Nanoformulations of Plant-Derived Compounds as Emerging Therapeutic Approach for Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) represents one of the most daunting health problems accompanied by progressive undesirable socio-economic effects. Phytochemicals, bioactive ingredients majorly found in plants, have gained momentum for their potential against CRC occurrence and regression. However, these phytoconstituents are not exempt from biopharmaceutical drawbacks; therefore, novel strategies, especially nanotechnology, are exploited to surmount the aforementioned bottlenecks. The current paper aims to comprehensively review the phytochemical-based nanoformulations and their mechanisms in the setting of CRC. METHODS: Electronic databases including Scopus, PubMed, and Web of Science were searched with the keywords "colon cancer" or "colorectal cancer", and "plant", "phytochemical", "extract", or "herb", and "nano", "nanoformulation", "Nanoencapsulation", "nanoparticle", "nanostructure", or "nanoliposome", until January 2021. RESULTS: Of the 1230 research hits, only 69 articles were consequently analyzed. The results indicated nanoformulations of several secondary plant metabolites such as berberine, camptothecin, colchicine, apigenin, chrysin, fisetin, quercetin, curcumin, gallic acid, resveratrol, and ursolic acid have profound effects in a broad range of preclinical models of CRC. A wide variety of nanoformulations have been utilized to deliver these phytochemicals, such as nanocomposite, nanocolloids, and mesoporous silica nanoparticles, which have consequently decreased tumor angiogenesis and mitochondrial membrane potential, increased radical scavenging activity, induced cell cycle arrest at different phases of the cancer cell cycle, and induction of apoptosis process via decreased anti-apoptotic proteins (BRAF, CD44, and Bcl-2) and increased in pro-apoptotic ones (Bax, Fas, caspase 3,8, and 9), as well as modulated biopharmaceutical properties. Chitosan and PEG and their derivatives are among the polymers exploited in the phytochemicals' nanoformulations. CONCLUSION AND PERSPECTIVE: To conclude, nanoformulated forms of natural ingredients depicted outstanding anti-CRC activity that could hold promise for help in treating CRC. However, well-designed clinical trials are needed to build up a whole picture of the health profits of nanoformulation of natural products in CRC management.

An update on dual targeting strategy for cancer treatment.

The key issue in the treatment of solid tumors is the lack of efficient strategies for the targeted delivery and accumulation of therapeutic cargoes in the tumor microenvironment (TME). Targeting approaches are designed for more efficient delivery of therapeutic agents to cancer cells while minimizing drug toxicity to normal cells and off-targeting effects, while maximizing the eradication of cancer cells. The highly complicated interrelationship between the physicochemical properties of nanoparticles, and the physiological and pathological barriers that are required to cross, dictates the need for the success of targeting strategies. Dual targeting is an approach that uses both purely biological strategies and physicochemical responsive smart delivery strategies to increase the accumulation of nanoparticles within the TME and improve targeting efficiency towards cancer cells. In both approaches, either one single ligand is used for targeting a single receptor on different cells, or two different ligands for targeting two different receptors on the same or different cells. Smart delivery strategies are able to respond to triggers that are typical of specific disease sites, such as pH, certain specific enzymes, or redox conditions. These strategies are expected to lead to more precise targeting and better accumulation of nano-therapeutics. This review describes the classification and principles of dual targeting approaches and critically reviews the efficiency of dual targeting strategies, and the rationale behind the choice of ligands. We focus on new approaches for smart drug delivery in which synthetic and/or biological moieties are attached to nanoparticles by TME-specific responsive linkers and advanced camouflaged nanoparticles.

The Application of Hydrogels Based on Natural Polymers for Tissue Engineering.

Hydrogels are known as polymer-based networks with the ability to absorb water and other body fluids. Because of this, the hydrogels are used to preserve drugs, proteins, nutrients or cells. Hydrogels possess great biocompatibility, and properties like soft tissue, and networks full of water, which allows oxygen, nutrients, and metabolites to pass. Therefore, hydrogels are extensively employed as scaffolds in tissue engineering. Specifically, hydrogels made of natural polymers are efficient structures for tissue regeneration, because they mimic natural environment which improves the expression of cellular behavior. Producing natural polymer-based hydrogels from collagen, hyaluronic acid (HA), fibrin, alginate, and chitosan is a significant tactic for tissue engineering because it is useful to recognize the interaction between scaffold with a tissue or cell, their cellular reactions, and potential for tissue regeneration. The present review article is focused on injectable hydrogels scaffolds made of biocompatible natural polymers with particular features, the methods that can be employed to engineer injectable hydrogels and their latest applications in tissue regeneration.

