Multi-functional cancer drug delivery nanodevice for precision medicine
Disclosed herein are DNA origami nanostmcture that can be functionalized for personalized and targeted drug delivery. The disclosed nanostructures enter cells through the endolysosomal pathway and circumvent drug resistance mechanisms in target cells. The disclosed nanostructures can be loaded small molecule drugs (e.g. anthracyclines, anti-metabolites) and nucleic acids (e.g. antisense oligonucleotides, siRNA, miRNA) with targeting and/or therapeutic antibodies against tumor-specific antigens (e.g. anti-CD33, anti-CD20) that can be modified to treat to a wide range of cancers and ultimately tailored to specific patients' needs for precision medicine.
1 . A drug delivery device, comprising a DNA origami nanostructure formed from a plurality of DNA scaffold strands and a plurality of DNA staple strands assembled into a rod shape comprising parallel helices and open cavities that extend along the length of the nanostructure,
wherein a small molecule drug is attached to the DNA of the nanostructure,
wherein the nanostructure is conjugated to a plurality of polyethylene glycol (PEG) molecules, and
wherein at least one targeting antibody that selectively binds a tissue or cell antigen is conjugated to an end of the nanostructure.
2 . The device of claim 1 , wherein the small molecule drug is an anthracycline.
3 . The device of claim 2 , wherein the anthracycline comprises doxorubicin, daunorubicin, or idarubicin.
4 . The device of claim 1 , wherein the targeting agent is an antibody that selectively binds a tumor antigen.
5 . The device of claim 1 , wherein the PEG molecules are attached to cationic amino acids.
6 . The device of claim 5 , wherein the PEG molecules are attached to 2, 3, 4, 5, 6, 7, 8, 9, 10, or more lysine residues.
7 . The device of claim 1 , wherein the nanostructure is conjugated to a plurality of oligonucleotides.
8 . The device of claim 1 , wherein the parallel scaffold stands are 5,000 to 10,000 bases in length.
9 . The device of claim 1 , wherein the nanostructure has a quadrilateral cross-section.
10 . The device of claim 1 , comprising at least 24 parallel helices and four open cavities.
11 . The device of claim 7 , wherein at least some of the plurality of oligonucleotides are therapeutic antisense RNA, miRNA, shRNA, RNAi, or siRNA.
12 . The device of claim 7 , wherein at least some of the plurality of oligonucleotides are attached to polyethylene glycol (PEG) molecules.
13 . A method for targeted delivery of a drug to a tissue or cell of a subject, comprising administering to the subject the device of claim 1 .
14 . The method of claim 13 , wherein the subject has cancer, wherein the drug is an anthracycline, and wherein the targeting agent is an antibody that selectively binds a tumor antigen.