Efficient tumor targeting by polysaccharide decked polyethylenimine based nanocomposites.
Hyaluronic acid (HA)-polyethylenimine (PEI, 25 kDa) (HP) nanocomposites were fabricated for efficient targeting to solid tumors. Branched PEI was ionically blended with a natural mucopolysaccharide, HA, to partially block the positive charge and to impart site specificity to HP nanocomposites. A series of nanocomposites were prepared by varying the content of HA. HP nanocomposites were characterized by their size, morphology, zeta potential and evaluated for pDNA protection study, transfection efficiency and cytotoxicity. The competency of HP nanocomposites to relocate a plasmid encoding enhanced green fluorescent protein (pEGFP) gene was assessed in HEK293, HEK293T, and HeLa cells and found to be approximately 1-8 folds efficient compared to Superfect, Fugene, GenePORTER 2. HP nanocomposites also exhibited efficient transfection in serum-containing medium. MTT assay showed significantly improved cell viability in HEK293T, HepG2 and HeLa cells. The specificity of HP nanocomposites to target tumor was investigated in vivo by injecting pDNA-loaded HP-4 nanocomposite or PEI intravenously into mice bearing Ehrlich ascites tumor (EAT). The gamma scintigraphic studies showed a higher accumulation of HP-4 nanocomposite in the solid tumor compared to PEI. The results cumulatively advocate that HP nanocomposites could epitomize a viable alternative for site specific gene therapy.
Pathak
Atul
A
Institute of Genomics and Integrative Biology (CSIR), Delhi University Campus, Mall Road, Delhi 110007, India.
Swami
Archana
A
Patnaik
Soma
S
Jain
Sanyog
S
Chuttani
Krishna
K
Mishra
Anil K
AK
Vyas
Suresh P
SP
Kumar
Pradeep
P
Gupta
Kailash C
KC
D004247:DNA / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D017886:Durapatite / Q000737:chemistry / Q000493:pharmacokinetics*; D018390:Gene Targeting / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D049329:Nanostructures / Q000737:chemistry*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry* / Q000493:pharmacokinetics; D014162:Transfection / Q000379:methods*
D011134:Polysaccharides; D011094:Polyethyleneimine; D004247:DNA; D017886:Durapatite