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.

Design, Bioanalytical, and Biomedical Applications of Aptamer-Based Hydrogels

“…DOX was successively intercalated into the base pairs of CpG-MUC1-hydrogel to form the CpG-MUC1-hydrogel/Dox that would controllably release DOX and CpGs at acidic conditions ( Figure 5A). Moreover, a new class of physically cross-linked nanogel based on DNA, protein, and biotin as a nanocarrier using for the targeted cancer therapy was reported (162). The specific molecular recognition interaction between biotin and streptavidin was used to explore the cross-linking of a nanogel.…”

“…Biotin-modified ssDNAs were assembled to form 5 ′ -biotin-tethered X-shaped branched DNA acting as a tetravalent host and then streptavidin-modified aptamer DNAs interacted with them to form the aptamer-based hydrogels which allowed the loading of doxorubicin inside the gel network and delivered in the cancerous environment. The aptamer-functionalized and doxorubicin-loaded nanogels exhibited selective uptake into target cell lines (162). In the clinical treatment of tumors, the delivery of drugs or genes, nanogels nanocarriers need long term circulation in the blood, enhanced permeability and retention effect (EPR effect), enrichment, infiltration, uptake, and release of the drug or gene.…”

Nucleic Acid Hybrids as Advanced Antibacterial Nanocarriers

“…These DNA-protein conjugate systems can be achieved via non-covalent (e.g., biotin-streptavidin, nickel-nitrilotriacetic acid-hexahistidine and antibody-hapten interactions) or covalent strategies (e.g., disulfide or maleimide coupling and biorthogonal chemistry) using proteins such as streptavidin, antibodies, zinc finger proteins and engineered proteins containing His-, Snap-and Halo-tags [81,90]. In designing nucleic acid-protein hybrid nanocarriers, incorporating recognized multifunctional features such as stimuli responsiveness (to both nucleases and proteases), excellent biocompatibility and integration of targeting moieties (to drive cellular specificity) is highly attractive for anticancer [67] and antimicrobial therapeutics.…”

Polymer Nanoparticles and Nanomotors Modified by DNA/RNA Aptamers and Antibodies in Targeted Therapy of Cancer

“…Therefore, the cargo that delivers the chemotherapeutic drug should selectively recognize the cancer cells. It is well established that various cancer markers are over expressed at the cancer cell membranes, for example protein tyrosine kinase 7 (PTK7) in HeLa cells isolated from cervical cancer [ 25 ]. Thus, modification of the nanostructures such as nanoparticles or nano/micromotors by receptors that can recognize these cancer cells, is of high advantage for targeted drug delivery.…”