Corrigendum: Mesenchymal stromal cell derived extracellular vesicles as a therapeutic tool: immune regulation, MSC priming, and applications to SLE.

[This corrects the article DOI: 10.3389/fimmu.2024.1355845.].

Mesenchymal stromal cell derived extracellular vesicles as a therapeutic tool: immune regulation, MSC priming, and applications to SLE.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a dysfunction of the immune system. Mesenchymal stromal cell (MSCs) derived extracellular vesicles (EVs) are nanometer-sized particles carrying a diverse range of bioactive molecules, such as proteins, miRNAs, and lipids. Despite the methodological disparities, recent works on MSC-EVs have highlighted their broad immunosuppressive effect, thus driving forwards the potential of MSC-EVs in the treatment of chronic diseases. Nonetheless, their mechanism of action is still unclear, and better understanding is needed for clinical application. Therefore, we describe in this review the diverse range of bioactive molecules mediating their immunomodulatory effect, the techniques and possibilities for enhancing their immune activity, and finally the potential application to SLE.

International Society for Extracellular Vesicles Workshop. QuantitatEVs: multiscale analyses, from bulk to single extracellular vesicle.

The 'QuantitatEVs: multiscale analyses, from bulk to single vesicle' workshop aimed to discuss quantitative strategies and harmonized wet and computational approaches toward the comprehensive analysis of extracellular vesicles (EVs) from bulk to single vesicle analyses with a special focus on emerging technologies. The workshop covered the key issues in the quantitative analysis of different EV-associated molecular components and EV biophysical features, which are considered the core of EV-associated biomarker discovery and validation for their clinical translation. The in-person-only workshop was held in Trento, Italy, from January 31st to February 2nd, 2023, and continued in Milan on February 3rd with "Next Generation EVs", a satellite event dedicated to early career researchers (ECR). This report summarizes the main topics and outcomes of the workshop.

Surface Modification of Lipid-Based Nanoparticles.

There is a growing interest in the development of lipid-based nanocarriers for multiple purposes, including the recent increase of these nanocarriers as vaccine components during the COVID-19 pandemic. The number of studies that involve the surface modification of nanocarriers to improve their performance (increase the delivery of a therapeutic to its target site with less off-site accumulation) is enormous. The present review aims to provide an overview of various methods associated with lipid nanoparticle grafting, including techniques used to separate grafted nanoparticles from unbound ligands or to characterize grafted nanoparticles. We also provide a critical perspective on the usefulness and true impact of these modifications on overcoming different biological barriers, with our prediction on what to expect in the near future in this field.

Colorectal cancer inhibition by BET inhibitor JQ1 is MYC-independent and not improved by nanoencapsulation.

Bromodomain and extraterminal domain protein inhibitors (BETi) for cancer treatment did not convince during their first clinical trials. Their epigenetic mechanism of action is still not well understood, even if MYC is generally considered as its main downstream target. In this context, we intended to assess two new nanoformulations of the BETi JQ1 for the treatment of colorectal cancer (CRC). JQ1 was encapsulated at 10 mg/mL in lipid nanocapsules (LNC) or polymeric micelles (PM), both compatible for an intravenous administration. Their effect was compared with free JQ1 on several CRC cell lines in vitro and with daily intraperitoneal cyclodextrin (CD)-loaded JQ1 on the CT26 CRC tumor model in vivo. We showed that LNC preferentially accumulated in tumor, liver, and lymph nodes. LNC-JQ1 and CD-JQ1 similarly delayed tumor growth and increased median survival from 15 to 23 or 20.5 days. JQ1 altered MYC in only two among four CRC cell lines. This MYC-independence found in CT26 was confirmed in vivo by PCR and immunohistochemistry. The main explanation of the JQ1 anticancer effect was an increase in apoptosis. The investigation of its impact on the tumor microenvironment did not show significant effects. Finally, JQ1 association with irinotecan did not synergize in vivo with JQ1 nanoformulations. In conclusion, we demonstrated that the JQ1 anticancer effect was not improved by nanoencapsulation even if their tumor delivery was probably higher. MYC inhibition was not associated to JQ1 efficacy in the case of the CT26 CRC murine model.

Inhibition of colorectal cancer-associated fibroblasts by lipid nanocapsules loaded with acriflavine or paclitaxel.

Crosstalk between cancer-associated fibroblasts (CAFs) and colorectal cancer cells promotes tumor growth and contributes to chemoresistance. In this study, we assessed the sensitivity of a primary CAF cell line, CT5.3hTERT, to standard-of-care and alternative cytotoxic treatments. Paclitaxel (PTX) and acriflavine (ACF) were identified as the most promising molecules to inhibit CAF development. To allow the translational use of both drugs, we developed lipid nanocapsule (LNC) formulations for PTX and ACF. Finally, we mixed CAFs and tumor cell lines in a cocultured spheroid, and the effect of both drugs was investigated by histological analyses. We demonstrated CAF inhibition by LNC-ACF and whole tumor inhibition by LNC-PTX. Altogether, we proposed a new strategy to reduce CAF populations in the colorectal microenvironment that should be tested in vivo.

Nanotechnology is an important strategy for combinational innovative chemo-immunotherapies against colorectal cancer.

Colorectal cancer (CRC) is among the five most commonly diagnosed cancers worldwide, constituting 6% of all cancers and the third leading cause of cancer death. CRC is the third and second most frequent cancer in men and women worldwide, accounting for 14% and 13% of all cancer incidence rates, respectively. CRC incidence is decreasing in older populations, but it has been significantly rising worldwide in adolescents and adults younger than 50 years old. Significant advances in the screening methods and surgical procedures have been underlying the reduction of the CRC incidence rate in older populations. However, there is an urgent demand for the development of alternative effective therapeutic options to overcome advanced metastatic CRC, while preventing disease recurrence. This review addresses the immune and CRC biology, summarizing the recent advances on the immune and/or therapeutic regimens currently in clinical use. We will focus on the emerging role of nanotechnology in the development of combinational therapies targeting and thereby regulating the function of the major players in CRC progression and immune evasion.

Temozolomide-loaded photopolymerizable PEG-DMA-based hydrogel for the treatment of glioblastoma.

Glioblastoma is the most frequent primary malignant brain tumor in adults. Despite treatments including surgery, radiotherapy and chemotherapy by oral Temozolomide (TMZ), the prognosis of patients with glioblastoma remains very poor. We hypothesized that a polyethylene glycol dimethacrylate (PEG-DMA) injectable hydrogel would provide a sustained and local delivery of TMZ. The hydrogel photopolymerized rapidly (<2min) and presented a viscous modulus (≈10kPa). TMZ release kinetic presented two phases: a linear burst release of 45% of TMZ during the first 24h, followed by a logarithmic release of 20% over the first week. The in vivo tolerability study showed that the unloaded hydrogel did not induce apoptosis in mice brains nor increased microglial activation. In vivo, the anti-tumor efficacy of TMZ-hydrogel was evaluated on xenograft U87MG tumor-bearing nude mice. The tumor weight of mice treated with the photopolymerized TMZ hydrogel drastically decreased compared with all other groups. Higher apoptosis (located at the center of the tumor) was also observed. The present study demonstrates the potential of a photopolymerizable TMZ-loaded hydrogel to treat glioblastoma.