Therapeutic Substances Research Articles

Convection-enhanced Diffusion: A Novel Tactics to Crack the BBB.

Although the brain is very accessible to nutrition and oxygen, it can be difficult to deliver medications to malignant brain tumours. To get around some of these issues and enable the use of therapeutic pharmacological substances that wouldn't typically cross the blood-brain barrier (BBB), convection-enhanced delivery (CED) has been developed. It is a cutting-edge strategy that gets beyond the blood-brain barrier and enables targeted drug administration to treat different neurological conditions such as brain tumours, Parkinson's disease, and epilepsy. Utilizing pressure gradients to spread the medicine across the target area is the main idea behind this diffusion mechanism. Through one to several catheters positioned stereotactically directly within the tumour mass, around the tumour, or in the cavity created by the resection, drugs are given. This method can be used in a variety of drug classes, including traditional chemotherapeutics and cutting-edge investigational targeted medications by using positive-pressure techniques. The drug delivery volume must be optimized for an effective infusion while minimizing backflow, which causes side effects and lowers therapeutic efficacy. Therefore, this technique provides a promising approach for treating disorders of the central nervous system (CNS).

Innovative Nanoparticle Synthesis and Multifaceted Applications in Medicine and Cancer Therapy

Nanotechnology has far-reaching implications and applications in multiple fields. The biomedical and health sectors can use nanotechnology concepts for medication delivery and treatment. Under controlled conditions, it can target and initiate administering drugs and several other therapeutic agents. Since cancer is the largest cause of death worldwide, prompt diagnosis and effective anticancer treatments are crucial. In this particular context, nanotechnology reduces side effects and directs drug delivery to specifically target cancer cells, providing unique benefits for cancer therapy. In the present thorough review, the most noteworthy new findings for 2010–2023 were compiled, which address the development and use of nanosystems for cancer treatment. Nanoparticles allow precise and controlled release of therapeutic substances at specific action locations, enabling targeted medication delivery. Size, shape, surface, charge, and loading methods impact its efficiency. Researchers have made advancements in encapsulating drugs into nanoliposomes and nanoemulsions, including paclitaxel and fisetin, and are currently testing their suitability in ongoing clinical trials. The purpose of this review is to serve as a continuous path toward recognizing the extraordinary potential of various nanoparticles in cancer therapies.

Models of Hydration Dependent Lymphatic Opening, Interstitial Fluid Flows and Ambipolar Diffusion.

A theoretical understanding of fluid exchange and the role of initial lymph formation in tissues through mathematical/physical modeling is lacking. Here, we present three models for tissues rich in negative fixed charges due to glycosaminoglycans interacting with the extracellular matrix. We first model a lymphatic opening mechanism at relevant hydrations of the interstitium. At each hydration affecting tissue strain, two equations coupled in time are developed and solved with the new lymphatic opening and particle draining mechanism. The lymphatic opening mechanism is then included in a new model of interstitial fluid and macromolecular flow where the influence of different exclusion and available volumes for charged and neutral particles are quantified. For therapeutic interactions with cells, essential differences are found between electrically charged and neutral therapeutic substances. The interstitial fluid hydrostatic pressure gradient and flow are expressed through an extended Darcy equation, derived using similar methods as in kinetic theory of dense gases and fluid flows. Finally, a model for ambipolar diffusion of electrically charged macromolecules in tissue is developed. Our study will inform transport of charged and neutral macromolecules between the vasculature, interstitium, and the lymphatic system, thus having implications for tissue uptake of therapeutic agents.

Wuzi Yanzong Decoction Ameliorates Oligoasthenozoospermia by Up-Regulating Methyltransferase and Increasing Spata, Bcl, and Pik3 Series Genes Methylation Level.