Nanoformulations of natural products for management of metabolic syndrome.

Metabolic syndrome is a common metabolic disorder which has become a public health challenge worldwide. There has been growing interest in medications including natural products as complementary or alternative choices for common chemical therapeutics regarding their limited side effects and ease of access. Nanosizing these compounds may help to increase their solubility, bioavailability, and promisingly enhance their efficacy. This study, for the first time, provides a comprehensive overview of the application of natural-products-based nanoformulations in the management of metabolic syndrome. Different phytochemicals including curcumin, berberine, Capsicum oleoresin, naringenin, emodin, gymnemic acid, resveratrol, quercetin, scutellarin, stevioside, silybin, baicalin, and others have been nanosized hitherto, and their nanosizing method and effect in treatment and alleviating metabolic syndrome have been reviewed and discussed in this study. It has been discovered that there are several pathways or molecular targets relevant to metabolic disorders which are affected by these compounds. Various natural-based nanoformulations have shown promising effect in treatment of metabolic syndrome, and therefore can be considered as future candidates instead of or in conjunction with pharmaceutical drugs if they pass clinical trials successfully.

Correction to: A systematic review of nano formulation of natural products for the treatment of inflammatory bowel disease: drug delivery and pharmacological targets.

The corresponding author, Mohammad Hosein Farzaei, affiliation is Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. The correct spelling of the 7th author surname is Iranpanah.

A systematic review of nano formulation of natural products for the treatment of inflammatory bowel disease: drug delivery and pharmacological targets.

Inflammatory bowel diseases (IBD), which is classified into Crohn's disease and ulcerative colitis, are among chronic gastrointestinal diseases with unknown pathogenesis. Diverse strategies have been applied for the treatment of this chronic disease. However, selective and site-specific routes of drug delivery to the inflamed location of the colon remain of high importance. Consequently, the application and effects of natural products in the form of nanoformulation and stimuli responsive nanoparticles as a novel strategy for the treatment of IBD are discussed in this review article. This approach may potentially overcome some complications that are associated with conventional means of colon drug delivery. Meanwhile, in vitro and in vivo studies pave the way for understanding of the mechanism that lies behind this chronic relapsing disease and potentially more effective treatment. Graphical abstract ᅟ.

Anti-Cancerous Potential of Polyphenol-Loaded Polymeric Nanotherapeutics.

Recent evidence has extensively demonstrated the anticancer potential of nutraceuticals, including plant polyphenols. Polymeric nanocarrier systems have played an important role in improving the physicochemical and pharmacological properties of polyphenols, thus ameliorating their therapeutic effectiveness. This article summarizes the benefits and shortcomings of various polymeric systems developed for the delivery of polyphenols in cancer therapy and reveals some ideas for future work.

Stimulus-responsive liposomes as smart nanoplatforms for drug delivery applications.

Liposomes are known to be promising nanoparticles (NPs) for drug delivery applications. Among different types of self-assembled NPs, liposomes stand out for their non-toxic nature, and their possession of dual hydrophilic-hydrophobic domains. Advantages of liposomes include the ability to solubilize hydrophobic drugs, the ability to incorporate different hydrophilic and lipophilic drugs at the same time, lessening the exposure of host organs to potentially toxic drugs and allowing modification of the surface by a variety of different chemical groups. This modification of the surface, or of the individual constituents, may be used to achieve two important goals. Firstly, ligands for active targeting can be attached that are recognized by cognate receptors over-expressed on the target cells of tissues. Secondly, modification can be used to impart a stimulus-responsive or "smart" character to the liposomes, whereby the cargo is released on demand only when certain internal stimuli (pH, reducing agents, specific enzymes) or external stimuli (light, magnetic field or ultrasound) are present. Here, we review the field of smart liposomes for drug delivery applications.