Preparation and characterization of PVA/chitosan nanofibers loaded with Dragon's blood or poly helixan as wound dressings.

Nanofibers have been investigated in regenerative medicine. Dragon's blood (DB)- and poly helixan PF (PHPF) are natural materials used in cosmetics. Herein, we generated DB- and PHPF-loaded polyvinyl alcohol/chitosan (PVA/CS/DB and PVA/CS/PHPF, respectively) nanofibers. PVA/CS/DB and PVA/CS/PHPF nanofibers had an average diameter of 547.5 ± 17.13 and 521 ± 24.67 nm, respectively as assessed by SEM, and a degradation rate of 43.1 and 47.6 % after 14 days, respectively. PVA/CS/DB and PVA/CS/PHPF nanofibers had a hemolysis rate of 0.10 and 0.39 %, respectively, and a water vapor transmission rate of ∼2200 g.m-2.day-1. These nanofibers exhibited favorable antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis in vitro. PVA/CS/DB and PVA/CS/PHPF nanofibers demonstrated a sustained release of 77.91 and 76.55 % over 72 h. PVA/CS/DB and PVA/CS/PHPF nanofibers had a high rate of cytocompatibility and significantly improved the viability of NIH/3T3 cells as compared with free drugs or unloaded nanofibers. Histological inspection via H&E and Verhoeff's staining demonstrated PVA/CS/DB and PVA/CS/PHPF nanofibers enhanced the wound healing and damaged tissue recovery of unsplinted wound models by promoting epithelial layer formation, collagen deposition, and enhancing the presence of fibroblasts. Conclusively, PVA/CS/DB and PVA/CS/PHPF can be introduced as potential wound dressing candidates with favorable properties.

Comparison of the protective effects of CS/TPP and CS/HPMCP nanoparticles containing berberine in ethanol-induced hepatotoxicity in rat.

BACKGROUND: Alcoholic liver disease (ALD) is a globally critical condition with no available efficient treatments. METHODS: Herein, we generated chitosan (CS) nanoparticles cross-linked with two different agents, hydroxypropyl methylcellulose phthalate (HPMCP; termed as CS/HPMCP) and tripolyphosphate (TPP; termed as CS/TPP), and loaded them with berberine (BBr; referred to as CS/HPMCP/BBr and CS/TPP/BBr, respectively). Alongside the encapsulation efficiency (EE) and loading capacity (LC), the releasing activity of the nanoparticles was also measured in stimulated gastric fluid (SGF) and stimulated intestinal fluid (SIF) conditions. The effects of the prepared nanoparticles on the viability of mesenchymal stem cells (MSCs) were also evaluated. Ultimately, the protective effects of the nanoparticles were investigated in ALD mouse models. RESULTS: SEM images demonstrated that CS/HPMCP and CS/TPP nanoparticles had an average size of 235.5 ± 42 and 172 ± 21 nm, respectively. The LC and EE for CS/HPMCP/BBr were calculated as 79.78% and 75.79%, respectively; while the LC and EE for CS/TPP/BBr were 84.26% and 80.05%, respectively. pH was a determining factor for releasing BBr from CS/HPMCP nanoparticles as a higher cargo-releasing rate was observed in a less acidic environment. Both the BBr-loaded nanoparticles increased the viability of MSCs in comparison with their BBr-free counterparts. In vivo results demonstrated CS/HPMCP/BBr and CS/TPP/BBr nanoparticles protected enzymatic liver functionality against ethanol-induced damage. They also prevented histopathological ethanol-induced damage. CONCLUSIONS: Crosslinking CS nanoparticles with HPMCP can mediate controlled drug release in the intestine improving the bioavailability of BBr.

CAR-T cell immunotherapy for ovarian cancer: hushing the silent killer.

As the most lethal gynecologic oncological indication, carcinoma of the ovary has been ranked as the 5th cause of cancer-related mortality in women, with a high percentage of the patients being diagnosed at late stages of the disease and a five-year survival of ~ 30%. Ovarian cancer patients conventionally undergo surgery for tumor removal followed by platinum- or taxane-based chemotherapy; however, a high percentage of patients experience tumor relapse. Cancer immunotherapy has been regarded as a silver lining in the treatment of patients with various immunological or oncological indications; however, mirvetuximab soravtansine (a folate receptor α-specific mAb) and bevacizumab (a VEGF-A-specific mAb) are the only immunotherapeutics approved for the treatment of ovarian cancer patients. Chimeric antigen receptor T-cell (CAR-T) therapy has achieved tremendous clinical success in the treatment of patients with certain B-cell lymphomas and leukemias, as well as multiple myeloma. In the context of solid tumors, CAR-T therapies face serious obstacles that limit their therapeutic benefit. Such hindrances include the immunosuppressive nature of solid tumors, impaired tumor infiltration, lack of qualified tumor-associated antigens, and compromised stimulation and persistence of CAR-Ts following administration. Over the past years, researchers have made arduous attempts to apply CAR-T therapy to ovarian cancer. In this review, we outline the principles of CAR-T therapy and then highlight its limitations in the context of solid tumors. Ultimately, we focus on preclinical and clinical findings achieved in CAR-T-mediated targeting of different ovarian cancer-associated target antigens.

CAR-T cell therapy in triple-negative breast cancer: Hunting the invisible devil.

Triple-negative breast cancer (TNBC) is known as the most intricate and hard-to-treat subtype of breast cancer. TNBC cells do not express the well-known estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expressed by other breast cancer subtypes. This phenomenon leaves no room for novel treatment approaches including endocrine and HER2-specific antibody therapies. To date, surgery, radiotherapy, and systemic chemotherapy remain the principal therapy options for TNBC treatment. However, in numerous cases, these approaches either result in minimal clinical benefit or are nonfunctional, resulting in disease recurrence and poor prognosis. Nowadays, chimeric antigen receptor T cell (CAR-T) therapy is becoming more established as an option for the treatment of various types of hematologic malignancies. CAR-Ts are genetically engineered T lymphocytes that employ the body's immune system mechanisms to selectively recognize cancer cells expressing tumor-associated antigens (TAAs) of interest and efficiently eliminate them. However, despite the clinical triumph of CAR-T therapy in hematologic neoplasms, CAR-T therapy of solid tumors, including TNBC, has been much more challenging. In this review, we will discuss the success of CAR-T therapy in hematological neoplasms and its caveats in solid tumors, and then we summarize the potential CAR-T targetable TAAs in TNBC studied in different investigational stages.