Recent advancements of hydrogels in immunotherapy: Breast cancer treatment.

Breast cancer is the most prevalent cancer among women and the leading cause of cancer-related deaths in this population. Recent advances in Immunotherapy, or combined immunotherapy, offering a more targeted and less toxic approach, expand the survival rate of patients more than conventional treatment. Notably, hydrogels, a versatile platform provided promising avenues to combat breast cancer in preclinical studies and extended to clinical practices. With advantages such as the alternation of tumor microenvironment, immunomodulation, targeted delivery of therapeutic agents, and their sustained release at specific sites of interest, hydrogels can potentially be used for the treatment of breast cancer. This review highlights the advantages, mechanisms of action, stimuli-responsiveness properties, and recent advancements of hydrogels for treating breast cancer immunotherapy. Moreover, post-treatment and its clinical translations are discussed in this review. The integration of hydrogels in immunotherapy strategies may pave the way for more effective, personalized, and patient-friendly approaches to combat breast cancer, ultimately contributing to a brighter future for breast cancer patients.

Advances in Radionuclides and Radiolabelled Peptides for Cancer Therapeutics.

Radiopharmaceutical therapy, which can detect and treat tumours simultaneously, was introduced more than 80 years ago, and it has changed medical strategies with respect to cancer. Many radioactive radionuclides have been developed, and functional, molecularly modified radiolabelled peptides have been used to produce biomolecules and therapeutics that are vastly utilised in the field of radio medicine. Since the 1990s, they have smoothly transitioned into clinical application, and as of today, a wide variety of radiolabelled radionuclide derivatives have been examined and evaluated in various studies. Advanced technologies, such as conjugation of functional peptides or incorporation of radionuclides into chelating ligands, have been developed for advanced radiopharmaceutical cancer therapy. New radiolabelled conjugates for targeted radiotherapy have been designed to deliver radiation directly to cancer cells with improved specificity and minimal damage to the surrounding normal tissue. The development of new theragnostic radionuclides, which can be used for both imaging and therapy purposes, allows for more precise targeting and monitoring of the treatment response. The increased use of peptide receptor radionuclide therapy (PRRT) is also important in the targeting of specific receptors which are overexpressed in cancer cells. In this review, we provide insights into the development of radionuclides and functional radiolabelled peptides, give a brief background, and describe their transition into clinical application.

Next-Generation 3D Scaffolds for Nano-Based Chemotherapeutics Delivery and Cancer Treatment.

Cancer is the leading cause of death after cardiovascular disease. Despite significant advances in cancer research over the past few decades, it is almost impossible to cure end-stage cancer patients and bring them to remission. Adverse effects of chemotherapy are mainly caused by the accumulation of chemotherapeutic agents in normal tissues, and drug resistance hinders the potential therapeutic effects and curing of this disease. New drug formulations need to be developed to overcome these problems and increase the therapeutic index of chemotherapeutics. As a chemotherapeutic delivery platform, three-dimensional (3D) scaffolds are an up-and-coming option because they can respond to biological factors, modify their properties accordingly, and promote site-specific chemotherapeutic deliveries in a sustainable and controlled release manner. This review paper focuses on the features and applications of the variety of 3D scaffold-based nano-delivery systems that could be used to improve local cancer therapy by selectively delivering chemotherapeutics to the target sites in future.

Two-photon excitable membrane targeting polyphenolic carbon dots for long-term imaging and pH-responsive chemotherapeutic drug delivery for synergistic tumor therapy.

Long-term dynamic tracking of cells with theranostic properties remains challenging due to the difficulty in preparing and delivering drugs by probes. Herein, we developed highly fluorescent one- and two-photon (OP and TP) excitable polyphenolic carbon quantum dots (CQDs) for excellent membrane-targeting and drug delivery properties for synergistic tumor therapy. The green-emissive CQDs (g-CQDs) were synthesized from a three-fold symmetric polyphenolic molecule, phloroglucinol (C3h; symmetry elements: E, C3, C32, σh, S3, and S3-1), in a sulfuric acid medium. Doxorubicin (Dox) was loaded onto the g-CQDs via electrostatic interaction, resulting in a loading efficiency and content of 54.62% and 323.25 µg mL-1, respectively. The g-CQDs@Dox complex exhibited a higher rate of cell killing efficiency at both pH 5.0 and 6.5, with higher reactive oxygen species (ROS) generation due to the greater Dox accumulation in the tumor cells. In addition, TP cell imaging displayed excellent membrane-targeting properties with less photobleaching ability in tumor cells. The in vivo studies confirmed that the g-CQDs@Dox complex has higher affinity towards tumor cells, better inhibitory effects, and an absence of systemic toxicity. Therefore, our developed nanocarrier exhibited better cell imaging, drug delivery, and tumor-targeting properties, and could be used as a "smart" probe for synergistic tumor therapy.

Graphene: A Promising Theranostic Agent.

