Nanoparticles and cancer therapy: Perspectives for application of nanoparticles in the treatment of cancers

Rapid growth in nanotechnology toward the development of nanomedicine agents holds massive promise to improve therapeutic approaches against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multifunctionality. Nowadays, nanoparticles (NPs) have multiple applications in different branches of science. In recent years, NPs have repetitively been reported to play a significant role in modern medicine. They have been analyzed for different clinical applications, such as drug carriers, gene delivery to tumors, and contrast agents in imaging. A wide range of nanomaterials based on organic, inorganic, lipid, or glycan compounds, as well as on synthetic polymers has been utilized for the development and improvement of new cancer therapeutics. In this study, we discuss the role of NPs in treating cancer among different drug delivery methods for cancer therapy.     

Role of curcumin and its nanoformulations in neurotherapeutics: A comprehensive review

Curcumin, a dietary polyphenol and major constituent of Curcuma longa (Zingiberaceae), is extensively used as a spice in Asian countries. For ages, turmeric has been used in traditional medicine systems to treat various diseases, which was possible because of its anti‐inflammatory, antioxidant, anticancerous, antiepileptic, antidepressant, immunomodulatory, neuroprotective, antiapoptotic, and antiproliferative effects. Curcumin has potent antioxidant, anti‐inflammatory, antiapoptotic, neurotrophic activities, which support its plausible neuroprotective effects in neurodegenerative disease. However, there is limited information available regarding the clinical efficacy of curcumin in neurodegenerative cases. The low oral bioavailability of curcumin may be speculated as a plausible factor that limits its effects in humans. Therefore, utilization of several approaches for the enhancement of bioavailability may improve clinical outcomes. Furthermore, the use of nanotechnology and a targeted drug delivery system may improve the bioavailability of curcumin. The present review is designed to summarize the molecular mechanisms pertaining to the neuroprotective effects of curcumin and its nanoformulations.     

Versatile role of curcumin and its derivatives in lung cancer therapy

Lung cancer is a main cause of death all over the world with a high incidence rate. Metastasis into neighboring and distant tissues as well as resistance of cancer cells to chemotherapy demand novel strategies in lung cancer therapy. Curcumin is a naturally occurring nutraceutical compound derived from Curcuma longa (turmeric) that has great pharmacological effects, such as anti-inflammatory, neuroprotective, and antidiabetic. The excellent antitumor activity of curcumin has led to its extensive application in the treatment of various cancers. In the present review, we describe the antitumor activity of curcumin against lung cancer. Curcumin affects different molecular pathways such as vascular endothelial growth factors, nuclear factor-κB (NF-κB), mammalian target of rapamycin, PI3/Akt, microRNAs, and long noncoding RNAs in treatment of lung cancer. Curcumin also can induce autophagy, apoptosis, and cell cycle arrest to reduce the viability and proliferation of lung cancer cells. Notably, curcumin supplementation sensitizes cancer cells to chemotherapy and enhances chemotherapy-mediated apoptosis. Curcumin can elevate the efficacy of radiotherapy in lung cancer therapy by targeting various signaling pathways, such as epidermal growth factor receptor and NF-κB. Curcumin-loaded nanocarriers enhance the bioavailability, cellular uptake, and antitumor activity of curcumin. The aforementioned effects are comprehensively discussed in the current review to further direct studies for applying curcumin in lung cancer therapy.     

Naphthalocyanine-reconstituted LDL nanoparticles for in vivo cancer imaging and treatment

Low density lipoproteins (LDLs) are naturally occurring nanoparticles that are biocompatible, biodegradable and non-immunogenic. Moreover, the size of LDL particle is precisely controlled (approximately 22 nm) by its apoB-100 component, setting them apart from liposomes and lipid micelles. LDL particles have long been proposed as a nanocarrier for targeted delivery of diagnostics and therapeutics to LDL receptor (LDLR)-positive cancers. Here, we report the design and synthesis of a novel naphthalocyanine (Nc)-based photodynamic therapy (PDT) agent, SiNcBOA, and describe its efficient reconstitution into LDL core (100:1 payload). Possessing a near-infrared (NIR) absorption wavelength (> 800 nm) and extremely high extinction coefficient (> 10(5) M(-1)cm(-1)), SiNcBOA holds the promise of treating deeply seated tumors. Reconstituted LDL particles (r-Nc-LDL) maintain the size and shape of native LDL as determined by transmission electron microscopy, and also retain their LDLR-mediated uptake by cancer cells as demonstrated by confocal microscopy. Its preferential uptake by tumor vs normal tissue was confirmed in vivo by noninvasive optical imaging technique, demonstrating the feasibility of using this nanoparticle for NIR imaging-guided PDT of cancer.     

