

Diabetic osteoporosis, a prevalent chronic complication of diabetes, is marked by reduced bone mass, increased bone fragility, and susceptibility to fractures. A significant cause of this condition is the disruption of osteoblastic homeostasis due to prolonged hyperglycemia, which impedes bone regeneration and remodeling. Despite its prevalence, no effective treatments specifically target diabetic osteoporosis. Recently, small-activating RNA (saRNA) therapy has attracted attention for its targeting capacity, high efficacy, and minimal side effects. However, RNA's inherent properties, such as structural instability, susceptibility to degradation, and poor penetration, limit its applications. To address these limitations, a gene-activating tetrahedral framework nucleic acid (tFNA) with sirtuin-1 (SIRT1) gene activation function is developed, termed Tsa. Tsa exhibits an RNA-protecting effect and can effectively penetrate cell membranes to upregulate SIRT1 gene expression. At the histological level, Tsa treatment alleviates diabetic osteoporosis by increasing bone trabecular density and promoting new bone formation. At the cellular level, it switches macrophage polarization toward the anti-inflammatory M2 phenotype while inhibiting the inflammatory M1 phenotype, creating a favorable bone immune microenvironment for osteoblasts. At the genetic level, Tsa activates SIRT1 expression, which deacetylates Acetyl-p65 to block the NF-κB pathway and restore the osteoimmune environment. Overall, this research demonstrates a nanodrug "Tsa", capable of activating SIRT1 and modulating the bone immune environment, thereby showcasing its immense potential for diabetic osteoporosis treatment.

MMP-2-triggered, mitochondria-targeted PROTAC-PDT therapy of breast cancer and brain metastases inhibition

Proteolytic targeting chimera (PROTAC) technology is a protein-blocking technique and induces antitumor effects, with potential advantages. However, its effect is limited by insufficient distribution and accumulation in tumors. Herein, a transformable nanomedicine (dBET6@CFMPD) with mitochondrial targeting capacity is designed and constructed to combine PROTAC with photodynamic therapy (PDT). In this work, we demonstrate that dBET6@CFMPD exhibits great biodistribution and retention, and can induce potent antitumor response to suppress primary and metastatic tumors, becoming a nanomedicine with potential in cancer combination therapy.

Biomimetic Nanomotors for Deep Ischemia Penetration and Ferroptosis Inhibition in Neuroprotective Therapy of Ischemic Stroke.

Nerve injury represents the primary reason of mortality and disability in ischemic stroke, but effective drug delivery to the region of cerebral ischemia and hypoxia poses a significant challenge in neuroprotective treatment. To address these clinical challenges, a biomimetic nanomotor, Pt@LF is designed, to facilitate deep delivery of neuroprotective agents and inhibit ferroptosis in ischemic stroke. Pt@LF traverses the blood-brain barrier (BBB) and penetrates into deep cerebral ischemic-hypoxic areas due to the active targeting capacity of apo-lactoferrin (Apo-LF) and the self-propelling motion properties of nanomotors. Subsequently, Pt@LF loosens thrombus and alleviates the "no reflow" phenomenon via mechanical thrombolysis. Thanks to the various enzyme-like abilities and multi-target ferroptosis inhibition capability, Pt@LF ameliorates the inflammatory microenvironment and rescues dying neurons. In conclusion, Pt@LF demonstrates efficiently deep penetration and neuroprotective effects in vitro and vivo. And this study provides a promising therapeutic platform for the treatment of ischemic stroke.

