Actuation-Mediated Compression of a Mechanoresponsive Hydrogel by Soft Robotics to Control Release of Therapeutic Proteins.

Therapeutic proteins, the fastest growing class of pharmaceuticals, are subject to rapid proteolytic degradation in vivo, rendering them inactive. Sophisticated drug delivery systems that maintain protein stability, prolong therapeutic effects, and reduce administration frequency are urgently required. Herein, a mechanoresponsive hydrogel is developed contained within a soft robotic drug delivery (SRDD) device.

Potential of Natural Phenolic Compounds against Doxorubicin-Induced Chemobrain: Biological and Molecular Mechanisms Involved.

Chemotherapy-induced cognitive impairment or "chemobrain" is a prevalent long-term complication of chemotherapy and one of the more devastating. Most of the studies performed so far to identify the cognitive dysfunctions induced by antineoplastic chemotherapies have been focused on treatment with anthracyclines, frequently administered to breast cancer patients, a population that, after treatment, shows a high possibility of long survival and, consequently, of chemobrain development. In the last few years, different possible strategies have been explored to prevent or reduce chemobrain induced by the anthracycline doxorubicin (DOX), known to promote oxidative stress and inflammation, which have been strongly implicated in the development of this brain dysfunction.

Hyaluronic Acid-Mediated Phenolic Compound Nanodelivery for Cancer Therapy.

Phenolic compounds are bioactive phytochemicals showing a wide range of pharmacological activities, including anti-inflammatory, antioxidant, immunomodulatory, and anticancer effects. Moreover, they are associated with fewer side effects compared to most currently used antitumor drugs. Combinations of phenolic compounds with commonly used drugs have been largely studied as an approach aimed at enhancing the efficacy of anticancer drugs and reducing their deleterious systemic effects.

Nutraceutical-Based Nanoformulations for Breast and Ovarian Cancer Treatment.

Different strategies have been investigated for a more satisfactory treatment of advanced breast cancer, including the adjuvant use of omega-3 polyunsaturated fatty acids (PUFAs). These nutritional compounds have been shown to possess potent anti-inflammatory and antiangiogenic activities, the capacity to affect transduction pathways/receptors involved in cell growth and to reprogram tumor microenvironment. Omega-3 PUFA-containing nanoformulations designed for drug delivery in breast cancer were shown to potentiate the effects of enclosed drugs, enhance drug delivery to target sites, and minimize drug-induced side effects.

Preparation and Study of Solid Lipid Nanoparticles Based on Curcumin, Resveratrol and Capsaicin Containing Linolenic Acid.

Linolenic acid (LNA) is the most highly consumed polyunsaturated fatty acid found in the human diet. It possesses anti-inflammatory effects and the ability to reverse skin-related disorders related to its deficiency. The purpose of this work was to encapsulate LNA in solid lipid nanoparticles (SLNs) based on curcumin, resveratrol and capsaicin for the treatment of atopic dermatitis.

New Insights on the Effects of Dietary Omega-3 Fatty Acids on Impaired Skin Healing in Diabetes and Chronic Venous Leg Ulcers.

Long-chain Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) are widely recognized as powerful negative regulators of acute inflammation. However, the precise role exerted by these dietary compounds during the healing process is still largely unknown, and there is increasing interest in understanding their specific effects on the implicated cells/molecular factors. Particular attention is being focused also on their potential clinical application in chronic pathologies characterized by delayed and impaired healing, such as diabetes and vascular diseases in lower limbs.

Characterization of a hyaluronic acid and folic acid-based hydrogel for cisplatin delivery: Antineoplastic effect in human ovarian cancer cells in vitro.

We successfully prepared and characterized a hyaluronic acid- and folic acid-based hydrogel for the delivery of cisplatin (GEL-CIS) with the aim to induce specific and efficient incorporation of CIS into ovarian cancer (OC) cells, improve its antineoplastic effect and avoid CIS-resistance. The slow and controlled release of the drug from the polymeric network and its swelling degree at physiologic pH suggested its suitability for CIS delivery in OC. We compared here the effects of pure CIS to that of GEL-CIS on human OC cell lines, either wild type or CIS-resistant, in basal conditions and in the presence of macrophage-derived conditioned medium, mimicking the action of tumor-associated macrophages in vivo.

Recent Advances in Nanotechnology for the Treatment of Melanoma.

Melanoma is one of the most aggressive forms of skin cancer, with few possibilities for therapeutic approaches, due to its multi-drug resistance and, consequently, low survival rate for patients. Conventional therapies for treatment melanoma include radiotherapy, chemotherapy, targeted therapy, and immunotherapy, which have various side effects. For this reason, in recent years, pharmaceutical and biomedical research has focused on new sito-specific alternative therapeutic strategies.

The Combination of Sulforaphane and Fernblock XP Improves Individual Beneficial Effects in Normal and Neoplastic Human Skin Cell Lines.

