Disclosed herein are compositions comprising nanoparticles comprising a carrier polypeptide and a double-stranded oligonucleotide, wherein the carrier polypeptide comprises a cell-targeting segment, a cell-penetrating segment, and an oligonucleotide-binding segment: and wherein the molar ratio of the carrier polypeptide to the double-stranded oligonucleotide in the nanoparticle composition is less than about 6:1, along with methods of making and using such nanoparticles. Further described are methods of treating a subject with a cancer, such as a chemotherapeutic drug resistant cancer comprising administering to the subject a composition comprising nanoparticles, the nanoparticles comprising a carrier polypeptide comprising a cell-targeting segment, a cell-penetrating segment, and an oligonucleotide-binding segment； a double-stranded oligonucleotide bound to the oligonucleotide-binding segment； and a chemotherapeutic drug bound to the double-stranded oligonucleotide. Also described are pharmaceutical compositions, articles of manufacture, and kits comprising the described nanoparticles.L'invention concerne des compositions comprenant des nanoparticules comportant un polypeptide porteur et un oligonucléotide double brin, le polypeptide porteur comprenant un segment de ciblage cellulaire, un segment de pénétration cellulaire et un segment de liaison oligonucléotidique, et le rapport molaire entre le polypeptide porteur et l'oligonucléotide double brin dans la composition de nanoparticules étant inférieur à environ 6 : 1 ； ainsi que des procédés de fabrication et d'utilisation de telles nanoparticules. L'invention concerne en outre des procédés de traitement d'un sujet atteint d'un cancer, tel qu'un cancer résistant aux médicaments chimiothérapeutiques, ces procédés consistant à administrer à ce sujet une composition comprenant des nanoparticules, ces nanoparticules comportant un polypeptide porteur comprenant un segment de ciblage cellulaire, un segment de pénétration
