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Structure of the liver. a The blood and bile systems of the liver. b The hepatic lobule is a functional and structural unit of the liver. c The hepatic sinusoid is the main area of material exchange in the liver
Source publication
The liver is an important organ in the human body and performs many functions, such as digestion, detoxification, metabolism, immune responses, and vitamin and mineral storage. Therefore, disorders of liver functions triggered by various hepatic diseases, including hepatitis B virus infection, nonalcoholic steatohepatitis, hepatic fibrosis, hepatoc...
Citations
... One of these factors includes the clearance mechanisms in the body. The liver is the largest organ in the reticuloendothelial system (RES) and hence accumulates a notable portion of untargeted NPs (39). While the interaction between Kupffer cell uptake and NP uptake rates at different doses is not well characterized, recent studies have shown that Kupffer cells take up disproportionately larger amounts of NPs when delivered at lower doses because the NP doses fall below a specific threshold (34,40,41). ...
Satisfactory healing following acute tendon injury is marred by fibrosis. Despite the high frequency of tendon injuries and poor outcomes, there are no pharmacological therapies in use to enhance the healing process. Moreover, systemic treatments demonstrate poor tendon homing, limiting the beneficial effects of potential tendon therapeutics. To address this unmet need, we leveraged our existing tendon healing spatial transcriptomics dataset and identified an area enriched for expression of Acp5 (TRAP) and subsequently demonstrated robust TRAP activity in the healing tendon. This unexpected finding allowed us to refine and apply our existing TRAP binding peptide (TBP) functionalized nanoparticle (NP) drug delivery system (DDS) to facilitate improved delivery of systemic treatments to the healing tendon. To demonstrate the translational potential of this DDS, we delivered niclosamide (NEN), an S100a4 inhibitor. While systemic delivery of free NEN did not alter healing, TBP-NP NEN enhanced both functional and mechanical recovery, demonstrating the translational potential of this approach to enhance the tendon healing process.
... Compared with free drugs, nanoparticle-mediated delivery of therapeutics holds great potential to improve the balance between drug efficacy and toxicity. 39,40 Harnessing the advantages of prodrug constitution and nanoassembly, Sengupta et al. rationally engineered PI-103, a PI3K/mTOR inhibitor, into liposomes, to confer systemic injectability and greater therapeutic effects than those of free PI-103. 41 Herein, we identified AZD8055 from a panel of mTORC1/2 blockers as a potent inhibitory agent against liver cancer cells. ...
Background
Hepatocellular carcinoma (HCC) is a highly prevalent and deadly type of cancer, and although pharmacotherapy remains the cornerstone of treatment, therapeutic outcomes are often unsatisfactory. Pharmacological inhibition of mammalian target of rapamycin (mTOR) has been closely associated with HCC regression.
Methods
Herein, we covalently conjugated AZD8055, a potent mTORC1/2 blocker, with a small panel of unsaturated fatty acids via a dynamically activating linkage to enable aqueous self-assembly of prodrug conjugates to form mTOR nanoblockers. Cell-based experiments were carried out to evaluate the effects of the nanoblocker against hepatocellular carcinoma (HCC) cells. The orthotopic and subcutaneous HCC mouse models were established to examine its antitumour activity.
Findings
Among several fatty acids as promoieties, linoleic acid-conjugated self-assembling nanoblocker exhibited optimal size distribution and superior physiochemical properties. Compared with free agents, PEGylated AZD8055 nanoblocker (termed AZD NB) was pharmacokinetically optimized after intravenous administration. In vivo investigations confirmed that AZD NB significantly suppressed tumour outgrowth in subcutaneous HCCLM3 xenograft, Hepatoma-22, and orthotopic Hepa1-6 liver tumour models. Strikingly, treatment with AZD NB, but not free agent, increased intratumour infiltration of IFN-γ⁺CD8⁺ T cells and CD8⁺ memory T cells, suggesting a potential role of the mTOR nanoblocker to remodel the tumour microenvironment. Overall, a single conjugation with fatty acid transformed a hydrophobic mTOR blocker into a systemically injectable nanomedicine, representing a facile and generalizable strategy for improving the therapeutic index of mTOR inhibition-based cancer therapy.
