Oncolytic Adenovirus Complexes Coated with Lipids and Calcium Phosphate for Cancer Gene Therapy.
basic_science · Level V
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- Record sourced from PubMed, PMID 27977128.
- Also identified by DOI 10.1021/acsnano.6b06182.
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Abstract
Oncolytic adenovirus (Onco<sup>Ad</sup>) is a promising therapeutic agent for treating cancer. However, the therapeutic potential of Onco<sup>Ad</sup> is hindered by hepatic sequestration and the host immune response in vivo. Here, we constructed a PEG/Lipids/calcium phosphate (CaP)-Onco<sup>Ad</sup> (PLC-Onco<sup>Ad</sup>) delivery system for ZD55-IL-24, an oncolytic adenovirus that carries the IL-24 gene. The negatively charged PLC-ZD55-IL-24 were disperse and resisted serum-induced aggregation. Compared to naked ZD55-IL-24, the systemic administration of PLC-ZD55-IL-24 in BALB/c mice resulted in reduced liver sequestration and systemic toxicity and evaded the innate immune response. In addition, masking the surface of Onco<sup>Ad</sup> protected it from neutralization by pre-existing neutralizing antibody. PLC-Onco<sup>Ad</sup> achieved efficient targeted delivery in Huh-7-bearing nude mice, and intravenous administration of a high dose of PLC-ZD55-IL-24 increased therapeutic efficacy without inducing toxicity. The developed PLC-Onco<sup>Ad</sup> delivery system represents a promising improvement for oncolytic adenovirus-based cancer gene therapy in vivo.
Medical subject headings
- Calcium Phosphates
- Genetic Therapy
- Genetic Vectors
- Lipids
- Oncolytic Virotherapy