Novel biodegradable HSAM nanoparticle for drug delivery.
The systemic pharmacological treatment of disease is limited by severe toxicity to normal organs/tissue. Therefore, various delivery vehicles have been designed to carry therapeutic drugs to their target tissues. We designed a novel vehicle formed by the interaction of biotins in a DNA (polymer) with avidins (crosslink), resulting in a porous particle. This self-assembled (HSAM) nanoparticle vehicle has been tested in our laboratory both in vitro and in vivo for its ability to carry doxorubicin, a widely used anticancer drug with a high toxicity to normal organs. Doxorubicin binds to the nanoparticle by intercalating into the DNA strands that are later degraded by nucleases released from cancer cells. Our results showed that 1.1 microg of HSAM DNA can carry 1 microg of doxorubicin, and the doxorubicin-bound HSAM nanoparticle can still be degraded by nucleases (BAL-31 and DNase I). The HSAM nanoparticle carrying doxorubicin can efficiently inhibit cancer cell growth in vitro and in a murine model. Furthermore, this nanoparticle is able to deliver up to 180 ng/mg of doxorubicin to the target tumor tissue, which is 15-fold above the systemic toxicity dose (12 mg/kg). These results suggest that the HSAM nanoparticle is both biocompatible and biodegradable, making it a valuable vehicle for drug delivery in cancer treatment.
Liu
Bin
B
Department of Pathology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Jiang
Shiquan
S
Zhang
Wandi
W
Ye
Fei
F
Wang
Yu-Hang
YH
Wu
Josephine
J
Zhang
David Y
DY
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001360:Avidin / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry; D001710:Biotin / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D015552:Injections, Intralesional; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures / Q000737:chemistry*; D016062:Porosity; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D001672:Biocompatible Materials; D001360:Avidin; D001710:Biotin; D004317:Doxorubicin; D004247:DNA