Wuzi Yanzong decoction (WZYZD) belongs to the traditional formula for treating male infertility caused by oligoasthenozoospermia (OLI). This research aims to elucidate the therapeutic substance basis and potential pharmacological mechanisms of WZYZD in treating OLI. A total of 52 chemical ingredients were identified from WZYZD. HE and TUNEL staining demonstrated that WZYZD can markedly alleviate OLI. Immunofluorescence analysis showed that WZYZD can significantly increase the expression levels of DNMT3 A, PIWIL1, SETDB1, and PRMT5. Methyl capture sequencing proved that WZYZD can markedly upregulate the methylated level of Spata, Bcl, and Pik3 series genes. Network pharmacology analysis proved that WZYZD can ameliorate OLI through BCL-2 and PI3 K-AKT signaling pathways. The immunofluorescence assay of BCL-2 and SPATA18 proved the aforementioned results. The potential mechanism of WZYZD in treating OLI mainly involved recruiting methyltransferase DNMT3 A, PIWIL1, PRMT5, and SETDB1 and increasing the methylation degree of Spata, Bcl, and Pik3 series genes.

EXTH-05. STEM CELL-BASED THERAPEUTIC STRATEGY FOR LEPTOMENINGEAL METASTASIS OF SOLID CANCERS

Abstract Leptomeningeal dissemination (LMD), known as carcinomatous meningitis, presents an extremely poor prognosis with an average life expectancy of 4-6 weeks. Although whole brain/spinal cord irradiation and intrathecal injection of anticancer drugs are sometimes performed, their effects are limited, so new therapeutic strategies for LMD are urgently needed. Based on the following greatest advantage of stem cell (SC) based therapeutic strategy for LMD, we tested its efficacy in LMD of various solid cancers; LMD is a condition in which cancer cells spread within a huge single space without separation, and the SCs with the characteristic of cancer tropism and chemotaxis can reach cancer cells easily; Repetitive intrathecal injection of therapeutic agents for patients is an invasive and risky procedure, but SCs can continuously secrete/release therapeutic agents into the cerebrospinal fluid after a few injections and increase local concentration of therapeutic substances. We have shown that treatment using engineered SCs may be effective treatment option against LMD from breast cancer, lung cancer, and malignant melanoma. Specifically, we reported that engineered allogeneic SCs which simultaneously targeting epidermal growth factor receptor (EGFR) and death receptor (DR) has efficacy for LMD of triple negative breast cancer and non-small cell lung cancer. Also, we reported that SCs releasing oncolytic herpes virus, granulocyte-macrophage colony-stimulating factor (GM-CSF), and single-chain variable region fragments (scFv) against programmed death receptor-1 (PD-1) has efficacy in LMD of malignant melanoma. Overall, we believe that SC therapy has the potential to become a new therapeutic option for LMD in the future.

Bioaccumulation and tissue distribution of pharmaceuticals and their transformation products in fish along the pollution gradients of a wastewater-impacted river

A field study on the occurrence and distribution of forty-three pharmaceutically active compounds (PhACs) in water and fish samples from anthropogenically impacted section of the Sava River (Croatia) was performed to estimate the importance of bioaccumulation for the environmental risk assessment of PhACs. The study was performed using a highly specific LC-MS/MS method, tailored to include the most prominent PhACs from different therapeutic categories as well as their major metabolites and/or transformation products (TPs). The results revealed a widespread occurrence of PhAC residues both in water and fish samples with a large spatial variability reflecting the distance from the dominant wastewater discharges. The most prominent PhAC categories in less polluted upstream part of the river were common psychostimulants caffeine and cotinine, therapeutic opioids and cardiovascular drugs, while in the river section affected by the local municipal and industrial wastewater inputs, antibiotic drugs became clearly predominant, especially in fish tissue samples. The apparent bioconcentration factors (BCFs) of investigated PhACs varied over several orders of magnitude, from 0.02 ± 0.01 L kg−1 for O-desmethyl tramadol in fish muscle to 784 ± 260 L kg−1 for terbinafine in fish liver, indicating rather large differences in their bioconcentration potential and affinity to different tissues, with the tissue-specific BCFs increasing in the following order: muscle < gills < gonads < heart < liver < kidneys. The bioconcentration potential of most of the PhACs included in this study was only low to moderate however moderately high BCFs of certain PhACs (e.g. sertraline, terbinafine, loratadine, diazepam and azithromycin) in some tissues should be taken into consideration when assessing their potential environmental risks. Moreover, it was shown that BCFs could be strongly affected by biotransformation in fish. Risk prioritization based on risk quotient (RQ) and ToxPi index, revealed antibiotics, in particular azithromycin, and therapeutic psychoactive substances as the most hazardous pharmaceutical contaminants in the Sava River.

