Self-Assembly of an Aptamer-Decorated, DNA–Protein Hybrid Nanogel: A Biocompatible Nanocarrier for Targeted Cancer Therapy

Abstract

Nanocarrier-based chemotherapy is one of the most efficient approaches for the treatment of cancer, and hence, the design of new nanocarriers is very important. Herein, the design of a new class of physically cross-linked nanoparticles (nanogel) solely made of biomolecules including DNA, protein, and biotin as a nanocarrier for the targeted cancer therapy is reported. A specific molecular recognition interaction between biotin and streptavidin is explored for the cross-linking of a DNA nanostructure for the crafting of a nanogel. The most unique structural features of nanogels include the following: (i) excellent biocompatibility, (ii) decoration of the nanogel surface with biotin and streptavidin randomly that allowed the integration of aptamer DNA onto the surface of the nanostructure through the biotin-streptavidin interaction, (iii) high doxorubicin encapsulation efficacy through the intercalation of doxorubicin inside the DNA duplex, and (iv) stimuli responsiveness. The selective uptake of a doxorubicin-loaded nanogel by aptamer-receptor-positive cell lines (CCRF-CEM and HeLa) and its delivery inside the target cells are demonstrated. The selective uptake of the nanogel by CCRF-CEM and HeLa cells is attributed to the specific interaction between the aptamer DNA decorated on the surface of the nanogel with the PTK7 receptor overexpressed on CCRF-CEM and HeLa cell lines. These results imply that the nanogel obtained from the self-assembly of biomolecules would be ideal for the crafting of nanocarriers for targeted cargo delivery applications.