Carboxylesterase-activatable multi-in-one nanoplatform for near-infrared fluorescence imaging guided chemo/photodynamic/sonodynamic therapy toward cervical cancer

Traditional tumor treatment faces great challenge owning to inherent drawbacks. Activatable prodrugs with multi-modality therapeutic capacity are highly desired. In this consideration, a responsiveness-released multi-in-one nanoplatform, PLGA-PEG@HC, toward cervical cancer therapy was innovatively developed. Among the nanoplatform, HC was constructed by incorporating chlorambucil, a classic chemotherapy drug into a near-infrared photo- and sono-sensitizer, HCH via ester linker, which can be specifically hydrolyzed by carboxylesterase (CES). HC is scarcely fluorescent and toxic due to the caging of HCH and chlorambucil, thus achieving low background signal and minimal side effects. However, once selectively hydrolyzed by tumor enriched CES, ester bond will be broken. Consequently, HCH and chlorambucil are released so as to achieve near-infrared fluorescence imaging and synergistic photodynamic/sonodynamic/chemo therapy. PLGA-PEG packaging ensures the biocompatibility of HC. The as-obtained nanoplatform, with diameter of 97 nm, achieves tumor targeting capacity via EPR. In vitro and in vivo applications have demonstrated that PLGA-PEG@HC can accumulate in tumor tissues, exhibit CES-activatable near-infrared fluorescence imaging and efficient tumor suppression capacity. Compared with the reported combinational therapy materials which are complex in compositions, PLGA-PEG@HC is simple in formulation but demonstrates near-infrared fluorescence traced and considerable therapy efficacy toward tumors, which may accelerate the clinical translation.

YOLO-APDM: Improved YOLOv8 for Road Target Detection in Infrared Images.

A new algorithm called YOLO-APDM is proposed to address low quality and multi-scale target detection issues in infrared road scenes. The method reconstructs the neck section of the algorithm using the multi-scale attentional feature fusion idea. Based on this reconstruction, the P2 detection layer is established, which optimizes network structure, enhances multi-scale feature fusion performance, and expands the detection network's capacity for multi-scale complicated targets. Replacing YOLOv8's C2f module with C2f-DCNv3 increases the network's ability to focus on the target region while lowering the amount of model parameters. The MSCA mechanism is added after the backbone's SPPF module to improve the model's detection performance by directing the network's detection resources to the major road target detection zone. Experimental results show that on the FLIR_ADAS_v2 dataset retaining eight main categories, using YOLO-APDM compared to YOLOv8n, mAP@0.5 and mAP@0.5:0.95 increased by 6.6% and 5.0%, respectively. On the M3FD dataset, mAP@0.5 and mAP@0.5 increased by 8.1% and 5.9%, respectively. The number of model parameters and model size were reduced by 8.6% and 4.8%, respectively. The design requirements of the high-precision detection of infrared road targets were achieved while considering the requirements of model complexity control.

Spatial feasibility prediction of green hydrogen scale-up in China under decarbonization policies: Based on improved diffusion model

Hydrogen production from renewable electrolysis is a suitable transformative technology for driving a cleaner energy mix, mitigating climate change, and achieving sustainable development and has been given the color value definition of "green hydrogen". However, this low-carbon technology is still in its infancy, and the pathways for expanding market supply have not been analyzed. To address the problems of unclear factors influencing the diffusion of green hydrogen technology innovation, unclear technology diffusion laws, and inaccurate predictions of regional green hydrogen production capacity under the goal of decarbonization policy, this work constructs a spatial assessment framework of the feasibility of low-carbon technology development in response to climate change on the basis of the theory of technological innovation systems, the improved technology diffusion model, and the feasibility of climate change spatial concepts to analyze and predict the diffusion law and regional green hydrogen production capacity of hydrogen production by renewable energy under the goal of carbon neutrality. The results of the study on the development of renewable hydrogen technology in China show that it follows the law of diffusion of low-carbon technologies in both the formation and growth stages. The diffusion of green hydrogen technology in the formation stage is slow, and the regional green hydrogen capacity in the near term cannot meet the decarbonization policy target demand in 2030. Before the spatial inflection point of technology diffusion feasibility, the demand-pull of the phase decarbonization policy target dominated the stability and sustainability of the green hydrogen supply market. After the inflection point, the internal growth of technology diffusion plays a key role in market diffusion and ultimately reaches a saturation value under the joint regulation of policy and the market to realize a carbon-neutral target capacity demand in 2060. The uncertainty of diffusion model parameters leads to anomalies in the feasibility space of technology diffusion, and risks such as overcapacity or insufficient demand in some regions may occur. Overall, this work provides a systematic assessment system for analyzing and predicting the pathways and characteristics of expanding renewable hydrogen production in specific regions under decarbonization policy objectives.

