Local delivery for Gene Directed Enzyme Prodrug Therapy

Cancer is a significant global socioeconomic burden, as millions of new cases and deaths occur annually. In 2020, almost 10 million cancer deaths were recorded worldwide. Advancements in cancer gene therapy have revolutionized the landscape of cancer treatment. An approach with promising potential for cancer gene therapy is introducing genes to cancer cells that encode for chemotherapy prodrug metabolizing enzymes, such as Cytochrome P450 (CYP) enzymes, which can contribute to the effective elimination of cancer cells. This can be achieved through gene-directed enzyme prodrug therapy (GDEPT). CYP enzymes can be genetically engineered to improve anticancer prodrug conversion to its active metabolites and to minimize chemotherapy side effects by reducing the prodrug dosage. Rational design, directed evolution, and phylogenetic methods are some approaches to developing tailored CYP enzymes for cancer therapy. Here, we provide a compilation of genetic modifications performed on CYP enzymes aiming to build highly efficient therapeutic genes capable of bio-activating different chemotherapeutic prodrugs. Additionally, this review summarizes promising preclinical and clinical trials highlighting engineered CYP enzymes’ potential in GDEPT. Finally, the challenges, limitations, and future directions of using CYP enzymes for GDEPT in cancer gene therapy are discussed.

Oncolytic virotherapy can lead to tumor lysis and systemic anti-tumor immunity, but the therapeutic potential in humans is limited due to the impaired virus replication and the insufficient ability to overcome the immunosuppressive tumor microenvironment (TME). To solve the above problems, we identified that Indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitor Navoximod promoted herpes simplex virus type 1 (HSV-1) replication and HSV-1-mediated oncolysis in tumor cells, making it a promising combination modality with HSV-1-based virotherapy. Thus, we loaded HSV-1 and Navoximod together in an injectable and biocompatible hydrogel (V-Navo@gel) for hepatocellular carcinoma (HCC) virotherapy. The hydrogel formed a local delivery reservoir to maximize the viral replication and distribution at the tumor site with a single-dose injection. Notably, V-Navo@gel improved the disease-free survival time of HCC- bearing mice and protects the mice against tumor recurrence. What’s more, V-Navo@gel also showed an effective therapeutic efficacy in the rabbit orthotopic liver cancer model. Mechanistically, we further discovered that our combination strategy entirely reprogramed the TME through single-cell RNA sequencing. All these results collectively indicated that the combination of Navoximod with HSV-1 could boost the viral replication and reshape TME for tumor eradication through the hydrogel reservoir.

Recent progress in material science has led to the development of new drug delivery systems that go beyond the conventional approaches and offer greater accuracy and convenience in the application of therapeutic agents. This review discusses the evolutionary role of nanocarriers, hydrogels, and bioresponsive polymers that offer enhanced drug release, target accuracy, and bioavailability. Oncology, chronic disease management, and vaccine delivery are some of the applications explored in this paper to show how these materials improve the therapeutic results, counteract multidrug resistance, and allow for sustained and localized treatments.

The packaging is described as a food-grade film predominantly made from algae-based ingredients. It is designed to package and protect products like rice, pasta, ramen, oats, frozen vegetables, and pre-prepared outdoor meals. It can be washed in cold or warm water before use, ‘just like you’d wash a tomato’. Then it can be placed in boiling water, where the film dissolves ‘within a few minutes’ while the food cooks.

While the cellophane wrapper used for Babybel products has reportedly been biobased and home-compostable since late 2020, the Bel Group has undertaken factory trials and real-world validation to develop its paper packaging in line with industrial performance requirements for large-scale production across its global facilities.

Et si le fromage pouvait s’emballer lui-même ? C’est l’idée un peu folle – mais bien réelle – imaginée par Nestlé en collaboration avec l’agence Ogilvy Colombia. Baptisé Self-Packing Cheese, ce projet expérimental transforme un sous-produit laitier souvent jeté, le petit-lait, en un emballage biodégradable capable de protéger… du fromage.