Antiviral Effect of Melatonin on Caco-2 Cell Organoid Culture: Trick or Treat?

Melatonin is a hormone naturally produced by the body that has recently been found to have antiviral properties. However, its antiviral mechanisms are not entirely understood. Using Caco-2 cells, we developed a gastrointestinal organoid model to investigate the impact of melatonin on cellular organoid culture response to Poly I:C-induced viral inflammation in the gastrointestinal tract. Melatonin was found to have different effect when applied as a pretreatment before the induction of viral inflammation or as a treatment after it. Melatonin pretreatment after Poly I:C stimulation did not protect organoids from size reduction but enhanced cell proliferation, especially when lower (1 and 10 µM) melatonin concentrations were used. On the other hand, treatment with melatonin after the induction of viral inflammation helped to maintain the size of the organoids while reducing cell proliferation. In pretreated cells, reduced IFNLR1 expression was found, while melatonin treatment increased IFNLR1 expression and reduced the production of viral cytokines, such as IFNλ1 and STAT1-3, but did not prevent from apoptosis. The findings of this study emphasize the importance of type III IFNs in antiviral defense in epithelial gastrointestinal cells and shed more light on the antiviral properties of melatonin as a potential therapeutic substance.

Administration Route Differentiation of Altrenogest via the Metabolomic LC-HRMS Analysis of Equine Urine.

Altrenogest, also known as allyltrenbolone, is a synthetic form of progesterone used therapeutically to suppress unwanted symptoms of estrus in female horses. Altrenogest affects the system by decreasing levels of endogenous gonadotrophin and luteinizing and follicle-stimulating hormones, which in turn decreases estrogen and mimics the increase of progesterone production. This results in more manageable mares for training and competition alongside male horses while improving the workplace safety of riders and handlers. However, when altrenogest is administered, prohibited steroid impurities such as trendione, trenbolone, and epitrenbolone can be detected. It has been assumed that greater concentrations of these steroid impurities are present in injectable preparations and, therefore, pose a greater risk of causing anabolic effects when administered. For this reason, and due to the necessity of this therapeutic substance for the safety of thoroughbred racing participants, a metabolomic approach investigating the differentiation of two main administration routes was conducted. Liquid chromatography high-resolution mass spectrometry analysis of equine urine samples found five sulfated compounds, estrone sulfate, testosterone sulfate, 2-methoxyestradiol sulfate, pregnenolone sulfate, and cortisol sulfate, with the potential to differentiate between oral and intramuscularly administered altrenogest using a random forest classification model. The best model results, comparing two horses' administration normalized peak area datasets, gave an AUC score of 0.965 with a confidence level of 95% (between 0.931 and 0.995). Identifications of these compounds were confirmed with assistance from the Shimadzu Insight Explore Assign feature, together with MS/MS spectrum and retention time matching of purchased and synthesized reference standards. This study proposes a new potential application for metabolomic multi-tool workflows and machine learning models in a forensic toxicological context.

A Review on Film Forming Spray Technology in Wound Management

Purpose: Skin is an important delivery channel for medications, providing both local and systemic effects. One kind of novel medication delivery technology that is administered topically to the skin is called a topical film forming system. The thorough analysis examines how film-forming sprays have revolutionized a variety of fields, including wound care and medicine. The goal is to present a thorough summary of the assessment criteria, composition, and most recent advancements in film-forming sprays intended for wound healing. Methods: The evaluation parameters including film formation, morphology, flexibility, drying time, pH, viscosity, skin irritation, water washability, bioadhesive strength, and container-related evaluations are provided in a systematic manner for film-forming sprays. The review presents findings from a range of research publications that demonstrate various approaches and strategies used to evaluate the properties and effectiveness of film-forming spray formulations. Results: Examples from current research are given to show the variety of uses for film-forming sprays in wound healing. Formulations containing human epidermal growth factor (hEGF) and water- soluble chitosan, propolis from stingless bees, and a complexed polymer film-forming spray for diabetic wound dressing are among the research offerings. In terms of stability, wound closure acceleration, and regulated distribution of therapeutic substances, these formulations show encouraging results. Conclusion: The review concludes that film-forming sprays represent a promising avenue in advanced wound care, offering advantages such as enhanced flexibility, prolonged adherence, and controlled drug delivery.