Retracted: Curcumin derivative L6H4 inhibits proliferation and invasion of gastric cancer cell line BGC-823

Curcumin and its chalcone derivatives have well-known, explicit biological antitumor properties, such as instance antiproliferative and apoptotic effects via multiple molecular targets. In this study, we investigated the anticancer activity of curcumin derivative L6H4 (curcumin L6H4) on gastric cancer cells. Inhibitory effects of curcumin L6H4 on gastric cancer cells (BGC-823) were studied by the diphenyltetrazolium (MTT) assay, and cell apoptosis was detected by Annexin-V/propidium iodide (PI) staining and then analyzed by flow cytometry. A mouse xenotransplant gastric tumor model was established to detect the role of curcumin L6H4 in vivo. The apoptosis-related proteins p53, p21, Bax, and Bcl-2 in BGC-823 cells and mouse xenotransplant models treated with curcumin L6H4 were determined by Western blot analysis. Curcumin L6H4 can significantly inhibit the proliferation and induce the apoptosis of BGC-823 cells, thus enhancing the expression levels of p53, p21, Bax, and Bcl-2 noticeably in vivo and in vitro. Meanwhile, curcumin L6H4 can remarkably suppress the growth of tumor cells in animal models. These results suggest that curcumin derivative L6H4 has potent of antitumor properties in vitro or in vivo.     

Targeting melanoma by small molecules: challenges ahead

Significant progress has been made in targeting melanoma using small molecule inhibitors, but challenges remain. Here we describe the history of screening approaches in melanoma and their limitations. We propose several approaches to refine our screening models to enhance the discovery process. It is hoped that this discussion will stimulate further improvements in our development of small molecules inhibitors for treatment of melanoma patients.     

Therapeutic siRNA: principles, challenges, and strategies

RNA interference (RNAi) is a remarkable endogenous regulatory pathway that can bring about sequence-specific gene silencing. If harnessed effectively, RNAi could result in a potent targeted therapeutic modality with applications ranging from viral diseases to cancer. The major barrier to realizing the full medicinal potential of RNAi is the difficulty of delivering effector molecules, such as small interfering RNAs (siRNAs), in vivo. An effective delivery strategy for siRNAs must address limitations that include poor stability and non-targeted biodistribution, while protecting against the stimulation of an undesirable innate immune response. The design of such a system requires rigorous understanding of all mechanisms involved. This article reviews the mechanistic principles of RNA interference, its potential, the greatest challenges for use in biomedical applications, and some of the work that has been done toward engineering delivery systems that overcome some of the hurdles facing siRNA-based therapeutics.     

Curcumin as an anti-inflammatory agent: Implications to radiotherapy and chemotherapy

Cancer is the second cause of death worldwide. Chemotherapy and radiotherapy are the most common modalities for the treatment of cancer. Experimental studies have shown that inflammation plays a central role in tumor resistance and the incidence of several side effects following both chemotherapy and radiotherapy. Inflammation resulting from radiotherapy and chemotherapy is responsible for adverse events such as dermatitis, mucositis, pneumonitis, fibrosis, and bone marrow toxicity. Chronic inflammation may also lead to the development of second cancer during years after treatment. A number of anti-inflammatory drugs such as nonsteroidal anti-inflammatory agents have been proposed to alleviate chronic inflammatory reactions after radiotherapy or chemotherapy. Curcumin is a well-documented herbal anti-inflammatory agents. Studies have proposed that curcumin can help management of inflammation during and after radiotherapy and chemotherapy. Curcumin targets various inflammatory mediators such as cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor κB (NF-κB), thereby attenuating the release of proinflammatory and profibrotic cytokines, and suppressing chronic production of free radicals, which culminates in the amelioration of tissue toxicity. Through modulation of NF-κB and its downstream signaling cascade, curcumin can also reduce angiogenesis, tumor growth, and metastasis. Low toxicity of curcumin is linked to its cytoprotective effects in normal tissues. This protective action along with the capacity of this phytochemical to sensitize tumor cells to radiotherapy and chemotherapy makes it a potential candidate for use as an adjuvant in cancer therapy. There is also evidence from clinical trials suggesting the potential utility of curcumin for acute inflammatory reactions during radiotherapy such as dermatitis and mucositis.     

Aptamers: Features,Synthesis and Applications

Aptamers have become a topic of interest among the researchers and scientists since they not only possess all of the benefits of antibodies but also possess special qualities including heat stability, low cost, and limitless uses⋅ Here we give a review about the features, applications, and challenges of aptamers and also how they are beneficial over the antibodies for biomedical applications. Their unique features make aptamers a prominent tool in therapeutics, diagnostics, biosensors and targeted drug delivery. In conclusion, aptamers represent exciting materials for a variety of applications and can be modified to improve their properties and to extend their applications in biomedical field.     

