1 research outputs found
Cationic Polyphosphazene Vesicles for Cancer Immunotherapy by Efficient in Vivo Cytokine IL-12 Plasmid Delivery
To circumvent the
severe toxicity of the systemic delivery of IL-12
protein and the limits of local administration of IL-12 gene, we constructed
a polymersome system for systemic delivery of recombinant murine IL-12
plasmid (pmIL-12) based on amphiphilic polyphosphazenes containing
weakly cationic N,N-diisopropylethylenediamine (DPA) as hydrophobic
groups and monomethoxy poly(ethylene glycol) (mPEG) as hydrophilic
tails. By simple dialysis method, pmIL-12 was successfully loaded
into polymersomes due to the combination effect of physical encapsulation
and electrostatic interaction. This pmIL-12 polymersome delivery system
was validated with good biocompatibility and stability despite of
serum protein and DNase challenging. The results of in vivo antitumor
experiments showed that intravenous injection of pmIL-12 polymersomes
achieved significant suppression of tumor growth in BALB/c mice bearing
CT-26 colon carcinoma. The analysis revealed that the mechanism was
related to the antitumor immune response induced by efficient transfection
of pmIL-12 polymersomes, which maybe involved lymphocytes infiltration
and angiogenic inhibition at the tumor site