Interpretation
The mTOR inhibition by chemically engineered nanoblocker presented here had enhanced efficacy against tumours compared with the pristine drug and thus has the potential to improve the survival outcomes of patients with HCC. Additionally, this new nanosystem derived from co-assembling of small-molecule prodrug entities can serve as a delivery platform for the synergistic co-administration of distinct pharmaceutical agents.
Funding
This work was supported by the 10.13039/501100001809National Natural Science Foundation of China (32171368,81721091), the 10.13039/501100004731Zhejiang Provincial Natural Science Foundation of China (LZ21H180001), the Jinan Provincial Laboratory Research Project of Microecological Biomedicine (JNL-2022039c and JNL-2022010B), 10.13039/501100011441State Key Laboratory for Diagnosis and Treatment of Infectious Diseases (zz202310), and 10.13039/501100007129Natural Science Foundation of Shandong Province (ZR2023ZD59).
... Polymer-based nanoparticles can also be used to deliver chemotherapy drugs to HCC cells. These nanoparticles are designed to release the drug slowly over time, increasing its effectiveness and reducing toxicity to healthy cells [77]. ...
Hepatocellular carcinoma (HCC) is a common type of liver cancer, with a high mortality rate. Hepatocellular carcinoma is a type of liver cancer that can be effectively managed through early detection and accurate diagnosis, followed by a personalized treatment plan that may include surgical resection, liver transplantation, minimally-invasive techniques, immunotherapy, or targeted therapy depending on the stage and severity of the cancer.
This paper discusses recent advances in the early detection, management, and prevention of HCC. The use of newer imaging techniques, such as Magnetic resonance imaging (MRI) and contrast-enhanced ultrasound, along with image segmentation technology and deep learning models, have greatly enhanced the accuracy of HCC detection and diagnosis. Minimally-invasive techniques, such as thermal ablation and radiofrequency ablation, have allowed for more precise and targeted destruction of tumors, while Nanoparticles, immunotherapy and targeted therapy have shown promise in the management of advanced stage HCC. The use of Artificial intelligence (AI) and machine learning has revolutionized HCC research, aiding in the identification of high-risk patients and predicting outcomes. Lifestyle modifications, such as weight management, alcohol avoidance, and hepatitis B vaccinations, can play a critical role in preventing HCC development.
Recent advances in early detection, management, and prevention of HCC have shown promise in improving patient outcomes. The use of newer imaging techniques, minimally-invasive techniques, immunotherapy, targeted therapy, and AI and machine learning have greatly enhanced HCC research and management, while lifestyle modifications can play a critical role in prevention. However, further research is required to fully understand the potential benefits of nanoparticles, traditional Chinese medicine and herbal medicines in HCC treatment.
... The main characteristic of chitosan is that it is only soluble in acidic media. Chitosan has antimicrobial, antitumor, and immunostimulant properties; however, antimicrobial is the most studied [101]. In addition, according to the study of Hari Sharan Adhikari and Paras Nath Yadav, chitosan can alter the normal mechanism of the cell cycle with enzymatic synthesis and interrupt the hormonal mechanism towards biosynthesis to inhibit the growth of cancer cells. ...
Nanotechnology has emerged as a promising technology in the field of hepatocellular carcinoma (HCC), specifically in the implementation of diagnosis and treatment strategies. Nanotechnology-based approaches, such as nanoparticle-based contrast agents and nanoscale imaging techniques, have shown great potential for enhancing the sensitivity and specificity of HCC detection. These approaches provide high-resolution imaging and allow for the detection of molecular markers and alterations in cellular morphology associated with HCC. In terms of treatment, nanotechnology has revolutionized HCC therapy by enabling targeted drug delivery, enhancing therapeutic efficacy, and minimizing off-target effects. Nanoparticle-based drug carriers can be functionalized with ligands specific to HCC cells, allowing for selective accumulation of therapeutic agents at the tumor site. Furthermore, nanotechnology can facilitate combination therapy by co-encapsulating multiple drugs within a single nanoparticle, allowing for synergistic effects and overcoming drug resistance. This review aims to provide an overview of recent advances in nanotechnology-based approaches for the diagnosis and treatment of HCC. Further research is needed to optimize the design and functionality of nanoparticles, improve their biocompatibility and stability, and evaluate their long-term safety and efficacy. Nonetheless, the integration of nanotechnology in HCC management holds great promise and may lead to improved patient outcomes in the future.