Manger régulièrement de la viande et du poisson a des conséquences écologiques importantes. Les monocultures, la surpêche et l’élevage intensif n’en sont que quelques-unes. Pour y remédier, nous avons pu observer quelques approches innovantes au cours de la dernière décennie, par exemple la viande cultivée, de plus en plus souvent issue d’une imprimante 3D. L’agriculture cellulaire constitue une alternative à l’élevage et peut réduire les émissions de 90 % par rapport à la production de viande bovine. La tendance à ce type d’agriculture est en hausse et la popularité des produits de viande et de poisson cultivés ne cesse de croître. Soutenir les producteurs de ce type d’aliments est l’objectif de sallea. La startup, fondée en novembre 2023, a développé d’échaffaudages innovants imprimés en 3D qui constituent la base de la culture de produits à base de viande et de poisson de n’importe quelle forme et au profil nutritionnel spécifique. De cette manière, il est possible de créer des produits durables sans souffrance animale.

Apparently, the new cellulose-based packaging is used for organic Alpstein mountain cheese and organic Usserrhödler mountain cheese. The cellulose film is said to be free of crude oil-based raw materials and is made from leftover wood from FSC-certified forestry. The packaging aims to preserve taste and guarantee product safety. The new solution has currently been introduced in over 100 stores and is mainly available in German-speaking Switzerland and Ticino.

Little Blossom’s Veggie Sticks - Seaweed & Corn is a snack product for babies and young children that emphasizes natural ingredients and health-conscious consumption. The product is made with 100% natural ingredients, including brown jasmine rice, corn flour, rice bran oil, seaweed powder, corn powder, spices, and yeast extract. It is designed to be suitable for children aged one year and above, offering a crunchy and tasty snack option without added sugar, salt, or preservatives. The Veggie Sticks are Halal Certified and are free from artificial colourings and flavourings. Each serving is conveniently packed in a single-serve portion, making it an ideal on-the-go snack or a healthy addition to a child’s lunchbox.

Cutting out carbs or opting to eat “little and often” are just two examples of nutrition fads that have been hugely popular in recent years. But which fads are rooted in fact? Often, eating healthily is simpler than you think. Below, we spotlight seven commonly held nutrition myths that aren’t actually true.

Help your body, the environment, and animals everywhere with Nurishh plant-based cheese. Our tasty vegan cheese is delicious and contains added vitamins.

High-grade glioma is one of the deadliest primary tumors of the central nervous system. Despite the many novel immunotherapies currently in development, it has been difficult to achieve breakthrough results in clinical studies. The reason may be due to the suppressive tumor microenvironment of gliomas that limits the function of specific immune cells (e.g., T cells) which are currently the primary targets of immunotherapy. However, tumor-associated macrophage, which are enriched in tumors, plays an important role in the development of GBM and is becoming a research hotspot for immunotherapy. This review focuses on current research advances in the use of macrophages as therapeutic targets or therapeutic tools for gliomas, and provides some potential research directions.

The sol–gel chemistry of silica has long been used for manipulating the size, shape, and microstructure of mesoporous silica particles. This manipulation is performed in mild conditions through controlling the hydrolysis and condensation of silicon alkoxide. Compared to amorphous silica particles, the preparation of mesoporous silica, such as MCM-41, using the sol–gel approach offers several unique advantages in the fields of catalysis, medicament, and environment, due to its ordered mesoporous structure, high specific surface area, large pore volume, and easily functionalized surface. In this review, our primary focus is on the latest research related to the manipulation of mesoporous silica architectures using the sol–gel approach. We summarize various structures, including hollow, yolk-shell, multi-shelled hollow, Janus, nanotubular, and 2D membrane structures. Additionally, we survey sol–gel strategies involving the introduction of various functional elements onto the surface of mesoporous silica to enhance its performance. Furthermore, we outline the prospects and challenges associated with mesoporous silica featuring different structures and functions in promising applications, such as high-performance catalysis, biomedicine, wastewater treatment, and CO2 capture.

