Macrophage cell membrane infused biomimetic liposomes for glioblastoma targeted therapy.

Glioblastoma (GBM) is a highly aggressive malignant brain tumor currently without an effective treatment. Inspired by the recent advances in cell membrane biomimetic nanocarriers and by the key role of macrophages in GBM pathology, we developed macrophage membrane liposomes (MML) for GBM targeting. For the first time, it was assessed the role of macrophage polarization states in the effectiveness of these drug delivery systems. Interestingly, we observed that MML derived from M2 macrophages (M2 MML) presents higher uptake and increased delivery of the anticarcinogenic drug doxorubicin compared to M1 macrophage-derived nanocarriers (M1 MML) and control liposomes (CL). Moreover, the lowest uptake by macrophages of MML reveals promising immune escaping properties. Notably, M2 macrophages unveiled a higher expression of integrin CD49d, a crucial protein involved in the bilateral communication of macrophages with tumor cells. Therefore, our findings suggest the potential of using M2 macrophage membranes to develop novel nanocarriers targeting GBM.

In Vivo Evaluation of the Biocompatibility of Biomaterial Device.

Biomaterials are widely used to produce devices for regenerative medicine. After its implantation, an interaction between the host immune system and the implanted biomaterial occurs, leading to biomaterial-specific cellular and tissue responses. These responses may include inflammatory, wound healing responses, immunological and foreign-body reactions, and even fibrous encapsulation of the implanted biomaterial device. In fact, the cellular and molecular events that regulate the success of the implant and tissue regeneration are played at the interface between the foreign body and the host inflammation, determined by innate and adaptive immune responses. This chapter focuses on host responses that must be taken into consideration in determining the biocompatibility of biomaterial devices when implanted in vivo of animal models.

Study of the immunologic response of marine-derived collagen and gelatin extracts for tissue engineering applications.

The host immunologic response to a specific material is a critical aspect when considering it for clinical implementation. Collagen and gelatin extracted from marine sources have been proposed as biomaterials for tissue engineering applications, but there is a lack of information in the literature about their immunogenicity. In this work, we evaluated the immune response to collagen and/or gelatin from blue shark and codfish, previously extracted and characterized. After endotoxin evaluation, bone marrow-derived macrophages were exposed to the materials and a panel of pro- and anti-inflammatory cytokines were evaluated both for protein quantification and gene expression. Then, the impact of those materials in the host was evaluated through peritoneal injection in C57BL/6 mice. The results suggested shark collagen as the less immunogenic material, inducing low expression of pro-inflammatory cytokines as well as inducible nitric oxide synthase (encoded by Nos2) and high expression of Arginase 1 (encoded by Arg1). Although shark gelatin appeared to be the material with higher pro-inflammatory expression, it also presents a high expression of IL-10 (anti-inflammatory cytokine) and Arginase (both markers for M2-like macrophages). When injected in the peritoneal cavity of mice, our materials demonstrated a transient recruitment of neutrophil, being almost non-existent after 24 hours of injection. Based on these findings, the studied collagenous materials can be considered interesting biomaterial candidates for regenerative medicine as they may induce an activation of the M2-like macrophage population, which is involved in suppressing the inflammatory processes promoting tissue remodeling. STATEMENT OF SIGNIFICANCE: Marine-origin biomaterials are emerging in the biomedical arena, namely the ones based in marine-derived collagen/gelatin proposed as cell templates for tissue regeneration. Nevertheless, although the major cause of implant rejection in clinical practice is the host's negative immune response, there is a lack of information in the literature about the immunological impact of these marine collagenous materials. This work aims to contribute with knowledge about the immunologic response to collagen/gelatin extracted from blue shark and codfish skins. The results demonstrated that despite some differences observed, all the materials can induce a macrophage phenotype related with anti-inflammation resolution and then act as immuno-modulators and anti-inflammatory inducible materials.

Biomimetic and cell-based nanocarriers - New strategies for brain tumor targeting.

In the last two decades no significant advances were achieved in the treatment of the most frequent and malignant types of brain tumors. The main difficulties in achieving progress are related to the incapacity to deliver drugs in therapeutic amounts into the central nervous system and the associated severe side effects. Indeed, to obtain effective treatments, the drugs should be able to cross the intended biological barriers and not being inactivated before reaching the specific therapeutic target. To overcome these challenges the development of synthetic nanocarriers has been widely explored for brain tumor treatment but unfortunately with no clinical translation until date. The use of cell-derived nanocarriers or biomimetic nanocarriers has been studied in the last few years, considering their innate bio-interfacing properties. The ability to carry therapeutic agents and a higher selectivity towards brain tumors would bring new hope for the development of safe and effective treatments. In this review, we explore the biological barriers that need to be crossed for effective delivery in brain tumors, and the types and properties of cell-based nanocarriers (extracellular vesicles and cell-membrane coated nanocarriers) currently under investigation.

The impact of Mesenchymal Stem Cells and their secretome as a treatment for gliomas.

In recent years, we have witnessed a significant increase in the amount of studies using Mesenchymal Stem Cells (MSCs) for cancer therapy, mostly as vectors for drug or gene delivery strategies. This is because of their intrinsic capacity of homing into tumor niches. However, the interactions between MSCs themselves and tumor cells is not fully understood, with contradictory results frequently being observed regarding their effects on cancer cell invasion and proliferation. This poses an important question of safety in respect to the application of these cells. The source of the MSC population used, as well as the type of cancer cells under study might strongly influence this interaction. Moreover, differences in isolation protocols, culture media compositions, time of culture and conditioned media collection, or even timing and mode of MSCs administration to in vivo models of cancer may also affect the interaction MSC-tumor cells. In this review, we drive our focus into malignant brain tumors, particularly gliomas, one of the deadliest forms of cancer. Moreover, we look with some detail into different studies using MSCs as a treatment for brain tumors and compare them, highlighting the main deviations and similarities among them.