Exosomes as a Nano-Carrier for Chemotherapeutics: A New Era of Oncology.

Despite the considerable advancements in oncology, cancer remains one of the leading causes of death worldwide. Drug resistance mechanisms acquired by cancer cells and inefficient drug delivery limit the therapeutic efficacy of available chemotherapeutics drugs. However, studies have demonstrated that nano-drug carriers (NDCs) can overcome these limitations. In this sense, exosomes emerge as potential candidates for NDCs. This is because exosomes have better organotropism, homing capacity, cellular uptake, and cargo release ability than synthetic NDCs. In addition, exosomes can serve as NDCs for both hydrophilic and hydrophobic chemotherapeutic drugs. Thus, this review aimed to summarize the latest advances in cell-free therapy, describing how the exosomes can contribute to each step of the carcinogenesis process and discussing how these nanosized vesicles could be explored as nano-drug carriers for chemotherapeutics.

TiO2 Nanoparticles in Cancer Therapy as Nanocarriers in Paclitaxel's Delivery and Nanosensitizers in Phototherapies and/or Sonodynamic Therapy.

Nanomaterials have been offering improvements in different areas due to their unique characteristics, but cytotoxicity associated with their use is still a topic that concerns researchers. Causing cell death, at first glance, may seem to be a problem and the studies regarding signaling pathways involved in this toxicity are still in their infancy. However, there are scenarios in which this feature is desirable, such as in cancer treatment. Anti-cancer therapies aim to eliminate the cells of malignant tumors as selectively as possible. From this perspective, titanium dioxide (TiO2) nanoparticles (NPs) deserve to be highlighted as important and efficient tools. Besides being able to induce cell death, these NPs can also be used to deliver anti-cancer therapeutics. These drugs can originate from natural sources, such as paclitaxel (an antitumoral molecule derived from a vegetal source). The present review aims to explore the recent knowledge of TiO2 NPs as nanocarriers (promoting the nanodelivery of paclitaxel) and as nanosensitizers to be used in phototherapies and/or sonodynamic therapy aiming to treat cancer. Signaling pathways triggered by this nanomaterial inside cells leading to apoptosis (a desirable fate when targeting tumor cells) and challenges related to the clinical translation of these NPs will also receive attention in the future.

Lithium: A Promising Anticancer Agent.

Lithium is a therapeutic cation used to treat bipolar disorders but also has some important features as an anti-cancer agent. In this review, we provide a general overview of lithium, from its transport into cells, to its innovative administration forms, and based on genomic, transcriptomic, and proteomic data. Lithium formulations such as lithium acetoacetate (LiAcAc), lithium chloride (LiCl), lithium citrate (Li3C6H5O7), and lithium carbonate (Li2CO3) induce apoptosis, autophagy, and inhibition of tumor growth and also participate in the regulation of tumor proliferation, tumor invasion, and metastasis and cell cycle arrest. Moreover, lithium is synergistic with standard cancer therapies, enhancing their anti-tumor effects. In addition, lithium has a neuroprotective role in cancer patients, by improving their quality of life. Interestingly, nano-sized lithium enhances its anti-tumor activities and protects vital organs from the damage caused by lipid peroxidation during tumor development. However, these potential therapeutic activities of lithium depend on various factors, such as the nature and aggressiveness of the tumor, the type of lithium salt, and its form of administration and dosage. Since lithium has been used to treat bipolar disorder, the current study provides an overview of its role in medicine and how this has changed. This review also highlights the importance of this repurposed drug, which appears to have therapeutic cancer potential, and underlines its molecular mechanisms.

Exosomes as a nano-carrier for Chemotherapeutics: a new era of oncology

Despite the considerable advancements in oncology, cancer remains one of the leading causes of death worldwide. Drug resistance mechanisms acquired by cancer cells and inefficient drug delivery limit the therapeutic efficacy of available chemotherapeutics drugs. However, studies have demonstrated that nano-drug carriers (NDCs) can overcome these limitations. In this sense, exosomes emerge as potential candidates for NDCs. This is because exosomes have better organotropism, homing capacity, cellular uptake, and cargo release ability than synthetic NDCs. In addition, exosomes can serve as NDCs for both hydrophilic and hydrophobic chemotherapeutic drugs. Thus, this review aimed to summarize the latest advances in cell-free therapy, describing how the exosomes can contribute to each step of the carcinogenesis process and discussing how these nanosized vesicles could be explored as nano-drug carriers for chemotherapeutics.

Trends in Drug Delivery Systems for Natural Bioactive Molecules to Treat Health Disorders: The Importance of Nano-Liposomes.

