Surface modified cellulose nanocrystalline hybrids actualizing efficient and precise delivery of doxorubicin into nucleus with: In vitro and in vivo evaluation

Abstract Rod‐like‐shape nanomedicines with the ability of lysosomal pH‐controlled drug release can precisely deliver doxorubicin (DOX) into its target, nucleus, and can fully exert its anticancer effect. Taking advantage of their large specific surface area, cellulose nanocrystals (CNCs) were used to fabricate pH‐responsive DOX‐loaded rod‐like shaped hybrids nanomedicines: cis ‐aconityl‐doxorubicin (CAD)@polyethylenimine (PEI)@CNCs (CAD@PEI@CNCs) via layer‐by‐layer (LbL) assembly. In vitro, CAD@PEI@CNCs hybrids displayed rod‐like shape, high drug loading content, lysosomal pH‐controlled drug release, efficient and precise doxorubicin (DOX) delivering into the nucleus. Moreover, the cellular uptake of CAD@PEI@CNCs hybrids was 20.9 folds higher than that of DOX·HCl against A549 cells. The cytotoxicity of CAD@PEI@CNCs hybrids was much higher than that of DOX·HCl and the pH‐irresponsive hybrids against A549 cell. In vivo, CAD@PEI@CNCs hybrids exhibited good antitumor effect: (42.0 ± 6)% inhibition rate and few harms to the nude mice. Altogether, rod‐like shaped pH‐responsive CAD@PEI@CNCs hybrids nanomedicines could efficiently overcome the vascular and tumor barriers, and precisely deliver DOX to nucleus to convert DOX antitumor effects. These results indicate that CAD@PEI@CNCs have great potential to act as advanced nanomedicines with enhanced delivery efficiency and therapeutic efficiency.