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Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Not only is the linker important in the functional sense of physically joining the payload to the antibody, but its precise structure can influence the release rate of the payload which in turn can influence the overall efficacy of an ADC. Ideally, a linker should be robust enough to stay intact while the ADC is circulating in the bloodstream, thus avoiding premature release of the payload and resulting systemic toxicity, but should be designed to cleave specifically at the tumor site thus releasing the cytotoxic agent. For example, linkers have been designed to cleave upon exposure to the enzyme cathepsin which is overexpressed in some tumor cell types. However, it is noteworthy that with this type of construct in which exposure to the cytoplasm within the cell is important, the ADC must be internalized. If internalization does not occur, then the full cytotoxic effect may not be achieved, although some drug may still be released in the vicinity of the tumor.
The Psychological Approach: The Healing Power of Image and Comprehensive Assistance to Cancer Patients
Published in Paloma Tejero, Hernán Pinto, Aesthetic Treatments for the Oncology Patient, 2020
On the other hand, and together with the two previous factors, the family environment and the social group exert an important influence, although finally, the eagerness to reach a certain physical stereotype will depend on the value that each one of us gives to the physical [7], so that we must forget the important role that personal characteristics will play in the construction of this concept. Thus, internalization, which refers to the degree to which ideals at the physical level are accepted, also influences personal assessment [6].
Mechanism of Transfection
Published in Danilo D. Lasic, LIPOSOMES in GENE DELIVERY, 2019
In order for gene expression to occur, DNA plasmid has to enter the cell cytoplasm and migrate into the cell nucleus. The exact mechanism of the internalization is still not clear. Several possibilities, including endocytosis, fusion, and lipid-mediated transmembrane translocation (poration) are discussed. Further studies of these processes are needed to optimize gene delivery systems. The same is true for the entry of DNA plasmid from the cytoplasm into the cell nucleus. In addition to active trafficking de- and recomplexation of DNA with endogenous cationic material may be also important.
‘Poly phenolic phytoceutical loaded nano-bilosomes for enhanced caco-2 cell permeability and SARS-CoV 2 antiviral activity’: in-vitro and insilico studies
Published in Drug Delivery, 2023
Mohamed Y. Zakaria, Shady M. Abd El-Halim, Botros Y. Beshay, Islam Zaki, Mohammed A.S Abourehab
The cellular uptake of RSV Caco-2 cells was evaluated from F5 compared to that of RSV dispersion. Figure 8 revealed that throughout the duration of experiment (120 min), the drug internalization from all samples was increased as the time elapsed. Moreover, after 2 h the uptake of RSV from F5 was significantly (P < 0.05) higher by around 4.7 folds than that of RSV dispersion, 2366.24 ± 135.3 ng/ml 495.65 ± 21.9 ng/ml, respectively. This significant improvement in cellular internalization after formulation was attributed to the tiny PS of the vesicles loaded with the drug, in addition to the components involved in the formulation as bile salts and surfactant exhibited a vital impact on the alteration of cellular membranes permeability (Bapat et al., 2019). Also owing to the capability of the fabricated bilosomes to conjugate either by endocytosis or by fusion to the cells may have accounted for the boosted cellular uptake of the RSV in its F5 formulation. The attachment of the PEGylated vesicles to the cellular membranes increased the concentration and consequent enhancement of the thermodynamic activity gradient of the RSV, thus promoting the permeation ability of lipophilic moieties as RSV (log p = 3.2) (Bapat et al., 2019; Poonia et al., 2020).
Litifilimab (BIIB059), a promising investigational drug for cutaneous lupus erythematosus
Published in Expert Opinion on Investigational Drugs, 2023
Sung Kyung Cho, Thomas Vazquez, Victoria P. Werth
Previous in vitro studies determined that litifilimab binding to BDCA2 led to rapid internalization from the cell membrane as well as colocalization of the BIIB059/BDCA2 complex with downstream effects on TLR 7/9 signaling and inhibition of IFN-1 production [12,43]. The duration of BDCA2 receptor internalization was dose dependent. The average duration of BDCA2 internalization after a single injection of the drug was 14 days at the lowest dose (0.05 mg/kg) in healthy controls and was continuously internalized at the highest dose (20 mg/kg) at the last time point of the study in healthy volunteers (112 days). This indicates that the threshold of circulating litifilimab must be reached (~1 μg/ml) and any concentration lower would not be sufficient to saturate the BDCA2 receptor and lead to BDCA2 returning to the cell membrane.
Macrophage targeted triptolide micelles capable of cGAS-STING pathway inhibition for rheumatoid arthritis treatment
Published in Journal of Drug Targeting, 2022
Alan Xu, Ruoxi Yang, Mingfei Zhang, Xiang Wang, Yuxi Di, Baoping Jiang, Yongxiang Di, Zhanwei Zhou, Lingling Zhou
Cellular internalisation of drugs plays an important role in efficient therapy. Next, we explored cellular uptake of the DL and FDL micelles by using RAW 264.7 cells (a macrophage cell line). The cells were activated by LPS to produce the inflammation statement for M1 polarisation according to a previous report [22], resulting in the increased secretion of cytokines such as TNF-α, IL-1β and IL-6 significantly. To track intracellular micelles, the particles were labelled with Coumarin 6 fluorophore probe, and the location of the cells was visualised by staining the cell nuclei with DAPI. After 4 h incubation, the cell uptake was observed by CLSM. The blue fluorescence represents the nucleus, and the green fluorescence represents the micelles. As shown in Figure 4(A), the fluorescence intensity of DL@C6 group was much weaker than FDL@C6 group for both LPS (−) or LPS (+) cells. It could be ascribed to the folate receptor β (FR-β) targeting ability of FDL@C6 micelles. Moreover, for FDL@C6 group, the fluorescence intensity was significant enhanced for LPS treated cells. It could be ascribed to the upregulation of FR-β in the activated macrophages, which facilitates the cellular uptake of FDL through the specific interaction between FA and FR [45].