Applications of Metal-Organic Frameworks (MOFs) in Drug Delivery, Biosensing, and Therapy: A Comprehensive Review.

The porous materials known as metal-organic frameworks (MOFs) stand out for their enormous surface area, adaptable pore size and shape, and structural variety. These characteristics make them well-suited for various applications, especially in healthcare. This review thoroughly summarizes recent studies on the use of MOFs in drug delivery, biosensing, and therapeutics. MOFs may encapsulate medications, target certain cells or tissues, and regulate their release over time. Additionally, MOFs have the potential to be used in biosensing applications, allowing for the selective detection of chemical and biological substances. MOFs' optical or electrical characteristics may be modified to make biosensors that track physiological data. MOFs show potential for targeted drug delivery and the regulated release of therapeutic substances in cancer treatment. In addition, they may work as potent antibacterial agents, providing a less dangerous option than traditional antibiotics that increase antibiotic resistance. For practical applications, further research is required as well as more consideration for the problems with toxicity and biocompatibility. In addition to addressing the difficulties and promising possibilities in this area, this study intends to provide insights into the potential of MOFs in healthcare for drug delivery, biosensing, and treatment. Despite several essential reviews in this area, it was necessary to look into the most recent research on drug delivery, biosensing, and therapy as a combined concept.

Focused Insights into Liposomal Nanotherapeutics for Antimicrobial Treatment.

Addressing infectious conditions presents a formidable challenge, primarily due to the escalating issue of bacterial resistance. This, coupled with limited financial resources and stagnant antibiotic research, compounds the antibiotic crisis. Innovative strategies, including novel antibiotic development and alternative solutions, are crucial to combat microbial resistance. Nanotherapeutics offers a promising approach to enhance drug delivery systems. Integration into lipid-based nanoscale delivery systems, particularly through therapeutic substance encapsulation in liposomal carriers, significantly prolongs drug presence at infection sites. This not only reduces toxicity but also shields antibiotics from degradation. Lipidic carriers, particularly liposomes, exhibit remarkable specificity in targeting infectious cells. This holds great promise in combating antimicrobial resistance and potentially transforming treatment for multi-drug resistant infections. Leveraging liposomal carriers may lead to breakthroughs in addressing drugresistant bacterial infections. This review emphasizes the potential of antimicrobial-loaded liposomes as a novel delivery system for bacterial infections. Encapsulating antimicrobial agents within liposomes enhances treatment efficiency. Moreover, liposomal systems counteract challenges posed by antimicrobial resistance, offering hope in managing persistent multidrug-resistant infections. In the battle against bacterial resistance and the antibiotics crisis, the use of antimicrobial-loaded liposomes as delivery vehicles shows great promise. This innovative approach not only extends drug effectiveness and reduces toxicity but also provides a path to address highly resistant infectious conditions. As research advances, liposomal nanotherapeutics may emerge as a transformative solution in the fight against bacterial infections.

Interleukin-12 Delivery Strategies and Advances in Tumor Immunotherapy.

Interleukin-12 (IL-12) is considered to be a promising cytokine for enhancing an antitumor immune response; however, recombinant IL-12 has shown significant toxicity and limited efficacy in early clinical trials. Recently, many strategies for delivering IL-12 to tumor tissues have been developed, such as modifying IL-12, utilizing viral vectors, non-viral vectors, and cellular vectors. Previous studies have found that the fusion of IL-12 with extracellular matrix proteins, collagen, and immune factors is a way to enhance its therapeutic potential. In addition, studies have demonstrated that viral vectors are a good platform, and a variety of viruses such as oncolytic viruses, adenoviruses, and poxviruses have been used to deliver IL-12-with testing previously conducted in various cancer models. The local expression of IL-12 in tumors based on viral delivery avoids systemic toxicity while inducing effective antitumor immunity and acting synergistically with other therapies without compromising safety. In addition, lipid nanoparticles are currently considered to be the most mature drug delivery system. Moreover, cells are also considered to be drug carriers because they can effectively deliver therapeutic substances to tumors. In this article, we will systematically discuss the anti-tumor effects of IL-12 on its own or in combination with other therapies based on different delivery strategies.