Synthesis of S-alkylated oxadiazole bearing imidazo[2,1-b]thiazole derivatives targeting breast cancer: In vitro cytotoxic evaluation and in vivo radioactive tracing studies

Breast cancer is the most common invasive cancer diagnosed in women, accounting for most cancer-related fatalities globally. Numerous investigations have revealed that breast cancer is characterized by abnormal expression and maintenance of EGFR levels. In terms of structural study and optimization of several EGFR inhibitors, two series of oxadiazole bearing imidazo[2,1-b]thiazole derivatives were designed and synthesized as potential EGFR inhibitors and assessed for their antitumor activity at NCI-USA. Four derivatives 3b, 3c, 3d and 3e elicited remarkable GI% against MDA-MB-468, T-47D and MCF-7 breast cancer cell lines. Thereafter, MTT assay was performed to reveal that compounds 3b (IC50 = 2.27 µM) and 3d (IC50 = 1.46 µM) showed promising cytotoxic activity against MCF-7 and MDA-MB-468 cell lines, respectively, compared to their reference drugs. Compounds 3b, 3d and 3e revealed good selectivity toward tumor cells with reasonable safety profile when tested against the normal cell line MCF-10a. In vitro EGFR inhibitory assay demonstrated that compounds 3b (IC50 = 0.099 µM) and 3d (IC50 = 0.086 µM) exhibited comparable inhibitory activity to the standard drug erlotinib (IC50 = 0.046 µM). A flow cytometric analysis demonstrated that derivatives 3b and 3d arrested the cell cycle at the S phase in MCF-7 and MDB-MB-468, respectively. Furthermore, the most active derivative 3d was subjected to in vivo radioactive studies. In-vivo biodistribution of 99mTc-3d complex showed a notable elevated accumulation in the targeted sarcoma muscle, indicating the targeting capacity of compound 3d in the tumor of sarcoma mice model. The binding mode of compounds 3b and 3d with EGFR was studied by molecular docking and was further inspected by molecular dynamic simulations. Both compounds were shown to be stable during the course of simulation and demonstrated a plausible interaction pattern with the EGFR binding pocket.

Preclinical evaluation of antigen-sensitive B7-H3-targeting nanobody-based CAR-T cells in glioblastoma cautions for on-target, off-tumor toxicity

BackgroundGlioblastoma is the most common lethal primary brain tumor, urging evaluation of new treatment options. Chimeric antigen receptor (CAR)-T cells targeting B7 homolog 3 (B7-H3) are promising because of the...

Engineering PSMA-targeted nanoparticles co-encapsulating mitoxantrone and indocyanine green for precise combinatory therapy in prostate cancer

Prostate cancer is the 2nd most common cancer in men worldwide. Chemotherapeutic treatment of prostate cancer with mitoxantrone (MTX) has limited efficacy due to severe side effects in which cardiotoxicity and myelosuppression are the two major causes of its dose-limiting toxicity. This study aimed to obtain a poly (lactic-co-glycolic acid) (PLGA) nanoparticle that can precisely deliver MTX to the prostate cancer cells overexpressing the Prostate-specific membrane antigen (PSMA) receptor-sparing healthy tissues and co-loading Indocyanine green (ICG) as a fluorescent photothermal/photodynamic agent for precise combinatory therapy in prostate cancer. The biocompatible polymer PLGA was covalently modified with the peptide of sequence (WQPDTAHHWATL) to actively target the PSMA receptor. Factors like the peptide-to-polymer ratio or the peptide's orientation during the polymer's chemical modification were investigated to enhance the active targeting of the nanoparticles (NPs). NPs were characterised using dynamic light scattering, scanning electron microscopy, and UV–vis spectroscopy to determine their morphological and colloidal properties and optimal MTX and ICG encapsulation efficiency. Quantitative FACS analysis of LNCaP and PC-3 cells incubated with Nile Red-labelled non-targeted PLGA or PLGA-PSMA targeted NPs was assessed to identify the best formulation that bound selectively to PSMA. The orientation of the peptide conjugated to the polymer, which has the C-terminal end of the peptide sequence accessible for interaction with the cell receptor, maximises the targeting capacity of the system. Photothermal experiments using 808 nm near-infrared laser irradiation were conducted, and cytotoxicity was assessed using the resazurin viability assay. Remarkably, our results confirmed the safety and efficacy of a targeted and activatable therapy using polymeric NPs functionalised with the peptide and co-loaded with MTX and ICG. This pioneer nanosystem opens new perspectives for exploring advanced targeted delivery in prostate cancer. It offers a straightforward methodology for functionalising drug delivery systems with bioactive peptides that can be applied to different types of cancer.