Graphene has drawn tremendous interest in the field of nanoscience as a superior theranostic agent owing to its high photostability, aqueous solubility, and low toxicity. This monoatomic thick building block of a carbon allotrope exhibits zero to two-dimensional characteristics with a unique size range within the nanoscale. Their high biocompatibility, quantum yield, and photoluminescent properties make them more demandable in biomedical research. Its application in biomedical sciences has been limited due to its small-scale production. Large-scale production with an easy synthesis process is urgently required to overcome the problem associated with its translational application. Despite all possible drawbacks, the graphene-based drug/gene delivery system is gaining popularity day by day. To date, various studies suggested its application as a theranostic agent for target-specific delivery of chemotherapeutics or antibiotics against various diseases like cancer, Alzheimer's diseases, multidrug resistance diseases, and more. Also, studying the toxicological profile of graphene derivatives is very important before starting its practical use in clinical applications. This chapter has tried to abbreviate several methods and their possible incoming perspective as claimed by researchers for mass production and amplifying graphene-based treatment approaches.

Pharmaceutical Aspects of Nanocarriers for Smart Anticancer Therapy.

Drug delivery to tumor sites using nanotechnology has been demonstrated to overcome the drawbacks of conventional anticancer drugs. Altering the surface shape and geometry of nanocomposites alters their chemical properties, which can confer multiple attributes to nanocarriers for the treatment of cancer and their use as imaging agents for cancer diagnosis. However, heterogeneity and blood flow in human cancer limit the distribution of nanoparticles at the site of tumor tisues. For targeted delivery and controlled release of drug molecules in harsh tumor microenvironments, smart nanocarriers combined with various stimuli-responsive materials have been developed. In this review, we describe nanomaterials for smart anticancer therapy as well as their pharmaceutical aspects including pharmaceutical process, formulation, controlled drug release, drug targetability, and pharmacokinetic or pharmacodynamic profiles of smart nanocarriers. Inorganic or organic-inorganic hybrid nanoplatforms and the electrospinning process have also been briefly described here.

Carboxymethyl Cellulose, Pluronic, and Pullulan-Based Compositions Efficiently Enhance Antiadhesion and Tissue Regeneration Properties without Using Any Drug Molecules.

Pharmacological-based treatment approaches have been used over time to prevent postlaparotomy adhesion. However, the rapid elimination of therapeutics from the peritoneum, and their unwanted side effects, easy flow from the wound site by gravity, and low therapeutic efficacy increase the urgent need for the next generation of antiadhesion agents. This article represents the development of biocompatible and biodegradable antiadhesion agents that consist of carboxymethyl cellulose (CMC) and pullulan with three different types of physical characteristics such as the solution type (ST), film type (FT), and thermosensitive type (TST). These antiadhesion agents that contain no drugs exhibit excellent physical characteristics and superior stability over 30 days in the operative sites without any toxicity and side effects that make the compositions strong candidates as novel antiadhesion agents. Also, the proposed samples reveal superior antiadhesion and tissue regeneration properties in Sprague-Dawley (SD) rats after surgery over Medicurtain. Medicurtain effectively prevented postlaparotomy adhesion in ∼42% of experimental animals, whereas ST 2.25-10, ST 2.5-5, ST 2.5-10, FT 20, and TST 1.5 were effective in 100% of animals. Thus, we believe these antiadhesion agents could be promising to reduce adhesion-related complications during and post-surgical operations and deserve consideration for further study for clinical purposes.

Oral GLP1 Gene Delivery by an Antibody-Guided Nanomaterial to Treat Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic and progressive hyperglycemic condition. Glucagon-like peptide-1 (GLP1) is an incretin secreted from pancreatic ß-cells and helps to produce insulin to balance the blood glucose level without the risk of hypoglycemia. However, the therapeutic application of GLP1 is limited by its intrinsic short half-life and rapid metabolic clearance in the body. To enhance the antidiabetic effect of GLP1, we designed a human cysteine-modified IgG1-Fc antibody-mediated oral gene delivery vehicle, which helps to produce GLP1 sustainably in the target site with the help of increased half-life of the Fc-conjugated nanocarrier, protects GLP1 from acidic and enzymatic degradation in the gastrointestinal (GI) tract, uptakes and transports the GLP1 formulation through the neonatal Fc receptor (FcRn), and helps to release the GLP1 gene in the intestine. Our formulation could reduce the blood glucose from about an average of 320 mg/dL (hyperglycemic) to 150 mg/dL (normal blood glucose concentration) in diabetic mice, which is about 50% reduction of the total blood glucose concentration. GLP1 (500 µg) complexed with the IgG1-Fc carrier was proven to be the optimal dose for a complete reduction of hyperglycemic conditions in diabetic mice. A significant amount of insulin production and the presence of GLP1 peptide were observed in the pancreatic islets of oral GLP1 formulation-treated diabetic mice in immunohistochemistry analysis compared to nontreated diabetic mice. The orally given formulation was completely nontoxic according to the histopathology analysis of mice organ tissues, and no mice death was observed. Our antibody-mediated oral gene delivery system is a promising tool for various oral therapeutic gene delivery applications to treat diseases like diabetes.