Drug delivery systems are believed to increase pharmaceutical efficacy and the therapeutic index by protecting and stabilizing bioactive molecules, such as protein and peptides, against body fluids' enzymes and/or unsuitable physicochemical conditions while preserving the surrounding healthy tissues from toxicity. Liposomes are biocompatible and biodegradable and do not cause immunogenicity following intravenous or topical administration. Still, their most important characteristic is the ability to load any drug or complex molecule uncommitted to its hydrophobic or hydrophilic character. Selecting lipid components, ratios and thermo-sensitivity is critical to achieve a suitable nano-liposomal formulation. Nano-liposomal surfaces can be tailored to interact successfully with target cells, avoiding undesirable associations with plasma proteins and enhancing their half-life in the bloodstream. Macropinocytosis-dynamin-independent, cell-membrane-cholesterol-dependent processes, clathrin, and caveolae-independent mechanisms are involved in liposome internalization and trafficking within target cells to deliver the loaded drugs to modulate cell function. A successful translation from animal studies to clinical trials is still an important challenge surrounding the approval of new nano-liposomal drugs that have been the focus of investigations. Precision medicine based on the design of functionalized nano-delivery systems bearing highly specific molecules to drive therapies is a promising strategy to treat degenerative diseases.

Preferential uptake of antibody targeted calcium phosphosilicate nanoparticles by metastatic triple negative breast cancer cells in co-cultures of human metastatic breast cancer cells plus bone osteoblasts.

Calcium phosphosilicate nanoparticles (CPSNPs) are bioresorbable nanoparticles that can be bioconjugated with targeting molecules and encapsulate active agents and deliver them to tumor cells without causing damage to adjacent healthy tissue. Data obtained in this study demonstrated that an anti-CD71 antibody on CPSNPs targets these nanoparticles and enhances their internalization by triple negative breast cancer cells in-vitro. Caspase 3,7 activation, DNA damage, and fluorescent microscopy confirmed the apoptotic breast cancer response caused by targeted anti-CD71-CPSNPs encapsulated with gemcitabine monophosphate, the active metabolite of the chemotherapeutic gemcitabine used to treat cancers including breast and ovarian. Targeted anti-CD71-CPSNPs encapsulated with the fluorophore, Rhodamine WT, were preferentially internalized by breast cancer cells in co-cultures with osteoblasts. While osteoblasts partially internalized anti-CD71-GemMP-CPSNPs, their cell growth was not affected. These results suggest that CPSNPs may be used as imaging tools and selective drug delivery systems for breast cancer that has metastasized to bone.

Lipid-based siRNA Nanodelivery Systems: A Learning Process for Improving Transfer from Concepts to Clinical Applications.

BACKGROUND: The molecular mechanism of silencing genes using small interference RNA is as particular and innovative phenomenon as the proposed delivery systems to release them. Recent advances in RNAi have resulted in the development of multiple siRNA candidates that are currently being evaluated in preclinical / clinical instances. SNALP®, Atuplex® and Rondel® technologies stand out; they are mainly based on polymers, cyclodextrins or lipids. METHOD: The objective of this work is to review the main features that Gene Therapy Medicinal Product under current clinical evaluation present from a pharmaceutical technology point of view; it tries to bring up theoretical concepts that give scientific support to the interpretation of data obtained during pharmaceutical development process. It is basically focused on improving the translation from bench/theoretical concepts to bedside of non viral vectors carrying siRNA. RESULTS: The extensive presence of lipid-based nanoparticle non-viral systems in clinical stages is due to the advantages of their formulations. These include: safety, low immunogenicity, high degree of material properties control, function tuning and ability to impact pharmacokinetics and in vivo biodistribution. This work presents a pharmaceutical approach so as to improve the potential of success in siRNA delivery using liposomal systems. CONCLUSION: Formulation design should be increasingly addressed with industrial criteria; it should be based on quality by design and on the estimation of critical attributes that affect product performance, and supported by a range of characterization techniques and appropriate analytical methods.

Nanoparticle mucoadhesive system as a new tool for fish immune system modulation.

Recently, chitosan-based nanoparticles with mucoadhesive properties emerged as a strategy for mucosal drug release. This study aimed to characterize the interaction of mucoadhesive system chitosancoated PLGA nanoparticles (NPMA) with fish external mucus. NP suspensions with fluorescent probe were prepared and characterized by size, polydispersity, zeta potential and pH measures. In post-exposure fish were observed an increase in fluorescence imaging over time and it was significantly influenced by NPMA concentration. We also observed the main predominance the fluorescence in the spleen, followed by liver, gill and other tissues. The use of mucoadhesive nanocarriers becomes an alternative for administration of drugs and immunomodulators in immersion systems since the nanosystem can adhere to the mucosal surface of the fish with little residual effect in the water.