Release kinetics and protective effect of novel curcumin-based nanoliposome modified with pectin, whey protein isolates and hyaluronic acid against oxidative stress

In the present study, a novel nanoliposome loaded with curcumin (Cur) (NNLs-Cur) was established to overcome the gastrointestinal digestive barrier and enhance mitochondrial targeting capacity, exerting the antioxidant capacity of Cur. Noteworthy, NNLs-Cur was modified by pectin, whey protein isolates and hyaluronic acid. The results showed that the structure of traditional nanoliposomes loaded with Cur (NLs-Cur) was destroyed during digestion. However, NNLs-Cur maintained intact structural morphology, and the release of Cur in the stomach and intestines was consistent with zero-order and first-order kinetic models, respectively. Interestingly, the survival rate of HL-7702 cells after being damaged by H2O2 was 40.53 %, while the survival rate after treated with NNLs-Cur reached 99.87 %. Besides, the fluorescence localization indicated Cur in NNLs-Cur could escape lysosomal and achieve mitochondria targeting. Compared with NLs-Cur, the damaged cells treated with NNLs-Cur increased activities of catalase (CAT), glutathione peroxide (GSH-Px) and superoxide dismutase (SOD) from 16.16 ± 0.52, 16.92 ± 2.28 and 30.10 ± 0.93 U/mgprot to 19.09 ± 0.52, 20.41 ± 1.79 and 33.81 ± 0.29 U/mgprot, respectively. Malondialdehyde (MDA) content and reactive oxygen species (ROS) level of the oxidative damaged cells were reduced, mitochondrial membrane potential was restored, and cell apoptosis was reduced. This study provides theoretical guidance for realizing the industrial application of efficient targeted delivery Cur.

A pH and glutathione-responsive carbon monoxide-driven nano-herb delivery system for enhanced immunotherapy in colorectal cancer

Dihydroartemisinin (DHA), a compound extracted from the herbal medicine Artemisia annua, has shown promise as a clinical treatment strategy for colorectal cancer. However, its clinical use is hindered by its low water solubility and bioavailability. A pH/glutathione (GSH) dual-responsive nano-herb delivery system (PMDC NPs) has been developed for the targeted delivery of DHA, accompanied by abundant carbon monoxide (CO) release. Due to the passive enhanced permeability and retention (EPR) effect and active targeting mediated by pHCT74 peptide binding to overexpressed α-enolase on colorectal cancer cells, the pHCT74/MOF-5@DHA&CORM-401 nanoparticles (PMDC NPs) exhibited specific targeting capacity against colorectal cancer cells. Once reaching the tumor site, the pH/GSH dual-responsive behavior of metal-organic framework-5 (MOF-5) enabled the rapid release of cargo, including DHA and CORM-401, in the acidic tumor microenvironment. Subsequently, DHA stimulated CORM-401 to release CO, which facilitated ROS-induced ferroptosis and apoptosis, leading to immunogenic cell death (ICD) and a sustained antitumor response through the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). Overall, PMDC NPs enhanced the bioavailability of DHA and exhibited outstanding therapeutic effectiveness both in vitro and in vivo, indicating their potential as a promising and feasible alternative for synergistic treatment with immunotherapy and gas therapy in the clinical management of colorectal cancer.