Effects of Chitosan and N-Succinyl Chitosan on Metabolic Disorders Caused by Oral Administration of Olanzapine in Mice.

The issue of human mental health is gaining more and more attention nowadays. However, most mental disorders are treated with antipsychotic drugs that cause weight gain and metabolic disorders, which include olanzapine (OLZ). The search for and development of natural compounds for the prevention of obesity when taking antipsychotic drugs is an urgent task. The biopolymer chitosan (Chi) and its derivatives have lipid-lowering and anti-diabetic properties, which makes them potential therapeutic substances for use in the treatment of metabolic disorders. The purpose of this work was to analyze the effect of the natural biopolymer Chi, its derivative N-succinyl chitosan (SuChi), and Orlistat (ORL) as a control on the effects caused by the intake of OLZ in a mouse model. Mice were fed with pearl barley porridge mixed with OLZ or combinations OLZ + Chi, OLZ + SuChi, or OLZ + ORL for 2 months. The weight, lipid profile, blood chemokines, expression of genes associated with appetite regulation, and behavior of the mice were analyzed in dynamics. For the first time, data were obtained on the effects of Chi and SuChi on metabolic changes during the co-administration of antipsychotics. Oral OLZ increased body weight, food and water intake, and glucose, triglyceride, and cholesterol levels in blood. ORL and SuChi better normalized lipid metabolism than Chi, decreasing triglyceride and cholesterol levels. OLZ decreased the production of all chemokines tested at the 4th week of treatment and increased CXCL1, CXCL13, and CCL22 chemokine levels at the 7th week. All of the supplements corrected the level of CXCL1, CXCL13, and CCL22 chemokines but did not recover suppressed chemokines. SuChi and ORL stimulated the expression of satiety associated proopiomelanocortin (POMC) and suppressed the appetite-stimulating Agouti-related protein (AgRP) genes. All supplements improved the locomotion of mice. Taken collectively, we found that SuChi more than Chi possessed an activity close to that of ORL, preventing metabolic disorders in mice fed with OLZ. As OLZ carries positive charge and SuChi is negatively charged, we hypothesized that SuChi's protective effect can be explained by electrostatic interaction between OLZ byproducts and SuChi in the gastrointestinal tract.

Nanosonosensitizer Optimization for Enhanced Sonodynamic Disease Treatment.

Low-intensity ultrasound-mediated sonodynamic therapy (SDT), which, by design, integrates sonosensitizers and molecular oxygen to generate therapeutic substances (e.g., toxic hydroxyl radicals, superoxide anions, or singlet oxygen) at disease sites, has shown enormous potential for the effective treatment of a variety of diseases. Nanoscale sonosensitizers play a crucial role in the SDT process because their structural, compositional, physicochemical, and biological characteristics are key determinants of therapeutic efficacy. In particular, advances in materials science and nanotechnology have invigorated a series of optimization strategies for augmenting the therapeutic efficacy of nanosonosensitizers. This comprehensive review systematically summarizes, discusses, and highlights state-of-the-art studies on the current achievements of nanosonosensitizer optimization in enhanced sonodynamic disease treatment, with an emphasis on the general design principles of nanosonosensitizers and their optimization strategies, mainly including organic and inorganic nanosonosensitizers. Additionally, recent advancements in optimized nanosonosensitizers for therapeutic applications aimed at treating various diseases, such as cancer, bacterial infections, atherosclerosis, and autoimmune diseases, are clarified in detail. Furthermore, the biological effects of the improved nanosonosensitizers for versatile SDT applications are thoroughly discussed. The review concludes by highlighting the current challenges and future opportunities in this rapidly evolving research field to expedite its practical clinical translation and application.