... The literature related to various drug delivery systems developed to treat liver disorders has been discussed in details by other researchers [149]. The authors have pointed out the challenges that limit the clinical translation of this approach includes the following: a) results observed in animal studies were not reproducible in human trials, b) factors such as temperature, ionic strength, biomolecules and pH in bloodstream, c) failure to reach targeted liver cells, d) stimulus dependent release of the drug, and e) insufficient records of safety assessment [150]. ...
The prominent role of gut in regulating the physiology of different organs in a human body is increasingly acknowledged, to which the bidirectional communication between gut and liver is no exception. Liver health is modulated via different key components of gut-liver axis. The gut-derived products mainly generated from dietary components, microbial metabolites, toxins, or other antigens are sensed and transported to the liver through portal vein to which liver responds by secreting bile acids and antibodies. Therefore, maintaining a healthy gut microbiome can promote homeostasis of this gut-liver axis by regulating the intestinal barrier function and reducing the antigenic molecules. Conversely, liver secretions also regulate the gut microbiome composition. Disturbed homeostasis allows luminal antigens to reach liver leading to impaired liver functioning and instigating liver disorders. The perturbations in gut microbiome, permeability, and bile acid pool have been associated with several liver disorders, although precise mechanisms remain largely unresolved. Herein, we discuss functional fingerprints of a healthy gut-liver axis while contemplating mechanistic understanding of pathophysiology of liver diseases and plausible role of gut dysbiosis in different diseased states of liver. Further, novel therapeutic approaches to prevent the severity of liver disorders are discussed in this review.
In this study, we conducted the synthesis of a composite material by grafting an acrylonitrile-co-styrene (AN-co-St) polymer into sodium alginate and incorporating CuO (copper oxide) and TiO2 (titanium dioxide) nanoparticles. The primary objective was to investigate the potential anticancer and antioxidant activities of the composite material. First, CuO and TiO2 nanoparticles were synthesized and characterized for their size, morphology, and surface properties. Subsequently, these nanoparticles were integrated into the sodium alginate matrix, which had been grafted with the AN-co-St polymer, resulting in the formation of the composite material. To confirm successful nanoparticle incorporation and assess the structural integrity of the composite, various techniques such as X-ray diffraction analysis (XRD), scanning electron microscopy-energy dispersive X-ray analysis (SEM-EDX), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA) were employed. The composite material’s anticancer and antioxidant activities were then evaluated. In vitro cell viability assays using the HepG-2 cell line were performed to assess potential cytotoxic effects, while antioxidant (DPPH) assays were conducted to determine the composite’s ability to scavenge free radicals and protect against oxidative stress. Preliminary results indicate that the composite material demonstrated promising anticancer and antioxidant activities. The presence of CuO and TiO2 nanoparticles within the composite contributed to these effects, as these nanoparticles are known to possess anticancer and antioxidant properties. Furthermore, the grafting of the AN-co-St polymer into sodium alginate enhanced the overall performance and stability of the composite material.
Hepatitis B virus (HBV) & hepatitis C virus (HCV) infection is a substantial reason for morbidity and mortality around the world. Chronic hepatitis B (CHB) infection is connected with an enhanced risk of liver cirrhosis, liver decompensation and hepatocellular carcinoma (HCC). Conventional therapy do face certain challenges, for example, poor tolerability and the growth of active resistance. Thus, novel treatment procedures are essential to accomplish the initiation of strong and stable antiviral immune reactions of the individuals. This review explores the current nanotechnology-based carriers for drug and vaccine delivery to treat HBV and HCV.
