Purpose: To determine whether -CONH-(CH2)6-NH3+Cl− functionalized single-walled carbon nanotubes (SWNT) carrying complexed small interfering RNA (siRNA) can enter into tumor cells, wherein they release the siRNA to silence the targeted gene. Experimental Design: -CONH-(CH2)6-NH3+Cl− was used to mediate the conjugation of telomerase reverse transcriptase (TERT) siRNA to SWNTs. The ability of TERT siRNA delivered via SWNT complexes to silence the expression of TERT was assessed by their effects on the proliferation and growth of tumor cells both in vitro and in mouse models. Results: The functionalized SWNTs -CONH-(CH2)6-NH3+Cl− could facilitate the coupling of siRNAs that specifically target murine TERT expression to form the mTERT siRNA:SWNT+ complex. These functionalized SWNTs rapidly entered three cultured murine tumor cell lines, suppressed mTERT expression, and produced growth arrest. Injection of mTERT siRNA:SWNT+ complexes into s.c. Lewis lung tumors reduced tumor growth. Furthermore, human TERT siRNA:SWNT+ complexes also suppressed the growth of human HeLa cells both in vitro and when injected into tumors in nude mice. Conclusions: -CONH-(CH2)6-NH3+Cl− functionalized SWNTs carry complexed siRNA into tumor cells, wherein they release the siRNA from the nanotube sidewalls to silence the targeted gene. The -CONH-(CH2)6-NH3+Cl− functionalized SWNTs may represent a new class of molecular transporters applicable for siRNA therapeutics.
Delivery of Telomerase Reverse Transcriptase Small Interfering RNA in Complex with Positively Charged Single-Walled Carbon Nanotubes Suppresses Tumor Growth
Zhuohan Zhang,Xiaoying Yang,Yuan Zhang,B. Zeng,Shujing Wang,T. Zhu,R. Roden,Yongsheng Chen,Rongcun Yang
Published 2006 in Clinical Cancer Research
ABSTRACT
PUBLICATION RECORD
- Publication year
2006
- Venue
Clinical Cancer Research
- Publication date
2006-08-15
- Fields of study
Biology, Medicine, Chemistry, Engineering
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- hela cells
A human cervical cancer cell line used here to test siRNA delivery and growth inhibition.
Aliases: HeLa
- human tert sirna:swnt+ complex
A conjugate of human telomerase reverse transcriptase siRNA with positively charged single-walled carbon nanotubes.
Aliases: hTERT siRNA:SWNT+, human TERT siRNA-SWNT+
- lewis lung tumors
Subcutaneous mouse tumors derived from Lewis lung cancer cells and used as an in vivo tumor model.
Aliases: Lewis lung carcinoma tumors, s.c. Lewis lung tumors
- mtert sirna:swnt+ complex
A conjugate of murine telomerase reverse transcriptase siRNA with positively charged single-walled carbon nanotubes.
Aliases: mTERT siRNA-SWNT+, murine TERT siRNA:SWNT+ complex
- nude mice
Immunodeficient mice used as hosts for human tumor xenografts in the in vivo experiments.
Aliases: nude mouse model
- positively charged single-walled carbon nanotubes
Single-walled carbon nanotubes functionalized with positively charged side groups used as the siRNA carrier in this work.
Aliases: SWNT+, -CONH-(CH2)6-NH3+Cl− functionalized SWNTs
- tert sirna
Small interfering RNA designed to target telomerase reverse transcriptase transcripts in the experiments.
REFERENCES
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