Implementing Optogenetic-Controlled Bacterial Systems in Drosophila melanogaster for Alleviation of Heavy Metal Poisoning.

Drosophila melanogaster (fruit fly) is an animal model chassis in biological and genetic research owing to its short life cycle, ease of cultivation, and acceptability to genetic modification. While the D. melanogaster chassis offers valuable insights into drug efficacy, toxicity, and mechanisms, several obvious challenges such as dosage control and drug resistance still limit its utility in pharmacological studies. Our research combines optogenetic control with engineered gut bacteria to facilitate the precise delivery of therapeutic substances in D. melanogaster for biomedical research. We have shown that the engineered bacteria can be orally administered to D. melanogaster to get a stable density of approximately 28,000 CFUs/per fly, leading to no detectable negative effects on the growth of D. melanogaster. In a model of D. melanogaster exposure to heavy metal, these orally administered bacteria uniformly express target genes under green light control to produce MtnB protein for binding and detoxifying lead, which significantly reduces the level of oxidative stress in the intestinal tract of Pb-treated flies. This pioneering study lays the groundwork for using optogenetic-controlled bacteria in the model chassis D. melanogaster to advance biomedical applications.

Exploring Potential Aquaculture-Immunostimulant-Peptides Derived from Chlorella sorokiniana

Chlorella sorokiniana is a microalgae with an outstanding nutritional profile and numerous therapeutic substances that can be used as an immunostimulant, including in aquaculture. This research aimed to investigate and characterize peptides isolated from C. sorokiniana protein using TCA digestion and hydrolyzed enzymatically with trypsin. Peptides were then subsequently identified using Tandem LC-MS/MS and Mascot Distiller. Results showed that the percentage of pure protein yield following TCA digestion was 54.66%, and 12 peptides with lengths ranging from 7 to 23 sequences were discovered after trypsin digestion. These peptides originated from various enzymes and chloroplast proteins, including protein synthesis elongation factor TU, photosystem I iron-sulfur center, photosystem II 43 kDa, Ycf4, ATP-dependent zinc metalloprotease FtsH homolog, nitrate reductase, chloroplastic glucose-6-phospate dehydrogenase, and ATP synthase CF1 alpha chain. These findings demonstrated that C. sorokiniana might serve as a source of immunostimulant peptides and proteins, particularly for aquaculture biota.

Potential of Dendrimers in Drug Delivery: An Updated Review

Dendrimers have become a choice, for delivering drugs at the nano level thanks to their structure that allows precise control over size, shape, and surface features. This summary gives an update on progress in using dendrimers for drug delivery. To start with it talks about the ways dendrimers are customized for drug delivery needs like modifying their surfaces to make them more compatible with the body and targeting specific delivery sites. By adding elements that respond to conditions like pH or temperature they can release drugs in a controlled manner when needed. The summary also looks at developments using dendrimer-based formulations for types of therapeutic substances such as small molecules, peptides, proteins, and genetic material. These formulations have shown performance in how drugs move through the body, effectiveness in treating illnesses, and fewer side effects compared to methods of drug delivery. It also covers studies done before applying these systems in real-life blood-brain situations and how they could help get past barriers within the body like the blood-brain barrier or deliver drugs directly to tissues or cells - improving treatments while reducing overall harm. Lastly, it touches on obstacles and future paths, for research involving dendrimers like making them more scalable and consistent well as meeting regulatory standards. It is essential to overcome these obstacles to successfully transition dendrimer-based drug delivery systems, from research labs to use thereby harnessing their capabilities to transform drug delivery and personalized medicine.

Polyethylene Glycol/Pullulan-Based Carrier for Silymarin Delivery and Its Potential in Biomedical Applications.