Endothelium-targeted NF-κB siRNA nanogel for magnetic resonance imaging and visualized-anti-inflammation treatment of atherosclerosis

Atherosclerosis-induced lethal cardiovascular disease remains a severe healthcare threat due to the limited drug efficiency and untimely prediction of high-risk events caused by inadequate target specificity of medications, incapable recognition of insensitive patients, and variable morphology of vulnerable plaques. Therefore, it is necessary to develop efficient strategies to improve the diagnosis accuracy and achieve visualized treatment of atherosclerosis. Herein, we establish an inflamed endothelium-targeted three-in-one nucleic acid nanogel system that can reverse the inflammatory state of endothelial cells (ECs) in plaques and simultaneously achieve real-time monitoring of the therapy process for efficient atherosclerosis diagnosis and treatment. For this purpose, contrast agent (Gd-DOTA) and VCAM-1-targeted peptide (VP) are first covalently conjugated onto DNA strands by click reaction respectively, which could self-assemble into Y-shaped structures (Gd-Y1 and VP-Y2 motifs) with magnetic resonance (MR) imaging and endothelium targeting capacities. Thereafter, NF-κB subunit p65-targeting siRNA (siNF-κB) is crosslinked with Gd-Y1 and VP-Y2 motifs to construct the endothelium-targeting nanogel platform. With contrast agents inside, the nanogel enables MR-based diagnosis and visualized therapy of atherosclerosis, providing accurate prognostic analysis and indications for treatment results, which ensures timely disclosure of insensitive individuals and avoids acute lethal events. By delivering siNF-κB to inflammatory endothelium, the nanogel significantly regresses plaques in both the aorta and carotid artery with reduced inflammation cytokines, collagens, macrophages, and apoptotic cells, providing a potential anti-inflammation strategy to treat atherosclerosis and avoid acute cardiovascular disease.

Genome-Wide Profiling of H3K27ac Identifies TDO2 as a Pivotal Therapeutic Target in Metabolic Associated Steatohepatitis Liver Disease.

H3K27ac has been widely recognized as a representative epigenetic marker of active enhancer, while its regulatory mechanisms in pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) remain elusive. Here, a genome-wide comparative study on H3K27ac activities and transcriptome profiling in high fat diet (HFD)-induced MASLD model is performed. A significantly enhanced H3K27ac density with abundant alterations of regulatory transcriptome is observed in MASLD rats. Based on integrative analysis of ChIP-Seq and RNA-Seq, TDO2 is identified as a critical contributor for abnormal lipid accumulation, transcriptionally activated by YY1-promoted H3K27ac. Furthermore, TDO2 depletion effectively protects against hepatic steatosis. In terms of mechanisms, TDO2 activates NF-κB pathway to promote macrophages M1 polarization, representing a crucial event in MASLD progression. A bovine serum albumin nanoparticle is fabricated to provide sustained release of Allopurinol (NPs-Allo) for TDO2 inhibition, possessing excellent biocompatibility and desired targeting capacity. Venous injection of NPs-Allo robustly alleviates HFD-induced metabolic disorders. This study reveals the pivotal role of TDO2 and its underlying mechanisms in pathogenesis of MASLD epigenetically and genetically. Targeting H3K27ac-TDO2-NF-κB axis may provide new insights into the pathogenesis of abnormal lipid accumulation and pave the way for developing novel strategies for MASLD prevention and treatment.

Advance in gold nanoparticle- mediated drug delivery system

Gold nanoparticles (AuNPs) have emerged as versatile platforms for biomedical applications, particularly in cancer research, diagnostics, and therapy. AuNPs exhibit unique optical, electrical, and photothermal properties, making them ideal for sensing, imaging, and targeted therapy. Recent advancements in AuNP synthesis methods, characterization techniques, and applications are highlighted. Various methods, including chemical reduction, green synthesis, and hydrothermal synthesis, can produce AuNPs with controlled sizes and shapes. AuNPs have shown potential in cancer treatment, including ferroptosis induction, drug delivery, and imaging. However, limitations remain concerns. Future directions focus on enhancing stability, biocompatibility, targeting, and drug delivery capacity. AuNP-mediated drug delivery systems offer advantages over traditional medications and other nanocarriers.

