Characterization and assessment of nanoencapsulated sanguinarine chloride as a potential treatment for melanoma.
Sanguinarine has a history of use in both folk medicine and early dermatology for the treatment of cutaneous neoplasms. Applied indiscriminately, bloodroot is an escharotic agent with potential to cause extensive tissue necrosis. However, when used in a controlled fashion, sanguinarine imparts selective cytotoxic/anti-proliferative activity through multiple mechanisms against human/ murine melanoma. To exploit sanguinarine's observed activity against melanoma, a targeted delivery system is required. We present a sol-gel based nanoparticulate platform for encapsulating sanguinarine chloride(sang-np)-a targeted therapeutic capable of steady, reliable delivery of predictable quantities of drug over a sustained time period with minimal undesirable effects. Size and release kinetics of sang-np were characterized using dynamic light scattering and ultraviolet-visible spectroscopy respectively. In vitro efficacy of sang-np was assessed. At both 2 and 24 hours, free sanguinarine killed > 90% of B16 melanoma cells, assessed via MTT assay. At 2 hours, sang-np killed a portion of melanoma cells, increasing to percentages comparable to free sanguinarine by 24 hours. Control(empty) nanoparticles exerted minimal toxicity to melanoma cells at both time points. TUNEL assay revealed that treatment with both sanguinarine and sang-np induces apoptosis in B16 melanoma cells, suggesting that both treatments act via the same mechanism of action. These data confirm controlled release of sanguinarine from sang-np, as well as comparable efficacy and mechanism of action to sanguinarine alone. This suggests that nanoparticle delivery of sanguinarine may be a unique approach to capitalize on this potent agent's inherent anti-tumor activity and overcome many of the limitations with its current formulation.
Jamie
J
Rosen
Angelo
A
Landriscina
Brandon L
BL
Adler
Aimee
A
Krauz
Jessica
J
Doerner
Mahantesh
M
Navati
Tagai
T
Musaev
Claudia
C
Gravekamp
Joshua
J
Nosanchuk
Adam J
AJ
Friedman
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053119:Benzophenanthridines / Q000008:administration & dosage* / Q000494:pharmacology; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D000067493:Dynamic Light Scattering; D020287:In Situ Nick-End Labeling; D007546:Isoquinolines / Q000008:administration & dosage* / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D053769:Nanocapsules; D010316:Particle Size; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D003692:Delayed-Action Preparations; D007546:Isoquinolines; D053769:Nanocapsules; C005705:sanguinarine