Fabrication of Functional bioMOF-100 Prototype as Drug Delivery System for Breast Cancer Therapy.

Breast cancer is the most frequent cause of cancer death in women, representing the fifth leading cause of cancer death overall. Therefore, the growing search for the development of new treatments for breast cancer has been developed lately as well as drug delivery systems such as biocompatible metal-organic Frameworks (bio-MOFs). These may be promising and attractive for drug incorporation and release. The present study aims to develop a drug carrier system RCA (bioMOF-100 submitted to the activation process) containing incorporated curcumin (CCM), whose material surface is coated with folic acid molecules (FA) to promote the targeting of drug carrier systems to the tumor region. They were synthesized and characterized using several characterization techniques. The materials were submitted to drug encapsulation tests, whose encapsulation efficiency was 32.80% for CCM@RCA-1D. Using the 1H nuclear magnetic resonance (NMR) spectroscopy technique, it was possible to verify the appearance of signals referring to folic acid, suggesting success in the functionalization of these matrices. In vitro tests such as cell viability and type of cell death were evaluated in both series of compounds (CCM@RCA-1D, CCM@RCA-1D/FA) in breast tumor lines. The results revealed low toxicity of the materials and cell death by late apoptosis. Thus, these results indicate that the matrices studied can be promising carriers in the treatment of breast cancer.

Metal-organic frameworks for diagnosis and therapy of infectious diseases.

Infectious diseases are one of the leading cause of mortality and morbidity worldwide. Metal-Organic Frameworks (MOFs), which are porous coordination materials composed of bridging organic ligands and metallic ions or clusters, exhibits great potential to be used against several pathogens, such as bacteria, viruses, fungi and protozoa. MOFs can show sustained release capability, high surface area, adjustable pore size and structural flexibility, which makes them good candidates for new therapeutic systems. This review provides a detailed summary of the biological application of MOFs, focussing on diagnosis and treatment of infectious diseases. MOFs have been reported for usage as antimicrobial agents, drug delivery systems, therapeutic composites, nanozymes and phototherapies. Furthermore, different MOF-based biosensors have also been developed to detect specific pathogens by electrochemical, fluorometric and colorimetric assays. Finally, we present limitations and perspectives in this field.

Highlights Regarding the Use of Metallic Nanoparticles against Pathogens Considered a Priority by the World Health Organization.

The indiscriminate use of antibiotics has facilitated the growing resistance of bacteria, and this has become a serious public health problem worldwide. Several microorganisms are still resistant to multiple antibiotics and are particularly dangerous in the hospital and nursing home environment, and to patients whose care requires devices, such as ventilators and intravenous catheters. A list of twelve pathogenic genera, which especially included bacteria that were not affected by different antibiotics, was released by the World Health Organization (WHO) in 2017, and the research and development of new antibiotics against these genera has been considered a priority. The nanotechnology is a tool that offers an effective platform for altering the physicalchemical properties of different materials, thereby enabling the development of several biomedical applications. Owing to their large surface area and high reactivity, metallic particles on the nanometric scale have remarkable physical, chemical, and biological properties. Nanoparticles with sizes between 1 and 100 nm have several applications, mainly as new antimicrobial agents for the control of microorganisms. In the present review, more than 200 reports of various metallic nanoparticles, especially those containing copper, gold, platinum, silver, titanium, and zinc were analyzed with regard to their anti-bacterial activity. However, of these 200 studies, only 42 reported about trials conducted against the resistant bacteria considered a priority by the WHO. All studies are in the initial stage, and none are in the clinical phase of research.

Stimuli-responsive Drug Delivery Nanocarriers in the Treatment of Breast Cancer.

