Single-walled carbon nanotube-conjugated chemotherapy exhibits increased therapeutic index in melanoma.
The incidence of malignant melanoma is increasing at an alarming rate globally. Poor prognosis and extraordinarily low survival rates of malignant melanoma necessitates the development of new chemotherapeutic strategies. An emerging approach is to harness nanotechnology to optimize the existing chemotherapies. In the present study we have demonstrated that the delivery of doxorubicin using a nanotechnology-based platform significantly reduces the systemic toxicity of the drug, keeping unchanged its therapeutic efficacy in a mouse melanoma tumor model. Specifically we modified single-walled carbon nanotubes (CNTs) to conjugate a doxorubicin prodrug via a carbamate linker that cleaves enzymatically to cause temporal release of the active drug. The CNT-doxorubicin conjugate (CNT-Dox) induced time-dependent cell death in B16-F10 melanoma cells in vitro. The nanoparticle was rapidly internalized into the lysosome of melanoma cells and was retained in the subcellular compartment for over 24 h. In an in vivo melanoma model, treatment with the nanotube-doxorubicin conjugate abrogated tumor growth without the systemic side-effects associated with free doxorubicin. Our studies demonstrate that a simple and versatile CNT-based nanovector can be harnessed for the delivery of chemotherapy to melanoma, with increased therapeutic index.
Chaudhuri
Padmaparna
P
BWH-HST Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
Soni
Shivani
S
Sengupta
Shiladitya
S
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D003460:Crystallization / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D046911:Macromolecular Substances / Q000737:chemistry; D008422:Materials Testing; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008968:Molecular Conformation; D050997:Nanomedicine / Q000379:methods; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000648:ultrastructure; D013499:Surface Properties; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D004337:Drug Carriers; D046911:Macromolecular Substances; D037742:Nanotubes, Carbon; D004317:Doxorubicin