Folate receptor-mediated delivery system based on chitosan coated polymeric nanoparticles for combination therapy of breast cancer.

Combination therapy using two or more drugs with different mechanisms of action is an effective strategy for treating cancer. This is because of the synergistic effect of complementary drugs that enhances their effectiveness. However, this approach has some limitations, such as non-specific distribution of the drugs in the tumor and the occurrence of dose-dependent toxicity to healthy tissues. To overcome these issues, we have developed a folate receptor-mediated co-delivery system that improves the access of chemotherapy drugs to the tumor site. We prepared a nanoplatform by encapsulating paclitaxel (PTX) and curcumin (CUR) in poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) (PCL-PEG-PCL) co-polymer using a double emulsion method and coating nanoparticles with pH-responsive chitosan-folic acid (CS-FA) conjugate. The nanocarrier's physicochemical properties were studied, confirming successful preparation with appropriate size and morphology. PTX and CUR could be released synchronously in a controlled and acid-facilitated manner. The dual drug-loaded nanocarrier exhibited excellent anti-tumor efficiency in MDA-MB-231 cells in vitro. The active targeting effect of FA concluded from the high inhibitory effect of dual drug-loaded nanocarrier on MDA-MB-231 cells, which have overexpressed folate receptors on their surface, compared to Human umbilical vein endothelial cells (HUVEC). Overall, the nanoengineered folate receptor-mediated co-delivery system provides great potential for safe and effective cancer therapy.

Recent advances and trends in nanoparticles based photothermal and photodynamic therapy.

Light-mediated therapies, including photodynamic therapy (PDT) and photothermal therapy (PTT) have been exploited as minimally invasive techniques for ablation of various tumors., Both modalities may eradicate tumors with minimal side effects to normal tissues and organs. Moreover, developments of light-mediated approaches using nanoparticles (NPs) and photosensitizer (PS) as diagnostic and therapeutic agents may have a crucial role in achieving successful cancer treatment. In recent years, novel nanoplatforms and strategies have been investigated to boost the therapeutic effect.. In this regard, gold, iron oxide, graphene oxide nanoparticles and hybrid nanocomposites have attracted attention.. Moreover, the combination of these materials with PS, in the form of hybrid NPs, reduces in vitro and in vivo normal tissue cytotoxicity, improves their solubility property in the biological environment and enhances the therapeutic effects. In this review, we look into the basic principles of PTT and PDT with their strengths and limitations to treat cancers. We also will discuss light-based nanoparticles and their PTT and PDT applications in the preclinical and clinical translation. Also, recent advances and trends in this field will be discussed along with the clinical challenges of PTT and PDT.

Iron oxide and gold bimetallic radiosensitizers for synchronous tumor chemoradiation therapy in 4T1 breast cancer murine model.

The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research. The present study aims to design a nanoplatform that offers the opportunity to enhance antitumor activity while minimizing side effects. Given the Au-mediated X-ray radiation enhancement and the ability of Fe-based nanomaterials to create reactive oxygen species (ROS) and DNA damage, we anticipated that bimetallic Fe3O4-Au heterodimer would bring strong radiosensitizing capacity. Fe3O4-Au heterodimer surface was covered with bovine serum albumin (BSA) to achieve good surface functionality, stability and prolonged blood circulation. Folic acid (FA) moieties were added to the nanoformulation to increase tumor-homing, specificity and uptake. Finally, curcumin (CUR) was incorporated into the nanoparticle to function as a natural anticancer agent. The integration of all these components has yielded a single nanoplatform, Fe3O4-Au-BSA-FA-CUR, capable of successfully fulfilling the mission of superadditive cancer therapy to avoid the risks of organ removal surgery. The efficacy of the proposed nanoplatform was investigated in vitro and in vivo. High radiosensitizing ability, X-ray-induced ROS generation and DNA damage, and good biocompatibility were demonstrated through in vitro experiments. Also, the administration of Fe3O4-Au-BSA-FA-CUR with X-ray irradiation completely eradicated the tumor without any mortality and toxicity in healthy tissues in vivo. Our results highlight the potential of CUR-loaded Fe3O4-Au-BSA-FA heteronanostructure to enable synergistic localized radiochemotherapy and open up a new door to attractive possibilities that warrant further exploration.

A Lysine-Functionalized Graphene Oxide-Based Nanoplatform for Delivery of Fluorouracil to A549 Human Lung Cancer Cells: A Comparative Study.