姜黄色素及其提制方法

来源于姜科姜黄属植物姜黄根茎的姜黄是国内外食品行业允许使用的重要天然色素之一,具有重要的开发利用价值。姜黄素的主要提取方法可分为有机溶剂提取法和水提取法;精制方法主要包括专一性溶剂法、酸碱法、酶水解法和柱层析法等。文中对各种方法进行了简要介绍和评述。     

Curcumin suppressed the prostate cancer by inhibiting JNK pathways via epigenetic regulation

Curcumin is a component of turmeric and is isolated from the rhizomes of the plant Curcuma longa. Curcumin was reported to have therapeutic effects on prostate cancer. Yet the molecular mechanism of curcumin remains unclear. In this study, mouse prostate cancer xenograft model was established and subjected to curcumin treatment. GST‐c‐Jun pull down kinase assays were performed to study the phospho‐c‐Jun level. Cell Counting Kit‐8 assay kit was utilized to detect the cell viability. Immunoblotting and qRT‐PCR were performed for target gene expression analysis. Curcumin inhibited growth of prostate cancer in vivo as well as promoted apoptosis of LNCaP cells in vitro. Curcumin inhibited JNK pathway and repressed H3K4me3 in LNCaP cells. Combined use of curcumin and JQ‐1 inhibited the prostate cancer efficiently. In conclusion, curcumin inhibits JNK pathway and plays a role in epigenetic regulation of prostate cancer cells by repressing H3K4me3.     

3D Bioprinted cancer models: Revolutionizing personalized cancer therapy

After cardiovascular disease, cancer is the leading cause of death worldwide with devastating health and economic consequences, particularly in developing countries. Inter-patient variations in anti-cancer drug responses further limit the success of therapeutic interventions. Therefore, personalized medicines approach is key for this patient group involving molecular and genetic screening and appropriate stratification of patients to treatment regimen that they will respond to. However, the knowledge related to adequate risk stratification methods identifying patients who will respond to specific anti-cancer agents is still lacking in many cancer types. Recent advancements in three-dimensional (3D) bioprinting technology, have been extensively used to generate representative bioengineered tumor in vitro models, which recapitulate the human tumor tissues and microenvironment for high-throughput drug screening. Bioprinting process involves the precise deposition of multiple layers of different cell types in combination with biomaterials capable of generating 3D bioengineered tissues based on a computer-aided design. Bioprinted cancer models containing patient-derived cancer and stromal cells together with genetic material, extracellular matrix proteins and growth factors, represent a promising approach for personalized cancer therapy screening. Both natural and synthetic biopolymers have been utilized to support the proliferation of cells and biological material within the personalized tumor models/implants. These models can provide a physiologically pertinent cell–cell and cell–matrix interactions by mimicking the 3D heterogeneity of real tumors. Here, we reviewed the potential applications of 3D bioprinted tumor constructs as personalized in vitro models in anticancer drug screening and in the establishment of precision treatment regimens.     

Mesoporous Silica Nanoparticles for Cancer Therapy: Energy-Dependent Cellular Uptake and Delivery of Paclitaxel to Cancer Cells

Biocompatible mesoporous silica nanoparticles, containing the fluorescence dye fluorescein isothiocyanate (FITC), provide a promising system to deliver hydrophobic anticancer drugs to cancer cells. In this study, we investigated the mechanism of uptake of fluorescent mesoporous silica nanoparticles (FMSN) by cancer cells. Incubation with FMSN at different temperatures showed that the uptake was higher at 37°C than at 4°C. Metabolic inhibitors impeded uptake of FMSN into cells. The inhibition of FMSN uptake by nocodazole treatment suggests that microtubule functions are required. We also report utilization of mesoporous silica nanoparticles to deliver a hydrophobic anticancer drug paclitaxel to PANC-1 cancer cells and to induce inhibition of proliferation. Mesoporous silica nanoparticles may provide a valuable vehicle to deliver hydrophobic anticancer drugs to human cancer cells.     

