Light-triggered, self-immolative nucleic Acid-drug nanostructures.
The simultaneous intracellular delivery of multiple types of payloads, such as hydrophobic drugs and nucleic acids, typically requires complex carrier systems. Herein, we demonstrate a self-deliverable form of nucleic acid-drug nanostructure that is composed almost entirely of payload molecules. Upon light activation, the nanostructure sheds the nucleic acid shell, while the core, which consists of prodrug molecules, disintegrates via an irreversible self-immolative process, releasing free drug molecules and small molecule fragments. We demonstrate that the nanostructures exhibit enhanced stability against DNase I compared with free DNA, and that the model drug (camptothecin) released exhibits similar efficacy as free, unmodified drugs toward cancer cells.
†Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
Xuyu
X
Tan
§Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02215, United States.|∥Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02215, United States.
Ben B
BB
Li
†Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
Xueguang
X
Lu
†Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
Fei
F
Jia
†Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
Clarissa
C
Santori
†Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
Priyanka
P
Menon
‡Institute of Chemical Biology and Nanomedicine, Hunan University, Changsha 410081, China.
Hui
H
Li
‡Institute of Chemical Biology and Nanomedicine, Hunan University, Changsha 410081, China.
Bohan
B
Zhang
§Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02215, United States.|∥Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02215, United States.
Jean J
JJ
Zhao
†Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.|‡Institute of Chemical Biology and Nanomedicine, Hunan University, Changsha 410081, China.
Ke
K
Zhang
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage*; D004247:DNA / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D008027:Light; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage*
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D011355:Prodrugs; D004247:DNA; D002166:Camptothecin