Development of a rapid-onset, acid-labile linkage polyplex-mixed micellar system for anticancer therapy was written by Hung, Shiou-Fen;Wen, Yu-Han;Yu, Lu-Yi;Chiu, Hsin-Cheng;Chiang, Yi-Ting;Lo, Chun-Liang. And the article was included in Polymers (Basel, Switzerland) in 2021.Electric Literature of C8H10ClNO3 The following contents are mentioned in the article:
In the treatment of cancers, small interfering ribonucleic acids (siRNAs) are delivered into cells to inhibit the oncogenic protein′s expression; however, polyanions, hydrophilicity, and rapid degradations in blood, endosomal or secondary lysosomal degradation hamper clinal applications. In this study, we first synthesized and characterized two copolymers: methoxy poly(ethylene glycol)-b-poly(2-hydroxy methacrylate-ketal-pyridoxal) and methoxy poly(ethylene glycol)-b-poly(methacrylic acid-co-histidine). Afterwards, we assembled two polymers with the focal adhesion kinase (FAK) siRNA, forming polyplex-mixed micelles for the treatment of the human colon cancer cell line HCT116. In terms of the physiol. condition, the cationic pyridoxal mols. that were conjugated on the copolymer with ketal bonds could electrostatically attract the siRNA. Addnl., the pyridoxal could form a hydrophobic core together with the hydrophobic deprotonated histidine mols. in the other copolymer and the hydrophilic polyethylene glycol (PEG) shell to protect the siRNA. In an acidic condition, the pyridoxal would be cleaved from the polymers due to the breakage of the ketal bonds and the histidine mols. can simultaneously be protonated, resulting in the endosome/lysosome escape effect. On the basis of our results, the two copolymers were successfully prepared and the pyridoxal derivatives were identified to be able to carry the siRNA and be cleavable by the copolymers in an acidic solution Polyplex-mixed micelles were prepared, and the micellar structures were identified. The endosome escape behavior was observed using a confocal laser scanning microscopy (CLSM). The FAK expression was therefore reduced, and the cytotoxicity of siRNA toward human colon cancer cells was exhibited, rapidly in 24 h. This exceptional anticancer efficiency suggests the potential of the pH-sensitive polyplex-mixed micellar system in siRNA delivery. This study involved multiple reactions and reactants, such as 3-Hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde hydrochloride (cas: 65-22-5Electric Literature of C8H10ClNO3).
3-Hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde hydrochloride (cas: 65-22-5) belongs to alcohols. Alcohols are weak acids. The most acidic simple alcohols (methanol and ethanol) are about as acidic as water, and most other alcohols are somewhat less acidic. Tertiary alcohols cannot be oxidized at all without breaking carbon-carbon bonds, whereas primary alcohols can be oxidized to aldehydes or further oxidized to carboxylic acids.Electric Literature of C8H10ClNO3
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts