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Targeting Tumor Immunosuppressive Microenvironment for the Prevention of Hepatic Cancer: Applications of Traditional Chinese Medicines in Targeted Delivery.
Zhang, LY, Zhang, JG, Yang, X, Cai, MH, Zhang, CW, Hu, ZM
Current topics in medicinal chemistry. 2020;(30):2789-2800
Abstract
Traditional Chinese Medicine (TCM) is one of the ancient and most accepted alternative medicinal systems in the world for the treatment of health ailments. World Health Organization recognizes TCM as one of the primary healthcare practices followed across the globe. TCM utilizes a holistic approach for the diagnosis and treatment of cancers. The tumor microenvironment (TME) surrounds cancer cells and plays pivotal roles in tumor development, growth, progression, and therapy resistance. TME is a hypoxic and acidic environment that includes immune cells, pericytes, fibroblasts, endothelial cells, various cytokines, growth factors, and extracellular matrix components. Targeting TME using targeted drug delivery and nanoparticles is an attractive strategy for the treatment of solid tumors and recently has received significant research attention under precise medicine concept. TME plays a pivotal role in the overall survival and metastasis of a tumor by stimulating cell proliferation, preventing the tumor clearance by the immune cells, enhancing the oncogenic potential of the cancer cells, and promoting tumor invasion. Hepatocellular Carcinoma (HCC) is one of the major causes of cancer-associated deaths affecting millions of individuals worldwide each year. TCM herbs contain several bioactive phytoconstituents with a broad range of biological, physiological, and immunological effects on the system. Several TCM herbs and their monomers have shown inhibitory effects in HCC by controlling the TME. This study reviews the fundamentals and applications of targeting strategies for immunosuppressing TME to treat cancers. This study focuses on TME targeting strategies using TCM herbs and the molecular mechanisms of several TCM herbs and their monomers on controlling TME.
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Nanoformulation of lactoferrin potentiates its activity and enhances novel biotechnological applications.
El-Fakharany, EM
International journal of biological macromolecules. 2020;(Pt A):970-984
Abstract
Lactoferrin is a glycoprotein with a molecular weight of 80 kDa, which produced in many mammalian excretions. LF is involved in various physiological processes and known to possess prominent biocidal activities, serving as an effective agent against a wide range of pathogens. This effective biocidal activity of LF in association with immune system response has made this protein an attractive therapeutic candidate. Interaction of proteins with nanoparticles (NPs) gives rise to the formation of a dynamic NP-protein complex and can induce conformational changes in the adsorbed proteins which may lead to the change in their function. With the recent advances in nanotechnology, NPs may provide the protection and stabilization of LF from hydrolysis by some proteases and increase their uptake by targeted cells. These nanoformulations of LF can be used as diagnosis, disease targeting and drug delivery tools. Owing to its multiple functionalities, LF is a promising active ingredient to be loaded or adsorbed to NPs for preparing a stable, controlled surface NPs. Thus, LF NPs can potentially empower the resulting nanocomplex with attracting functionalities and might be useful in many applications, e.g., to modify the optical or rheological properties of products, or to encapsulate and deliver bioactive ingredients.
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Ovalbumin-modified nanoparticles increase the tumor accumulation by a tumor microenvironment-mediated "giant".
Zhou, J, Geng, S, Wang, Q, Yin, Q, Lou, R, Wei, L, Wu, Y, Du, B, Yao, H
Journal of materials chemistry. B. 2020;(33):7528-7538
Abstract
We designed a pH intelligently driven self-assembled nano-platform (GOx@ZIF-OVA). The nano-platform was composed of glucose oxidase (GOx), ovalbumin (OVA) and zeolitic imidazolate skeleton-8 (ZIF-8). The goal was to address the depth and cumulative limits of the drug at the tumor site. Firstly, OVA-modified GOx@ZIF could greatly increase tumor accumulation due to spontaneous self-assembly from 142.2 ± 9.1 to 705.5 ± 52.1 nm and the 5779.4 ± 598.3 nm giant at pH values of 7.4, 6.5, and 5.0, respectively. More importantly, the tumor-like sphere experiments demonstrated that the encapsulated GOx "vampires" can cut off the energy source of tumors and poisonous tumor cells without depth limitations. Furthermore, immunofluorescence assay and cytotoxicity assay tests in vivo proved that T cell infiltration could be significantly increased, triggering an effective anti-tumor immune response and inhibiting lung metastasis. Therefore, the experimental results demonstrated that the acid-smart-driven nano-platform has the potential to address the limitations of tumor depth and drug accumulation in solid tumors.
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Biodegradable Polymeric Nanoparticles for Therapeutic Cancer Treatments.
Karlsson, J, Vaughan, HJ, Green, JJ
Annual review of chemical and biomolecular engineering. 2018;:105-127
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Abstract
Polymeric nanoparticles have tremendous potential to improve the efficacy of therapeutic cancer treatments by facilitating targeted delivery to a desired site. The physical and chemical properties of polymers can be tuned to accomplish delivery across the multiple biological barriers required to reach diverse subsets of cells. The use of biodegradable polymers as nanocarriers is especially attractive, as these materials can be designed to break down in physiological conditions and engineered to exhibit triggered functionality when at a particular location or activated by an external source. We present how biodegradable polymers can be engineered as drug delivery systems to target the tumor microenvironment in multiple ways. These nanomedicines can target cancer cells directly, the blood vessels that supply the nutrients and oxygen that support tumor growth, and immune cells to promote anticancer immunotherapy.
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Crosstalk between core-multishell nanocarriers for cutaneous drug delivery and antigen-presenting cells of the skin.
