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Nanodevices for the Detection of Cancer Cells
Published in Suvardhan Kanchi, Rajasekhar Chokkareddy, Mashallah Rezakazemi, Smart Nanodevices for Point-of-Care Applications, 2022
Indeed, various solid tumors possess lower extracellular pH (pH 6.5) as compared to the surrounding tissues (pH 7.5). Thereby selecting the right material composition, it is likely to be possible to engineer nanocarriers that might exploit such pH differences and permit the release of the delivered drugs or genes to the selected target site. pH-sensitive poly(β-amino ester), known as a biodegradable cationic polymer, in an acidic microenvironment experiences a quick dissolution as well as releasing its content all at once, hence it can represent a virtuous scaffold in order to deliver anticancer drugs. Several other strategies include the presence of acid-sensitive spacers such as poly (vinylpyrrolidone-codimethyl maleic anhydride) among the drug and also the polymer, which enables, after endocytosis, drug release in endosomes or lysosomes of tumor cells. In recent scenarios, NPs are called promising vehicles for anti-tumor drug delivery that are designed to be pH-responsive, experiencing physicochemical changes to release enclosed drugs at acidic pH conditions. Thus, if the target is not the lysosome or in general the acidic compartments of the cells, the low pH environment and numerous lysosomal enzymes result in the degradation of endocytosed components, thereby the loss of the therapeutic effect. However, this happens if there are specific mechanisms for the payload in order to escape out of the lysosomes as well as maximize the efficiency of several treatments [99,100].
Multiple biotherapy effects of salidroside on tumors
Published in Domenico Lombardo, Ke Wang, Advances in Materials Science and Engineering, 2021
X.P. Wang, D.Y. Yuan, W.H. Li, Y. Tian
Autophagy refers to the process in which cells phagocytize their own cytoplasm or organelles after receiving some stimulation, and form autophagy bodies through membrane encapsulation, and then autophagy bodiescombine with lysosomes to form autophagic lysosomes. Finally, autophagic lysosomes complete their degradation through internal proteolytic enzymes [25–27]. Autophagy activity changes in a variety of human tumor cells. In recent years, many studies have shown that autophagy plays an important role in the occurrence and development of tumors [25–27]. Inducing or inhibiting autophagy may become an effective anti-cancer method. Autophagy is regulated by a series of autophagy-related genes (ATG) [28]. Becline1 and LC3 are involved in the formation of autophagy, and their expression level is closely related to autophagy ability [29]. LC3 exists in the cytoplasm as the inactive form, LC3-I. When autophagy occurs, LC3-I will be transformed into LC3-Ⅱ and combine with the autophagy membrane to form an autophagic lysosome until it is degraded by lysosomal enzymes. Therefore, the content of LC3-Ⅱ can reflect the level of autophagy in cells. The studyfound that salidroside could induce autophagy in SW1353 cells by up-regulating LC3-II and down-regulating p62 expression[30]. Salidroside can induce autophagy in colon cancer cells, possibly by promoting the expression of LC3-Ⅱ and becline 1 [31].
Polysaccharide-Drug Nanoconjugates as Targeted Delivery Vehicles
Published in Raj K. Keservani, Anil K. Sharma, Rajesh K. Kesharwani, Drug Delivery Approaches and Nanosystems, 2017
The drug loading of high MW alginate-DNM (HMW-alginate-DNM) conjugate was 0.8% w/w compared with 1.3% w/w for the low MW (LMW-alginate-DNM) conjugate. The conjugates contained <1% free DNM in relation to the total DNM content. The drug release from the conjugate was tested in citrate/phosphate buffers of different pH values (5.0, 6.0 and 7.0). At pH 7.0, only 3.1% DNM was released over 48 h. The drug release rate was about 2.5-fold faster at pH 5.0 than that at pH6.0. HMW-alginate-DNM conjugate discharged a maximum of 22.0% and 8.7% at pH 5.0 and6.0, respectively. Unlike HMW-alginate-DNM, LMW-alginate-DNM was found to release a drug derivative in addition to DNM. At pH 5.0, DNM/DNM-derivative was released from LMW-alginate-DNM whereas; the conjugate released only 1.6% loads over 48 h, demonstrating its stability at pH 7.0. A total of 61.9% DNM/DNM-derivative released at pH5.0 after 48 h. The use of rat liver lysosomal enzymes in pH 5.0 buffer did not speed up the release of DNM/DNM derivative.
Genetic variants affecting chemical mediated skin immunotoxicity
Published in Journal of Toxicology and Environmental Health, Part B, 2022
Isisdoris Rodrigues de Souza, Patrícia Savio de Araujo-Souza, Daniela Morais Leme
The FLG monomers take part in SC formation. In this process, FLG monomers bind to keratin filaments, aggregating them into keratin fibrils organized in parallel bundles to form a matrix that provides rigidity to the overall structure, which are the major constituents of corneocytes (Egawa and Kabashima 2018; Norlén and Al-Amoudi 2004). Corneocytes generate a network within a lipid-rich extracellular matrix and produce compaction of keratinocytes. In the process of compacting keratinocytes, corneocytes are denucleated and flattened, and the intercellular space between them filled with lipids from the lamellar bodies (Egawa and Kabashima 2018). Lamellar bodies are membrane-circumscribed granules produced by keratinocytes from SG and contain lipids, corneodesmosin, and kallikreins (Egawa and Kabashima 2018). These lipids are mainly ceramides, free fatty acids, and cholesterol. The secretion of the content of lamellar bodies into the extracellular space enables the covalent attachment of o-hydroxylated ceramides and fatty acids to cornified envelope proteins, forming a lipid-bound envelope (Hill, Paslin, and Wertz 2006). Then, lysosomal enzymes, which need an acidic pH optimum, degrade the polar lipid precursor to hydrophobic ceramides, generating an intact permeability barrier, and is responsible for the acidic pH of the skin (Doering et al. 1999).
Self-assembled supramolecular thermoreversible β-cyclodextrin/ethylene glycol injectable hydrogels with difunctional Pluronic®127 as controlled delivery depot of curcumin. Development, characterization and in vitro evaluation
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Samiullah Khan, Muhammad Usman Minhas, Mahmood Ahmad, Mohammad Sohail
Hydrogels are cross-linked polymeric networks that can be swollen in water, buffered or physiological solutions [4]. These materials can absorb large amounts of water without being dissolved because of the presence of physical or chemical cross linkage of polymer chains [5]. Stimuli-responsive hydrogels have attracted a considerable attention and are being developed at prolific rate as drug carrier systems. These hydrogels contract and relax in response to small changes in the environment of the surrounding medium [6]. Various stimuli responsive materials that show response to either an internal stimulus (e.g. glucose, lysosomal enzymes, pH and redox potential) or external stimulus (e.g. light, magnetic field, temperature and ultrasound waves) have been dynamically developed to achieve site-specific drug release [7–9]. Smart polymeric gels have been used as biosensors, actuators and nanoscale biomedical, devices [10–12]. Temperature is considered to be one of the most extensively used stimulus for developing stimuli responsive hydrogels as it is easily controllable and has many practical benefits both in vitro and in vivo [13,14].