A novel HER2 targeting nanoagent self-assembled from affibody-epothilone B conjugate for cancer therapy

Epothilone B (Epo B), a promising antitumor compound effective against various types of cancer cells in vitro. However, its poor selectivity for tumor cells and inadequate therapeutic windows significantly limit its potential clinical application. Affibody is a class of non-immunoglobulin affinity proteins with precise targeting capability to overexpressed molecular receptors on cancer cells, has been intensively investigated due to its exceptional affinity properties. In this study, we present a targeted nanoagent self-assembled from the precursor of an affibody conjugated with Epo B via a linker containing the thioketal (tk) group that is sensitive to reactive oxygen species (ROS). The core-shell structure of the ZHER2:342-Epo B Affibody-Drug Conjugate Nanoagent (Z-E ADCN), with the cytotoxin Epo B encapsulated within the ZHER2:342 affibody corona, leads to significantly reduced side effects on normal organs. Moreover, the abundant presence of ZHER2:342 on the surface effectively enhances the targeting capacity and tumor accumulation of the drug. Z-E ADCN can be internalized by cancer cells via HER2 receptor-mediated endocytosis followed by Epo B release in response to high levels of ROS, resulting in excellent anticancer efficacy in HER2-positive tumor models.

Design optimization of Fucoidan-coating Cationic Liposomes for enhance Gemcitabine delivery.

Obstacles facing chemotherapeutic drugs for cancers led scientists to load Gemcitabine (GEM) into nanocarriers like liposomes, known for their nontoxicity profile and targeting capacity. The liposomal nanostructures containing GEM were coated with Fucoidan (FU) due to its anti-tumor properties by targeting cancer cells. Thus four different cationic liposomes formulations were prepared by thin-film hydration method in optimal conditions: DOTAP (formulation A); DPPC/DOTAP (4:1 molar ratio, formulation B), DPPC/DMPC/DOTAP (4:1:1 molar ratio, formulation C) and DPPC/DMPC/DOTAP/DSPE-mPEG2000 (4:1:1:0.1 molar ratio, formulation D). They were studied to identify lipid-compositions offering effective GEM-entrapment and successful coating of FU on the liposome surface. Additional qualitative characteristics, such as particle size, polydispersity index, zeta potential, stability and in vitro drug release were then evaluated. Formulation C gave the best GEM-entrapment efficiency (EE) but formed aggregates when coated with FU, giving non-homogenous large size particles then not suitable for effective delivery. It was the same situation with formulation A and B. Only the formulation D showed a good GEM-EE (> 80%) and affinity by successful coating FU from three different algae species. The PEGylated formulation D coated of FU, with regard to storage stability and drug release studies, revealed to be a promising approach on design of optimal drug delivery system.

Synergistic metabolism intervention and immune activation for antitumor therapy by biomineralized lactate oxidase

Depleting tumoral lactate is a promising strategy to enhance the immune response and thereby suppressing tumorigenesis. However, the use of lactate oxidase (LOx), the most straightforward lactate-eliminating agent, faces several issues including low stability, no targeting capacity. To solve these problems, a “carrier-free” nanodrug LOx@manganese sulfide (LOx@MnS) was facilely prepared via biomineralization. This way, all the constituents integrated in the nanodrug, including LOx, Mn2+, and hydrogen sulfide (H2S), could be readily delivered into tumor cells and exert their effects. LOx combined with Mn2+ to convert lactate to cytotoxic reactive oxygen species (ROS) through the cascade reaction, meanwhile the crosstalk between H2S and ROS induced metabolism suppression to further augment the therapeutic efficacy. Consequently, the multi-mode modalities evoked by LOx@MnS led to effective induction of immunogenic cell death (ICD) and reversing high-lactate, immunosuppressive microenvironment, suggesting the great potential for anti-tumor immunotherapy. We believe this strategy opens a new avenue to construct functional materials from frangible biomolecules and expand their applications.