Plenty of evidence supports the health effects exerted by dietary supplements containing phytochemicals, but the actual efficacy and safety of their combinations have been seldom experimentally evaluated. On this basis, we investigated in vitro the antioxidant/antineoplastic efficacy and anti-aging activity of a dietary supplement containing sulforaphane (SFN), a sulfur-isothiocyanate present in broccoli, combined with the patented extract Fernblock XP (FB), obtained from the tropical fern . We evaluated the effect of SFN and FB, alone or in combination, on migration ability, matrix metalloproteinases (MMP) production, neoangiogenic potential and inflammasome activation in human WM115 and WM266-4 melanoma cells.

Omega-3 PUFA Responders and Non-Responders and the Prevention of Lipid Dysmetabolism and Related Diseases.

The long-chain omega-3 polyunsaturated fatty acids (LC-omega-3 PUFAs) eicosapentaenoic acid and docosahexaenoic acid are the most popular dietary supplements recommended for the prevention/management of lipid dysmetabolisms and related diseases. However, remarkable inconsistencies exist among the outcomes of the human intervention studies in this field, which contrast with the impressive homogeneity of positive results of most of the preclinical studies. In the present review, we will firstly examine a series of factors-such as background diet composition, gut microbiota and genetic/epigenetic variants, which may lie beneath these inconsistencies.

Anti-Irritant and Anti-Inflammatory Effects of DHA Encapsulated in Resveratrol-Based Solid Lipid Nanoparticles in Human Keratinocytes.

We recently found that the dietary long chain omega-3 polyunsaturated fatty acid (LC-ω-3 PUFA), docosahexaenoic acid (DHA), showed enhanced antineoplastic activity against colon cancer cells if encapsulated in resveratrol-based solid lipid nanoparticles (RV-SLNs). In the present study, we investigated whether the DHA enclosed in RV-SLNs (DHA-RV-SLNs) could have the potential of attenuating irritation and inflammation caused by environmental factors at the skin level. To this aim, we used two keratinocyte lines (HaCaT and NCTC 2544 cells) and exposed them to the cytotoxic action of the surfactant, sodium dodecyl sulfate (SDS), as an in vitro model of irritation, or to the pro-inflammatory activity of the cytokine TNF-α.

Nanomedicine-based formulations containing ω-3 polyunsaturated fatty acids: potential application in cardiovascular and neoplastic diseases.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are dietary factors involved in the prevention of cardiovascular, inflammatory, and neoplastic diseases. A multidisciplinary approach - based on recent findings in nutritional science, lipid biochemistry, biotechnology, and biology of inflammation and cancer - has been recently employed to develop ω-3 PUFA-containing nanoformulations with an aim to protect these fatty acids from degradation, increase their bioavailability and delivery to target tissues, and, thus, enhance their bioactivity. In some cases, these nanoformulations were designed to administer ω-3 PUFAs in combination with other nutraceuticals or conventional/innovative drugs.

Xanthan gum-based materials for omega-3 PUFA delivery: Preparation, characterization and antineoplastic activity evaluation.

Xanthan gum-based microspheres and hydrogels, useful for targeted colorectal release of omega-3 polyunsaturated fatty acids (PUFAs), were successfully prepared and characterized. In particular, the microsphere size, as well as the high hydrogel swelling degree at pH 7.4, and the omega-3 PUFA loading efficiency of both the materials suggested their suitability for colorectal delivery.

Combination of ω-3 fatty acids and cisplatin as a potential alternative strategy for personalized therapy of metastatic melanoma: an in-vitro study.

The recently developed therapeutic strategies have led to unprecedented improvements in the control of metastatic melanoma and in the survival of specific subgroups of patients. However, drug resistance, low response rates, and undesired side effects make these treatments not suitable or tolerable for all the patients, and chemotherapeutic treatments appear still indispensable, at least for subgroups of patients. New combinatory strategies are also under investigation as tailored treatments or salvage therapies, including combined treatments of immunotherapy with conventional chemotherapy.

Omega-3 PUFA Loaded in Resveratrol-Based Solid Lipid Nanoparticles: Physicochemical Properties and Antineoplastic Activities in Human Colorectal Cancer Cells In Vitro.

New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC), one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the antineoplastic therapies with either conventional or single-targeted drugs could take advantage from a combined treatment with omega-3 polyunsaturated fatty acids (omega-3 PUFA). These nutrients, shown to be safe at the dosage generally used in human trials, are able to modulate molecules involved in colon cancer cell growth and survival.

Long-chain omega-3 fatty acids and cancer: any cause for concern?

Purpose Of Review: Recently, concerns have been raised with regard to the recommended doses of marine long-chain omega-3 polyunsaturated fatty acids (LC-omega-3 PUFAs) especially in relation to cancer risk and treatment. There is urgent need to clarify this point. This review considers the most recent evidence related to the potential risk of developing cancer with high LC-omega-3 PUFA intakes, and possible research strategies to better elucidate this matter.

Protective Effects of ω-3 PUFA in Anthracycline-Induced Cardiotoxicity: A Critical Review.

It has been demonstrated that ω-3 polyunsaturated fatty acids (ω-3 PUFA) may exert a beneficial role as adjuvants in the prevention and treatment of many disorders, including cardiovascular diseases and cancer. Particularly, several in vitro and in vivo preclinical studies have shown the antitumor activity of ω-3 PUFA in different kinds of cancers, and several human studies have shown that ω-3 PUFA are able to decrease the risk of a series of cardiovascular diseases. Several mechanisms have been proposed to explain their pleiotropic beneficial effects.

Modulation of Ras/ERK and Phosphoinositide Signaling by Long-Chain n-3 PUFA in Breast Cancer and Their Potential Complementary Role in Combination with Targeted Drugs.

A potential complementary role of the dietary long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFA) in combination with innovative mono-targeted therapies has recently been proposed. These compounds are thought to act pleiotropically to prevent the development and progression of a variety of cancers, including breast cancer. We hereinafter critically analyze the reports investigating the ability of LCn-3 PUFA to modulate the Ras/ERK and the phosphoinositide survival signaling pathways often aberrantly activated in breast cancer and representing the main targets of innovative therapies.

Role of β-catenin signaling in the anti-invasive effect of the omega-3 fatty acid DHA in human melanoma cells.

Background: We previously found that docosahexaenoic acid (DHA), a dietary polyunsaturated fatty acid present at high level in fatty fish, inhibited cell growth and induced differentiation of melanoma cells in vitro by increasing nuclear β-catenin content. An anti-neoplastic role of nuclear β-catenin was suggested in melanoma, and related to the presence in the melanocyte lineage of the microphtalmia transcription factor (MITF), which interferes with the transcription of β-catenin/TCF/LEF pro-invasive target genes.

Objective: In the present work we investigated if DHA could inhibit the invasive potential of melanoma cells, and if this effect could be related to DHA-induced alterations of the Wnt/β-catenin signaling, including changes in MITF expression.

How plausible is the use of dietary n-3 PUFA in the adjuvant therapy of cancer?

Considerable debate exists regarding the potential antineoplastic effect of dietary long-chain n-3 PUFA contained in fatty fishes. Since the majority of published data has proven that their intake does not induce toxic or carcinogenic effects in humans, their possible preventive use against cancer has been suggested. On the other hand, it is unlikely that they could be effective in cancer patients as a single therapy.

Epigenetic regulation of gene expression and M2 macrophage polarization as new potential omega-3 polyunsaturated fatty acid targets in colon inflammation and cancer.

Introduction: It has become increasingly clear that dietary habits may affect the risk/progression of chronic diseases with a pathogenic inflammatory component, such as colorectal cancer. Considerable attention has been directed toward the ability of nutritional agents to target key molecular pathways involved in these inflammatory-related diseases.

Areas Covered: ω-3 Polyunsaturated fatty acids (PUFA) and their oxidative metabolites have attracted considerable interest as possible anti-inflammatory and anti-cancer agents, especially in areas such as the large bowel, where the influence of orally introduced substances is high and tumors show deranged PUFA patterns.

Reduction of Oxidative/Nitrosative Stress in Brain and its Involvement in the Neuroprotective Effect of n-3 PUFA in Alzheimer's Disease.

Plenty of evidence has shown that an enhanced oxidative or nitrosative stress may play a central role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). The suppressive effect of n-3 polyunsaturated fatty acids (n-3 PUFA) against oxidative/nitrosative stressinduced injury in nervous tissues has recently received increasing interest. A number of human experimental studies have concurred to demonstrate that they may exert a substantial preventive role, especially in the very early phase of mild cognitive impairment (MCI) preceding AD.

Omega-3 Polyunsaturated Fatty Acids: The Way Forward in Times of Mixed Evidence.

Almost forty years ago, it was first hypothesized that an increased dietary intake of omega-3 polyunsaturated fatty acids (PUFA) from fish fat could exert protective effects against several pathologies. Decades of intense preclinical investigation have supported this hypothesis in a variety of model systems. Several clinical cardiovascular studies demonstrated the beneficial health effects of omega-3 PUFA, leading medical institutions worldwide to publish recommendations for their increased intake.

Long-chain n-3 PUFA against breast and prostate cancer: Which are the appropriate doses for intervention studies in animals and humans?

The potential antineoplastic effect of the long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) remains a highly controversial issue. Numerous animal studies have supported the anticancer role of these dietary fatty acids, whereas conflicting results have been obtained in population studies, and only a few intervention human trials have been so far performed. In view of the possibility that the anticancer effects may be maximally observed within a defined range of EPA and DHA doses, herein we critically review the results and doses used in both animal studies and human clinical trials focusing on the possible n-3 PUFA protective effects against breast and prostate cancer.

Antioxidant and anti-inflammatory effects of selected natural compounds contained in a dietary supplement on two human immortalized keratinocyte lines.

Several advantages may derive from the use of dietary supplements containing multiple natural antioxidants and/or anti-inflammatory agents. At present, however, there is scarce information on the properties and potential of combined supplements. To fill the gap, the antioxidant and anti-inflammatory activities exerted by a combination of seven natural components (coenzyme Q10, krill oil, lipoic acid, resveratrol, grape seed oil, α-tocopherol, and selenium) contained in a dietary supplement used for the prevention of skin disorders were investigated in vitro.