Background: Today, increasing attention is being paid to the application of biocompatible polymers as drug carriers with low cytotoxicity in drug delivery systems to enhance the therapeutic effects of anticancer agents. Materials and Methods: In this study, a biocompatible synthetic polymer (grafted on graphene oxide), composed of N-isopropylacrylamide and 1-vinyl-2-pyrrolidone with L-lysine segments (Lys/PNIPAM-PVP/GO), was developed as a nano-vehicle for the drug. This platform was used for the delivery of fluorouracil (FU) to A549 human lung cancer cells. The superior characteristics of the platform included low-cost precursors, easy synthesis, and the presence of many functional groups for loading drugs. To determine and compare the cytotoxic effects of free FU and its formulated form on the A549 cells, MTT assay was performed; the results showed no significant toxicity difference between the two treated groups (free and formulated FU). For further evaluations, cellular uptake assays were performed via fluorescence microscopy and flow cytometry. Results: Both analyses revealed the low internalization of nano-vehicle into the A549 cells, with 4.31% and 8.75% cellular uptakes in the first two and four hours of treatment. Therefore, the low penetration rate reduced the toxicity of drug-loaded nano-vehicle. Conclusion: Finally, DAPI staining and Annexin V-FITC staining were performed as complementary techniques to determine cell apoptosis.

Osteogenic effects of the bioactive small molecules and minerals in the scaffold-based bone tissue engineering.

Reconstruction of the damaged bone is a striking challenge in the medical field. The bone grafts as a current treatment is associated with inherent limitations; hence, the bone tissue engineering as an alternative therapeutic approach has been considered in the recent decades. Bone tissue engineering aims at replacing the lost tissue and restoring its function by recapitulating the natural regeneration process. Concerted participation and combination of the biocompatible materials, osteoprogenitor/ stem cells and bioactive factors closely mimic the bone microenvironment. The bioactive factors regulate the cell behavior and they induce the stem cells to osteogenic differentiation by activating specific signaling cascades. Growth factors (GFs) are the most important bioactive molecules and mediators of the natural bone repair process. Although these soluble factors have approved applications in the bone regeneration, however, there are several limitations such as the instability, high dose requirements, and serious side effects which could restrict their clinical usage. Alternatively, a new generation of bioactive molecules with the osteogenic properties are used. The non-peptide organic or inorganic molecules are physiologically stable and non-immunogenic due to their small size. Many of them are obtained from the natural resources and some are synthesized through the chemical methods. As a result, these molecules have been introduced as the cost-effective osteogenic agents in the bone tissue regeneration. In this paper, three groups of these bioactive agents including the organic small molecules, minerals and metallic nanoparticles have been investigated, considering their function in accelerating the bone regeneration. We review the recent in vitro and in vivo studies that utilized the osteogenic molecules to promote the bone formation in the scaffold-based bone tissue engineering systems.

Lysine-embedded cellulose-based nanosystem for efficient dual-delivery of chemotherapeutics in combination cancer therapy.

Combination therapy by two or multiple drugs with different mechanisms of action is a promising strategy in cancer treatment. In this regard, a wide range of chemotherapeutics has used simultaneously to achieve the synergistic effect and overcome the adverse side effects of single-drug therapy. Herein, we developed a biocompatible nanoparticle-based system composed of nanocrystalline cellulose (NCC) and amino acid l-lysine for efficient co-delivery of model chemotherapeutic methotrexate (MTX) and polyphenol compound curcumin (CUR) to the MCF-7 and MDA-MB-231 cells. The drugs could release in a sustained and acidic-facilitate manner. In vitro cytotoxicity results represented the superior anti-tumor efficacy of the dual-drug-loaded nanocarriers. Possible inhibition of cell growth and induction of apoptosis in the cells treated with different formulations of CUR and MTX were explored by cell cycle analysis and DAPI staining. Overall, the engineered nanosystem can be used as suitable candidates to achieve efficient multi-drug delivery for combination cancer therapy.

Improved synergic therapeutic effects of chemoradiation therapy with the aid of a co-drug-loaded nano-radiosensitizer under conventional-dose X-ray irradiation.

The goal of this work is to harness the advantages of a targeted hybrid nanostructure, BSA-coated Fe3O4 (F)-Au heterodimer, as a radiosensitizer and co-delivery vehicle of chemotherapeutic drugs for enhanced synergic cancer therapy and protection of healthy tissues. F-Au-BSA-MTX-CUR combines the abilities of enhanced X-ray radiation therapy (F-Au), long blood circulation time (BSA), tumor targeting (MTX), enhanced chemotherapy (MTX and CUR), and protection of normal cells against the harmful effects of radiation (CUR). In this work, we present the radioprotective and radiosensitizing effects of CUR on normal tissues and the tumor site, respectively. After technical evaluation, drug loading, drug release behavior, hemolysis assay, transfection efficacy, and cellular uptake studies with fluorescence microscopy, the biosafety and toxicity of the nanostructure was assessed in vitro and in vivo. Also, to confirm its power to improve synergistic chemoradiation therapy in mice, the antitumor effects of the designed treatment plan were assessed in a 4T1-tumor bearing mouse model. The in vivo antitumor effect evaluation interestingly reveals outstanding therapeutic power of the final formulation (F-Au-BSA-MTX-CUR) and further requirement of CUR as a radioprotective. This result importantly revealed the radioprotection effect of CUR. Co-delivery of the chemotherapeutic drugs MTX and CUR, combined with the radiosensitizing effect of the F-Au heterodimer and the radioprotective effect of CUR, showed promising prospects in cancer therapy.

