as-1411 and Skin-Neoplasms

Malignant melanoma accounts for about 1% of all skin malignant tumors and represents the most aggressive and lethal form of skin cancer. Clinically, there exist different therapeutic options for melanoma treatment, such as surgery, chemotherapy, radiotherapy, photodynamic therapy and immunotherapy. However, serious adverse effects usually arise, and survival rates are still low because a high number of patients present relapses within 6-9 months after therapy. AS1411 is a G-quadruplex (G4) aptamer capable of tumor-specific recognition, since it binds to nucleolin, a multi-functional protein expressed in many different types of cancer cells. In this work, we present a novel drug delivery system composed of AS1411 and indocyanine green (ICG) to track its accumulation in tumoral cells in a melanoma mouse model. Using a simple supramolecular strategy, we conjugated the complex AS1411-ICG with C

Topics: Animals; Aptamers, Nucleotide; Cell Survival; Dose-Response Relationship, Drug; Drug Delivery Systems; Female; Humans; Indocyanine Green; Melanoma; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Oligodeoxyribonucleotides; Skin Neoplasms

BRAF gene mutation is found in more than 60% of malignant melanomas, which are difficult to treat. In this study, a new tumor-targeting liposome was developed to deliver anti-BRAF siRNA (siBraf) for the treatment of melanomas. Nucleolin is overexpressed on the surface of cancer cells. AS1411, an aptamer showing specific binding to nucleolin, was conjugated to PEGylated cationic liposome as the targeting probe ASLP (AS1411-PEG-liposome). The ASLP/siRNA complex was formed through electrostatic interaction between ASLP and siRNA. The binding of AS1411 to the surface of PEGylated liposomes was confirmed by gel electrophoresis and capillary electrophoresis. Real-time PCR and Western blot analysis showed that ASLP/siBraf exhibited strong silencing activity of BRAF gene. The much higher accumulation of the siRNA in tumor cells comparing with normal cells indicated that ASLP displayed excellent tumor-targeting capability. Notably, ASLP/siBraf showed significant silencing activity in A375 tumor xenograft mice and inhibited the melanoma growth. These results suggested that the new nucleolin-targeted siRNA delivery system by AS1411 may have the potential for the treatment of melanoma.

Topics: Aptamers, Nucleotide; Blotting, Western; Drug Carriers; Electrophoresis, Capillary; Electrophoresis, Polyacrylamide Gel; Humans; Liposomes; Melanoma; Microscopy, Electron, Transmission; Nucleolin; Oligodeoxyribonucleotides; Phosphoproteins; Real-Time Polymerase Chain Reaction; RNA-Binding Proteins; RNA, Small Interfering; Skin Neoplasms