Stimuli-responsive drug-delivery nanocarriers (DDNs) have been increasingly reported in the literature as an alternative for breast cancer therapy. Stimuli-responsive DDNs are developed with materials that present a drastic change in response to intrinsic/chemical stimuli (pH, redox and enzyme) and extrinsic/physical stimuli (ultrasound, Near-infrared (NIR) light, magnetic field and electric current). In addition, they can be developed using different strategies, such as functionalization with signaling molecules, leading to several advantages, such as (a) improved pharmaceutical properties of liposoluble drugs, (b) selectivity with the tumor tissue decreasing systemic toxic effects, (c) controlled release upon different stimuli, which are all fundamental to improving the therapeutic effectiveness of breast cancer treatment. Therefore, this review summarizes the use of stimuli-responsive DDNs in the treatment of breast cancer. We have divided the discussions into intrinsic and extrinsic stimuli and have separately detailed them regarding their definitions and applications. Finally, we aim to address the ability of these stimuli-responsive DDNs to control the drug release in vitro and the influence on breast cancer therapy, evaluated in vivo in breast cancer models.

Recent Advances in the Use of Metallic Nanoparticles with Antitumoral Action - Review.

The term cancer represents a set of more than 100 diseases that are caused due to an uncontrolled growth of cells; and their subsequent spread to the other tissues and organs of the body by a phenomenon, called 'metastasis'. According to the estimates provided by the World Health Organization (WHO), cancer is expected to account for about 10 million deaths per year by 2020 and 21 million cancer cases, which may lead to 13 million deaths by 2030, making cancer as the cause of highest mortality in contrast to other diseases. The search for potential therapeutics against cancer, which can reduce the side-effects that occur due to the difficulty of recognition between cancerous and normal cells, has ever been increased. In this view, nanotechnology, especially metallic nanoparticles (MNPs), comes to aid in the development of novel therapeutic agents, which may be synthesized or modified with the most diverse functional chemical groups; this property makes the metallic nanoparticles suitable for conjugation with already known drugs or prospective drug candidates. The biocompatibility, relatively simple synthesis, size flexibility and easy chemical modification of its surface, all make the metallic nanoparticles highly advantageous for opportune diagnosis and therapy of cancer. The present article analyzes and reports the anti-tumor activities of 78 papers of various metallic nanoparticles, particularly the ones containing copper, gold, iron, silver and titanium in their composition.

Characteristics, Properties and Analytical Methods of Paclitaxel: A Review.

Paclitaxel is a diterpenoid pseudoalkaloid, isolated from Taxus brevifolia, and is largely used as an antitumoral drug. The formulation of paclitaxel known as Taxol® employs a mixture of Cremophor EL and dehydrated ethanol, due the low drug water solubility. However, Taxol® causes some unwanted side effects due to the presence of Cremophor EL and ethanol in the formulation. Based on this, there is a need for the development of drug delivery systems to enhance the solubility, permeability and stability of paclitaxel and to promote a controlled and targeted delivery for better therapeutic effect and reduced side effects. In addition, the drug has been qualitatively and quantitatively analyzed in different delivery systems. In this context, several approaches were reported focusing on the optimization of analytical methods and development of new ones, considering the need of a fast, simple, with enough sensibility and selectivity assay, which can be a problem in some analysis. This review presents a summary of methods used in quantification of paclitaxel in different matrices, such as plasma, urine, plant extract, cells and delivery systems.

Synthesis of whey peptide-iron complexes: Influence of using different iron precursor compounds.

Iron-binding peptides are an alternative for increasing the bioavailability of iron and to decreasing its pro-oxidant effect. This study aimed to synthesize and characterize peptide-iron complexes using FeCl2 or FeSO4 as the iron precursor compounds. Whey protein isolate (WPI), WPI hydrolyzed with pancreatin, and its fractions obtained via ultrafiltration (cut-off 5kDa) were used as ligands. The fluorescence intensity of the ligands significantly decreased as the iron concentration increased as a result of metal coordination with the iron-binding sites, which may have led to changes in the microenvironment of tryptophan. For both iron precursor compounds, the primary iron-binding site was carboxylate groups, and the linkage occurred via a bidentate coordination mode with two vibrational modes assigned to the COOFe linkage. However, infrared spectroscopy and thermal analysis results showed that the dynamics of the interaction is different for the iron precursor. The iron source may be of great importance because it may impact iron absorption and the pro-oxidant effect of the mineral.