Current developments in green synthesis of metallic nanoparticles using plant extracts: a review.

Metal nanoparticles (MNPs) produced by green approaches have received global attention because of their physicochemical characteristics and their applications in the field of biotechnology. In recent years, the development of synthesizing NPs by plant extracts has become a major focus of researchers because of these NPs have low hazardous effect in the environment and low toxicity for the human body. Synthesized NPs from plants are not only more stable in terms of size and shape, also the yield of this method is higher than the other methods. Moreover, some of these MNPs have shown antimicrobial activity which is consistently confirmed in past few years. Plant extracts have been used as reducing agent and stabilizer of NPs in which we can reduce the toxicity in the environment as well as the human body only by not using chemical agents. Furthermore, the presence of some specific materials in plant extracts could be extremely helpful and effective for the human body; for instance, polyphenol, which may have antioxidant effects has the capability for capturing free radicals before they can react with other biomolecules and cause serious damages. In this article, we focused on of the most common plants which are regularly used to synthesize MNPs along with various methods for synthesizing MNPs from plant extracts.

Theranostic nanoparticles based on magnetic nanoparticles: design, preparation, characterization, and evaluation as novel anticancer drug carrier and MRI contrast agent.

In this work, we reported the synthesis of curcumin (CUR)-loaded hydrophilic and hydrophobic natural amino acids (AAs)-modified iron oxide magnetic nanoparticles (IONPs). Two types of AAs, l-lysine (Lys) and l-phenylalanine (PhA), were selected to study their effects on loading capacity, release profile of CUR, biocompatibility, and anticancer activity. CUR-loaded AAs-modified IONPs (F@AAs@CUR NPs) were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM), and transmission electron microscopy (TEM) techniques. Next, the various kinetic equations were fitted to the release data of CUR from F@Lys@CUR NPs and F@PhA@CUR NPs. Additionally, hemolysis test and MTT assays on HFF-2 and HEK-293 cell lines were performed for determination of biocompatibility of AAs-coated IONPs. Finally, the anticancer activity of F@AAs@CUR NPs examined on MCF-7 breast cancer cell line. The results indicate that these nanocarriers are nontoxic and biocompatible and also F@AAs@CUR NPs are suitable carriers for delivery of curcumin and even other hydrophobic drugs. Also, the MRI training established the effectiveness of IONPs as contrast agent for the revealing of tumor as evidenced from the phantom images as well as higher T2 relaxivity.

Preparation and Characterization of Gold Nanoparticles in the Presence of Citrate and Soybean Seed Extract in an Acidic Conditions.

Through the present study, an eco-friendly method was used to synthesize the gold nanoparticles (GNPs) by using the sodium citrate and extract of the soybean seed as reducing the agents at PH 3. X-Ray diffraction (XRD) method was used to evaluate the crystal structure of as-synthesized NPs and it's revealed that this method leads to well crystallized GNPs. In order to determine the particle size and their distribution, field emission scanning microscopy (FE-SEM) and dynamic light scattering (DLS) were used. The results showed that, the average particle size distribution of synthesized GNPs in solutions containing of the soybean extract and 1% citrate at PH 3 is about 109.6 and 140.9 nm, respectively. Also, we find that the average size of GNPs is 40 and 33 nm from solutions of citrate and soybean extract, respectively. It was concluded that using the extract of soybean seeds as reducing agent can lead to GNPs with small size and narrow size distribution.

Bimetallic nanoparticles: Preparation, properties, and biomedical applications.

Many studies of non-supported bimetallic nanoparticle (BMNP) dispersions, stabilized by ligands or polymers, and copolymers, were started only about 10 years ago. Several preparative procedures have been proposed, and full characterizations on BMNPs have been approved. Studies on BMNPs received huge attention from both scientific and technological communities because most of the NPs' catalytic activity depends on their structural aspects. In this study, we focus on the preparation, properties, and bio-application of BMNPs and introduction of the recent advance in these NPs.