Hepatocellular carcinoma (HCC) has gradually become a pronoun for terrifying death owing to its high mortality rate. With the progression of HCC, lipid droplets (LDs) in HCC cells exhibit specific variations such as increased LDs number and decreased polarity, which can serve as the diagnostic target. However, developing an effective method to achieve HCC diagnosis and reveal LDs polarity heterogeneity is still a crucial challenge. Herein, the first high‐performance LDs‐targeting probe (1) is reported based on ketocyanine strategy with ultrasensitive polarity‐responding ability and near‐infrared emission. Probe 1 shows excellent sensitivity to polarity parameter Δf (0.027–0.290) with 808‐fold fluorescence enhancement and the emission wavelength red‐shifts 91 nm. In HCC cells, probe 1 shows a 2.5‐ to 5.9‐fold fluorescence enhancement compared with normal and other cancer cells which exceeds clinical threshold of 2.0, indicating probe 1 can distinguish HCC cells. The LDs polarity heterogeneity is revealed and it displays a sequence, HCC cells < other cancer cells < normal cells, which may provide useful insight to engineer LDs‐targeting probes for HCC cell discrimination. Finally, probe 1 realizes accurate HCC diagnosis on the cellular, organ, and in vivo levels, providing a satisfying tool for clinical HCC diagnosis and surgical navigation.
In this era of advanced technology and innovation, infectious diseases still cause significant morbidity and mortality, which need to be addressed. Despite overwhelming success in the development of vaccines, transmittable diseases such as tuberculosis and AIDS remain unprotected, and the treatment is challenging due to frequent mutations of the pathogens. Formulations of new or existing drugs with polymeric materials have been explored as a promising new approach. Variations in shape, size, surface charge, internal morphology, and functionalization position polymer particles as a revolutionary material in healthcare. Here, an overview is provided of major diseases along with statistics on infection and death rates, focusing on polymer-based treatments and modes of action. Key issues are discussed in this review pertaining to current challenges and future perspectives.
Simple Summary
Alcohol-related Liver Disease (ALD) is the leading cause of chronic liver disorders and the first cause of hepatocellular carcinoma in developed countries. Unfortunately, few and poorly efficient therapeutic options are available. Deciphering the molecular mechanisms underlying the development of these diseases is therefore of major interest. MicroRNAs (miRNAs) represent key regulators of gene expression by promoting mRNA decay and/or translation inhibition. Due to their ability to control the expression of many genes involved in metabolism, fibrosis, inflammation, and hepatic carcinogenesis, miRNAs represent potential therapeutic targets. Herein, we discuss the role of miRNAs in the different stages of ALD and their role in the onset of HCC, as well as the potential therapeutic options that could be envisaged.
Abstract
Alcohol-related Liver Disease (ALD) is the primary cause of chronic liver disorders and hepatocellular carcinoma (HCC) development in developed countries and thus represents a major public health concern. Unfortunately, few therapeutic options are available for ALD and HCC, except liver transplantation or tumor resection for HCC. Deciphering the molecular mechanisms underlying the development of these diseases is therefore of major importance to identify early biomarkers and to design efficient therapeutic options. Increasing evidence indicate that epigenetic alterations play a central role in the development of ALD and HCC. Among them, microRNA importantly contribute to the development of this disease by controlling the expression of several genes involved in hepatic metabolism, inflammation, fibrosis, and carcinogenesis at the post-transcriptional level. In this review, we discuss the current knowledge about miRNAs’ functions in the different stages of ALD and their role in the progression toward carcinogenesis. We highlight that each stage of ALD is associated with deregulated miRNAs involved in hepatic carcinogenesis, and thus represent HCC-priming miRNAs. By using in silico approaches, we have uncovered new miRNAs potentially involved in HCC. Finally, we discuss the therapeutic potential of targeting miRNAs for the treatment of these diseases.
