SYSTÈME DE LIBÉRATION DE MÉDICAMENT DÉPENDANT DE LA FORCE POUR AMÉLIORER LA DESTRUCTION SÉLECTIVE ET RÉDUIRE AU MINIMUM LES EFFETS INDÉSIRABLES DANS LE TRAITEMENT DU CANCER
The disclosure provides a force-dependent drug release system. The system is configured such that the drug is only released and subsequently internalized by cancer cells, which exert at least a threshold amount of force on a DNA component of the system. The system includes a tension sensor that is used to release a chemotherapeutic agent selectively into cancer cells. The system includes a first nucleic acid single strand of DNA or DNA analog that is conjugated to a substrate, and a second nucleic acid single strand of DNA or DNA analog that is hybridized to the first single strand. The second single strand is conjugated to a cytotoxic molecule that includes a cell surface receptor ligand and a chemotherapeutic agent. The second single strand is not conjugated to the substrate. Also provided are cancer cells that display a surface receptor ligand that is bound to the cytotoxic molecule. Also provided are one or more cancer cells that have internalized a single strand conjugated to the cytotoxic molecule, but have not internalized the first strand. Also provided are methods of treating cancer by administering the system The disclosure also provides a method for treating cancer by administering to an individual in need thereof. Also provided is a method for screening or testing chemotherpeutic agents for use in the system.La présente invention concerne un système de libération de médicament dépendant de la force. Le système est configuré de sorte que le médicament soit uniquement libéré et ensuite internalisé par des cellules cancéreuses, qui exercent au moins une quantité de seuil de force sur un composant d'ADN du système. Le système comprend un capteur de tension qui est utilisé pour libérer un agent chimiothérapeutique sélectivement dans des cellules cancéreuses. Le système comprend un premier brin individuel d'acide nucléique d'ADN ou d'analogue d'ADN qui est conjugué à un substrat, et un deuxième brin unique d'acide nucléique d'ADN ou d'analogue d'ADN qui est hy