Edlich, A, Volz, P, Brodwolf, R, Unbehauen, M, Mundhenk, L, Gruber, AD, Hedtrich, S, Haag, R, Alexiev, U, Kleuser, B
Biomaterials. 2018;:60-70
Abstract
Owing their unique chemical and physical properties core-multishell (CMS) nanocarriers are thought to underlie their exploitable biomedical use for a topical treatment of skin diseases. This highlights the need to consider not only the efficacy of CMS nanocarriers but also the potentially unpredictable and adverse consequences of their exposure thereto. As CMS nanocarriers are able to penetrate into viable layers of normal and stripped human skin ex vivo as well as in in vitro skin disease models the understanding of nanoparticle crosstalk with components of the immune system requires thorough investigation. Our studies highlight the biocompatible properties of CMS nanocarriers on Langerhans cells of the skin as they did neither induce cytotoxicity and genotoxicity nor cause reactive oxygen species (ROS) or an immunological response. Nevertheless, CMS nanocarriers were efficiently taken up by Langerhans cells via divergent endocytic pathways. Bioimaging of CMS nanocarriers by fluorescence lifetime imaging microscopy (FLIM) and flow cytometry indicated not only a localization within the lysosomes but also an energy-dependent exocytosis of unmodified CMS nanocarriers into the extracellular environment.
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The pathogenicity of Aspergillus fumigatus, drug resistance, and nanoparticle delivery.
Szalewski, DA, Hinrichs, VS, Zinniel, DK, Barletta, RG
Canadian journal of microbiology. 2018;(7):439-453
Abstract
The genus Aspergillus includes fungal species that cause major health issues of significant economic importance. These microorganisms are also the culprit for production of carcinogenic aflatoxins in grain storages, contaminating crops, and economically straining the production process. Aspergillus fumigatus is a very important pathogenic species, being responsible for high human morbidity and mortality on a global basis. The prevalence of these infections in immunosuppressed individuals is on the rise, and physicians struggle with the diagnosis of these deadly pathogens. Several virulence determinants facilitate fungal invasion and evasion of the host immune response. Metabolic functions are also important for virulence and drug resistance, since they allow fungi to obtain nutrients for their own survival and growth. Following a positive diagnostic identification, mortality rates remain high due, in part, to emerging resistance to frequently used antifungal drugs. In this review, we discuss the role of the main virulence, drug target, and drug resistance determinants. We conclude with the review of new technologies being developed to treat aspergillosis. In particular, microsphere and nanoparticle delivery systems are discussed in the context of improving drug bioavailability. Aspergillus will likely continue to cause problematic infections in immunocompromised patients, so it is imperative to improve treatment options.
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An Appraisal on Various Methods of Nano Particulate Formulations.
Dhiman, B, Divtrannum, , Dhiman, A, Saini, S
Pharmaceutical nanotechnology. 2017;(4):255-262
Abstract
BACKGROUND Nanotechnology has immense significance in the field of medicine, agriculture, business, public health sector due to wide applicability of the nano products. Basically, nanotechnology is the incorporation of nanoscale structures into larger material components to improve the properties of constructed system. METHOD Nanotechnology serves as an alternative drug delivery system to the liposomes drug delivery system as the stability of the product in biological fluids is the main problem associated with the liposomal drug delivery system. In the present review, nanoparticles, their applications, various techniques of preparation of nanoparticles and research update on nano particulate drug delivery system have been discussed. RESULTS The main complication associated with biodegradable polymer is uncertainty in their absorption pathway in gastrointestinal tract. Sometimes, harmful by-products after metabolism are released. However, the polymeric nanoparticles (synthetic or semi-synthetic) have a defined structure therefore; get absorbed in intact form in gastrointestinal tract. CONCLUSION Nano-particulate drug delivery system using natural/synthetic polymer may enhance the therapeutic activity of some anti-cancer drug by increasing the host's immune mechanism and antitumor role through improving the body's immune function. It has been observed that despite the technological challenges, nanoparticulate drug delivery system is the most promising drug delivery system in case of anticancer drugs because polymer based nanostructures enhance the bio-adhesiveness and as well as local accumulation of chemotherapeutic agent.
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Harnessing self-assembled peptide nanoparticles in epitope vaccine design.
Negahdaripour, M, Golkar, N, Hajighahramani, N, Kianpour, S, Nezafat, N, Ghasemi, Y
Biotechnology advances. 2017;(5):575-596
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Abstract
Vaccination has been one of the most successful breakthroughs in medical history. In recent years, epitope-based subunit vaccines have been introduced as a safer alternative to traditional vaccines. However, they suffer from limited immunogenicity. Nanotechnology has shown value in solving this issue. Different kinds of nanovaccines have been employed, among which virus-like nanoparticles (VLPs) and self-assembled peptide nanoparticles (SAPNs) seem very promising. Recently, SAPNs have attracted special interest due to their unique properties, including molecular specificity, biodegradability, and biocompatibility. They also resemble pathogens in terms of their size. Their multivalency allows an orderly repetitive display of antigens on their surface, which induces a stronger immune response than single immunogens. In vaccine design, SAPN self-adjuvanticity is regarded an outstanding advantage, since the use of toxic adjuvants is no longer required. SAPNs are usually composed of helical or β-sheet secondary structures and are tailored from natural peptides or de novo structures. Flexibility in subunit selection opens the door to a wide variety of molecules with different characteristics. SAPN engineering is an emerging area, and more novel structures are expected to be generated in the future, particularly with the rapid progress in related computational tools. The aim of this review is to provide a state-of-the-art overview of self-assembled peptide nanoparticles and their use in vaccine design in recent studies. Additionally, principles for their design and the application of computational approaches to vaccine design are summarized.