Restoring the structures and functions of tissues along with organs in human bodies is a topic gathering attention nowadays. These issues are widely discussed in the context of regenerative medicine. Excipients/delivery systems play a key role in this topic, guaranteeing a positive impact on the effectiveness of the drugs or therapeutic substances supplied. Advances in materials engineering, particularly in the development of hydrogel biomaterials, have influenced the idea of creating an innovative material that could serve as a carrier for active substances while ensuring biocompatibility and meeting all the stringent requirements imposed on medical materials. This work presents the preparation of a natural polymeric material based on pullulan modified with silymarin, which belongs to the group of flavonoids and derives from a plant called Silybum marianum. Under UV light, matrices with a previously prepared composition were crosslinked. Before proceeding to the next stage of the research, the purity of the composition of the matrices was checked using Fourier-transform infrared (FT-IR) spectroscopy. Incubation tests lasting 19 days were carried out using incubation fluids such as simulated body fluid (SBF), Ringer's solution, and artificial saliva. Changes in pH, electrolytic conductivity, and weight were observed and then used to determine the sorption capacity. During incubation, SBF proved to be the most stable fluid, with a pH level of 7.6-7.8. Sorption tests showed a high sorption capacity of samples incubated in both Ringer's solution and artificial saliva (approximately 350%) and SBF (approximately 300%). After incubation, the surface morphology was analyzed using an optical microscope for samples demonstrating the greatest changes over time. The active substance, silymarin, was released using a water bath, and then the antioxidant capacity was determined using the Folin-Ciocâlteu test. The tests carried out proved that the material produced is active and harmless, which was shown by the incubation analysis. The continuous release of the active ingredient increases the biological value of the biomaterial. The material requires further research, including a more detailed assessment of its balance; however, it demonstrates promising potential for further experiments.

Engineering PEG10assembled endogenous virus-like particles with genetically encoded neoantigen peptides for cancer vaccination.

Tumor neoantigen peptide vaccines hold potential for boosting cancer immunotherapy, yet efficiently co-delivering peptides and adjuvants to antigen-presenting cells in vivo remains challenging. Virus-like particle (VLP), which is a kind of multiprotein structure organized as virus, can deliver therapeutic substances into cells and stimulate immune response. However, the weak targeted delivery of VLP in vivo and its susceptibility to neutralization by antibodies hinder their clinical applications. Here, we first designed a novel protein carrier using the mammalian-derived capsid protein PEG10, which can self-assemble into endogenous VLP (eVLP) with high protein loading and transfection efficiency. Then, an engineered tumor vaccine, named ePAC, was developed by packaging genetically encoded neoantigen into eVLP with further modification of CpG-ODN on its surface to serve as an adjuvant and targeting unit to dendritic cells (DCs). Significantly, ePAC can efficiently target and transport neoantigens to DCs, and promote DCs maturation to induce neoantigen-specific T cells. Moreover, in mouse orthotopic liver cancer and humanized mouse tumor models, ePAC combined with anti-TIM-3 exhibited remarkable antitumor efficacy. Overall, these results support that ePAC could be safely utilized as cancer vaccines for antitumor therapy, showing significant potential for clinical translation.

Engineering PEG10-assembled endogenous virus-like particles with genetically encoded neoantigen peptides for cancer vaccination

Tumor neoantigen peptide vaccines hold potential for boosting cancer immunotherapy, yet efficiently co-delivering peptides and adjuvants to antigen-presenting cells in vivo remains challenging. Virus-like particle (VLP), which is a kind of multiprotein structure organized as virus, can deliver therapeutic substances into cells and stimulate immune response. However, the weak targeted delivery of VLP in vivo and its susceptibility to neutralization by antibodies hinder their clinical applications. Here, we first designed a novel protein carrier using the mammalian-derived capsid protein PEG10, which can self-assemble into endogenous VLP (eVLP) with high protein loading and transfection efficiency. Then, an engineered tumor vaccine, named ePAC, was developed by packaging genetically encoded neoantigen into eVLP with further modification of CpG-ODN on its surface to serve as an adjuvant and targeting unit to dendritic cells (DCs). Significantly, ePAC can efficiently target and transport neoantigens to DCs, and promote DCs maturation to induce neoantigen-specific T cells. Moreover, in mouse orthotopic liver cancer and humanized mouse tumor models, ePAC combined with anti-TIM-3 exhibited remarkable antitumor efficacy. Overall, these results support that ePAC could be safely utilized as cancer vaccines for antitumor therapy, showing significant potential for clinical translation.