Most targeted anticancer therapies fail due to drug resistance evolution. Here we show that tumor evolution can be reproducibly redirected to engineer therapeutic opportunity, regardless of the exact ensemble of pre-existing genetic heterogeneity. We develop a selection gene drive system that is stably introduced into cancer cells and is composed of two genes, or switches, that couple an inducible fitness advantage with a shared fitness cost. Using stochastic models of evolutionary dynamics, we identify the design criteria for selection gene drives. We then build prototypes that harness the selective pressure of multiple approved tyrosine kinase inhibitors and employ therapeutic mechanisms as diverse as prodrug catalysis and immune activity induction. We show that selection gene drives can eradicate diverse forms of genetic resistance in vitro.

Mesenchymal stem cells loaded with chemotherapeutic drugs show improved penetration and tumor accumulation. For gene therapy, mesenchymal stem cells can be used as vehicles for suicide genes, the so-called gene-directed enzyme prodrug therapy. Mesenchymal stem cell-based oncolytic viral therapies have been attempted in recent years to enhance the efficacy of infection against the tumor, viral replication, and distribution of viral particles. Many uncertainties remain regarding the function and behavior of mesenchymal stem cells in gliomas. However, strategies to increase mesenchymal stem cell migration to gliomas may improve the delivery of therapeutic agents and enhance their anti-tumor effects, representing promising potential for patient treatment.

Cupffee has designed the ‘world’s first’ edible coffee cup, designed to avoid pollution and reduce CO2 emissions while performing as effectively as its single-use plastic counterparts.

Les personnes atteintes d’Alzheimer oublient souvent de boire… mais raffolent des sucreries. Partant de ce constat, un jeune inventeur a imaginé les Jelly Drops : des bonbons sans sucre composés à 95% d’eau et enrichis en électrolytes. Colorés, ludiques et faciles à consommer, ils permettent aux malades de rester hydratés sans effort, notamment en période de forte chaleur.

Medirest, spécialiste de l’alimentation médicale, dévoile une nouvelle version de Mix&Délices, une solution culinaire dédiée aux personnes souffrant de troubles de la mastication et de la déglutition. Fruit d’un an et demi de recherche et de développement, cette initiative incarne l’alliance réussie entre expertise médicale, scientifique et culinaire.

L’impression 3D est souvent associée aux plastiques et aux métaux, mais aujourd’hui, nous nous intéressons à un domaine bien différent : la nourriture. Certaines imprimantes 3D permettent désormais de créer des sucreries, des pâtisseries, des chocolats et même des plats. Ces appareils offrent une grande liberté et créativité en cuisine, et peuvent, dans certains cas, aider à réduire le gaspillage alimentaire. Bien qu’elles ne remplacent pas encore les fours ou micro-ondes, elles représentent une avancée intéressante pour tous ceux qui aiment cuiciner. Aujourd’hui, nous nous intéressons aux imprimantes 3D alimentaires disponibles à la vente.

Le foie gras, souvent perçu comme le summum de la gastronomie, a toujours été au cœur de nombreuses controverses éthiques. Mais une entreprise australienne de food tech, Vow, réinvente cette délicatesse controversée. Voici Forged Gras : une version de foie gras cultivée en laboratoire qui offre toute la richesse et la douceur du produit traditionnel.

Ce simple geste permet ainsi à Tesco de réduire son empreinte carbone par la même occasion et répond à une demande croissante de solutions plus durables. Cette initiative s’inscrit dans une série d’actions visant à rendre l’industrie alimentaire plus respectueuse de l’environnement.

Depuis 2010 l’innovation alimentaire,du champ à l’assiette,est stimulée par le développement du concept de la FoodTech sur lequel surfent plusieurs milliers de startups. Faut il en attendre de profonds changement dans notre façon de manger ?

Saveggy has received €1.76 million in investments from Unconventional Ventures, LRF Ventures, Almi Invest GreenTech, and industry angels for its edible, plant-based coating – a solution hoped to extend the shelf life of fruits and vegetables.