Probing the cell delivery of synthetic diubiquitin chains

Abstract

In this study, the live-cell delivery of structurally different synthetic diubiquitin chains was examined.

Drug delivery using biocompatible covalent organic frameworks (COFs) towards a therapeutic approach

“…123 Thus, lysosomal escape is necessary, which is possible using several pathways, where one idea is to introduce enough positive charge on the surface of COFs via post-synthetic modification. 125…”

“…It is known that the cell surface is negatively charged; and thus a positively charged entity may have easier cell penetration, however, the authors suggested that the negative charges on the nanocomposites favoured efficient cell permeability. 123–128 The combined anti-tumour drug delivery of IR783 (achieved by 5 min of 808 nm laser irradiation) was found to be the most effective in terms of cell viability studied by propidium iodide staining. The combination therapy for COF@IR783@CAD with a laser revealed the inhibition of tumour growth in mice.…”

“…However, detailed investigations into the toxicity of COFs such as neurotoxicity, hemocompatibility, genotoxicity, their impacts on the reproductive system, and level of carcinogenicity are highly necessary to explore before they are used as carriers for in vivo application; and (e) drug loading is usually performed in hexane, DCM or DMF medium, which are potentially toxic to cells; instead, DMSO will be more biologically friendly. [123][124][125] Consequently, several steps can be prioritized during the design of future probes based on next-generation COFs:…”

“…123 Thus, lysosomal escape is necessary, which is possible using several pathways, where one idea is to introduce enough positive charge on the surface of COFs via postsynthetic modification. 125 (B) The cell surface is known to be negatively charged, and hence drug@COF with a positive charge on it surface will be helpful for internalization. 125,126,128 However, if the COF is positively charged from the beginning, there may be a problem/issue with the drug loading within the supercharged particle.…”

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Scheme 3 Degradation of drug-loaded COFs within the lysosomal compartment, a possible drawback of lysosomal delivery. [123][124][125] The image was adapted from https://BioRender.com.

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