Document Detail

Poly(β-amino ester) nanoparticle delivery of TP53 has activity against small cell lung cancer in vitro and in vivo.
MedLine Citation:
PMID:  23364678     Owner:  NLM     Status:  MEDLINE    
Small cell lung cancer (SCLC) is an aggressive disease with one of the highest case-fatality rates among cancer. The recommended therapy for SCLCs has not changed significantly over the past 30 years; new therapeutic approaches are a critical need. TP53 is mutated in the majority of SCLC cases and its loss is required in transgenic mouse models of the disease. We synthesized an array of biodegradable poly(β-amino ester) (PBAE) polymers that self-assemble with DNA and assayed for transfection efficiency in the p53-mutant H446 SCLC cell line using high-throughput methodologies. Two of the top candidates were selected for further characterization and TP53 delivery in vitro and in vivo. Nanoparticle delivery of TP53 resulted in expression of exogenous p53, induction of p21, induction of apoptosis, and accumulation of cells in sub-G1 consistent with functional p53 activity. Intratumoral injection of subcutaneous H446 xenografts with polymers carrying TP53 caused marked tumor growth inhibition. This is the first demonstration of TP53 gene therapy in SCLC using nonviral polymeric nanoparticles. This technology may have general applicability as a novel anticancer strategy based on restoration of tumor suppressor gene function.
Chandrashekhar D Kamat; Ron B Shmueli; Nick Connis; Charles M Rudin; Jordan J Green; Christine L Hann
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-30
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  12     ISSN:  1538-8514     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-10     Completed Date:  2013-10-22     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  405-15     Citation Subset:  IM    
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MeSH Terms
Cell Cycle / genetics
Cell Line, Tumor
Disease Models, Animal
Gene Expression
Gene Transfer Techniques*
Genes, p53*
Lung Neoplasms / genetics*,  pathology
Nanoparticles / chemistry*
Polymers / chemistry*
Small Cell Lung Carcinoma / genetics*,  pathology
Tumor Burden / genetics
Xenograft Model Antitumor Assays
Grant Support
Reg. No./Substance:
0/Polymers; 0/poly(beta-amino ester)

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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