Nanoemulsions in Skin Cancer Therapy: A Promising Frontier.

Skin cancer, a global burden for particularly white people, is classified as various histopathological types, including malignant melanoma, basal and squamous cell carcinoma, on the basis of affected different skin layers. Clinical adjuvant therapy (electro-chemotherapy, radio- and immuno therapy), surgical techniques (Cryosurgery, laser treatment, dermabrasion, Moh's micrographic surgery), photodynamic treatment and theranostic approaches are confined only for the treatment of serious health issues. Therefore, nanotechnology based approaches, especially nanoemulsion, a non-spontaneous, transparent or translucent, kinetically stable nanostructured (1-1000nm) colloidal dispersion (comprised of oil, water and surfactant/cosurfactant), are being popularised as a potential topical nanocarrier to deliver BCS class II and IV anti-neoplastic drugs attributing to its capacity for both active and passive tumor targeting in controlled or sustained manner and improving bioavailability via enhancing permeabilityretention effect with minimal adverse effects. Numerous research on nanoemulsion for the treatment of both melanoma and non-melanoma skin cancer is only limited to preclinical stages as several physiological variables reduce the effectiveness of nanoemulsion via restricting topical penetration.

Inhalable cardiac targeting peptide modified nanomedicine prevents pressure overload heart failure in male mice

Heart failure causes considerable morbidity and mortality worldwide. Clinically applied drugs for the treatment of heart failure are still severely limited by poor delivery efficiency to the heart and off-target consumption. Inspired by the high heart delivery efficiency of inhaled drugs, we present an inhalable cardiac-targeting peptide (CTP)-modified calcium phosphate (CaP) nanoparticle for the delivery of TP-10, a selective inhibitor of PDE10A. The CTP modification significantly promotes cardiomyocyte and fibroblast targeting during the pathological state of heart failure in male mice. TP-10 is subsequently released from TP-10@CaP-CTP and effectively attenuates cardiac remodelling and improved cardiac function. In view of these results, a low dosage (2.5 mg/kg/2 days) of inhaled medication exerted good therapeutic effects without causing severe lung injury after long-term treatment. In addition, the mechanism underlying the amelioration of heart failure is investigated, and the results reveal that the therapeutic effects of this system on cardiomyocytes and cardiac fibroblasts are mainly mediated through the cAMP/AMPK and cGMP/PKG signalling pathways. By demonstrating the targeting capacity of CTP and verifying the biosafety of inhalable CaP nanoparticles in the lung, this work provides a perspective for exploring myocardium-targeted therapy and presents a promising clinical strategy for the long-term management of heart failure.

Engineering strategies for apoptotic bodies.

Extracellular vesicles (EVs) are lipid bilayer vesicles containing proteins, lipids, nucleic acids, and metabolites secreted by cells under various physiological and pathological conditions that mediate intercellular communication. The main types of EVs include exosomes, microvesicles, and apoptotic bodies (ABs). ABs are vesicles released during the terminal stages of cellular apoptosis, enriched with diverse biological entities and characterized by distinct morphological features. As a result, ABs possess great potential in fields like disease diagnosis, immunotherapy, regenerative therapy, and drug delivery due to their specificity, targeting capacity, and biocompatibility. However, their therapeutic efficacy is notably heterogeneous, and an overdose can lead to side effects such as accumulation in the liver, spleen, lungs, and gastrointestinal system. Through bioengineering, the properties of ABs can be optimized to enhance drug-loading efficiency, targeting precision, and multifunctionality for clinical implementations. This review focuses on strategies such as transfection, sonication, electroporation, surface engineering, and integration with biomaterials to enable ABs to load cargoes and enhance targeting, providing insights into the engineering of ABs.