Curcumin inhibits the growth of triple‐negative breast cancer cells by silencing EZH2 and restoring DLC1 expression

Enhancer of zeste homolog 2 (EZH2), an oncogene, is a commonly up‐regulated epigenetic factor in human cancer. Hepatocellular carcinoma deletion gene 1 (DLC1) is an antioncogene that is either expressed at low levels or not expressed in many malignant tumours. Curcumin is a promising anticancer drug that has antitumour effects in many tumours, but its mechanism of action is unclear. Our research demonstrated that EZH2 was up‐regulated in breast cancer (BC) tissues and cells, whereas DLC1 was down‐regulated, and the expression of EZH2 and DLC1 was negatively correlated in BC. By analysing the characteristics of clinical cases, we found that positive expression of EZH2 and negative expression of DLC1 may be predictors of poor prognosis in patients with triple‐negative breast cancer (TNBC). Moreover, knockdown of EZH2 expression restored the expression of DLC1 and inhibited the migration, invasion and proliferation, promoted the apoptosis, and blocked the cell cycle of MDA‐MB‐231 cells. Furthermore, we found that curcumin restored the expression of DLC1 by inhibiting EZH2; it also inhibited the migration, invasion and proliferation of MDA‐MB‐231 cells, promoted their apoptosis and blocked the cell cycle. Finally, xenograft tumour models were used to demonstrate that curcumin restored DLC1 expression by inhibiting EZH2 and also inhibited the growth and promoted the apoptosis of TNBC cells. In conclusion, our results suggest that curcumin can inhibit the migration, invasion and proliferation, promote the apoptosis, block the cycle of TNBC cells and restore the expression of DLC1 by inhibiting the expression of EZH2.     

Targeted drug delivery in pancreatic cancer

Effective drug delivery in pancreatic cancer treatment remains a major challenge. Because of the high resistance to chemo and radiation therapy, the overall survival rate for pancreatic cancer is extremely low. Recent advances in drug delivery systems hold great promise for improving cancer therapy. Using liposomes, nanoparticles, and carbon nanotubes to deliver cancer drugs and other therapeutic agents such as siRNA, suicide gene, oncolytic virus, small molecule inhibitor, and antibody has been a success in recent preclinical trials. However, how to improve the specificity and stability of the delivered drug using ligand or antibody directed delivery represent a major problem. Therefore, developing novel, specific, tumor-targeted drug delivery systems is urgently needed for this terrible disease. This review summarizes the current progress on targeted drug delivery in pancreatic cancer and provides important information on potential therapeutic targets for pancreatic cancer treatment.     

Chitosan-based delivery systems for curcumin: A review of pharmacodynamic and pharmacokinetic aspects

Effective drug delivery is one of the most important issues associated with the administration of therapeutic agents that have low oral bioavailability. Curcumin is an active ingredient in the turmeric plant, which has low oral bioavailability due to its poor aqueous solubility. One strategy that has been considered for enhancing the aqueous solubility, and, thus, its oral bioavailability, is the use of chitosan as a carrier for curcumin. Chitosan is a biodegradable and biocompatible polymer that is relatively water-soluble. Therefore, various studies have sought to improve the aqueous solubility of chitosan. The use of different pharmaceutical excipients and formulation strategies has the potential to improve aqueous solubility, formulation processing, and the overall delivery of hydrophobic drugs. This review focuses on various methods utilized for chitosan-based delivery of curcumin.     

Newly synthesized peptide,Ara-27, exhibits significant improvement in cell-penetrating ability compared to conventional peptides

Cell-penetrating peptides (CPPs) are short amino acid sequences known to act as a vehicle for enhancing the intracellular translocating efficiency of extracellular molecules. Although many groups have attempted to develop peptides with high cell-penetrating efficiencies, very few have demonstrated efficient cellular uptake of CPPs at low concentrations. Here, we describe a newly synthesized peptide derived from Arabidopsis, Ara-27, which exhibits significant improvement in cell-penetrating efficiency compared to existing CPPs. The cell-penetrating efficiency of Ara-27 was compared with the commonly used Tat-protein transduction domain (Tat-PTD) and membrane translocating sequence (MTS) in human dermal fibroblast (HDF) and human dental pulp stem cells (hDPSC). Cell-penetrating efficiency of fluorescein isothiocyanate (FITC)-labeled CPPs were assessed by flow cytometry and visualized by confocal microscopy. Flow cytometric analysis revealed >99% cell-penetrating efficiency for 2 μM Ara-27 in both HDF and hDPSC. In contrast, 2 μM Tat-PTD and MTS showed <10% cell-penetrating efficiency in both cells. In support, relative fluorescence intensities of FITC-labeled Ara-27 were around 8 to 22 times higher than those of Tat-PTD and MTS in both cells. Confocal analysis revealed internalization of 0.2 and 2 μM Ara-27 in both human cells, which was not observed for Tat-PTD and MTS at either concentration. In conclusion, this study describes a novel CPP, Ara-27, which exhibit significant improvement in intracellular uptake compared to conventional CPPs, without affecting cell viability. Thus, development of Ara-27 based peptides may lead to improved delivery of functional cargo such as small molecules, siRNA, and drugs for in vivo studies.