Efficient Inhibition of C-26 Colon Carcinoma by VSVMP Gene Delivered by Biodegradable Cationic Nanogel Derived from Polyethyleneimine

Abstract

Biodegradable cationic nanoparticles have promising application as a gene delivery system. In this article, heparin−polyethyleneimine (HPEI) nanogels were prepared, and these nanogels were developed as a nonviral gene vector. The transfection efficiency of HPEI nanogels was comparable with that of PEI25K, while the cytotoxicity was lower than that of PEI2K and much lower than that of PEI25K in vitro. These HPEI nanogels also had better blood compatibility than PEI25K. After intravenous administration, HPEI nanogels degraded, and the degradation products were excreted through urine. The plasmid expressing vesicular stomatitis virus matrix protein (pVSVMP) could be efficiently transfected into C-26 colon carcinoma cells by HPEI nanogels in vitro, inhibiting the cell proliferation through apoptosis induction. Intraperitoneal injection of pVSVMP/HPEI complexes efficiently inhibited the abdominal metastases of C-26 colon carcinoma through apoptosis induction (mean tumor weight in mice treated with pVSVMP/HPEI complex = 0.93 g and in control mice = 3.28 g, difference = 2.35 g, 95% confidence interval [CI] = 1.75−2.95 g, P < 0.001) and prolonged the survival of treated mice. Moreover, intravenous application of pVSVMP/HPEI complexes also inhibited the growth of pulmonary metastases of C-26 colon carcinoma through apoptosis induction. The HPEI nanogels delivering pVSVMP have promising application in treating colon carcinoma.

The enhanced antitumor effects of biodegradable cationic heparin-polyethyleneimine nanogels delivering HSulf-1 gene combined with cisplatin on ovarian cancer

“…The non-viral vectors, such as cationic lipids and polymers have many advantages over viral ones: low immunogenicity, easy to produce and no limitation to the size of transferred DNA molecules, but the toxicity is still a hindrance for the application of non-viral vectors in gene therapy (21,23,24). Polyethylenimine (PEI), one of the most successful and widely studied gene delivery cationic polymers, is effective in gene delivery on account of its condensation of DNA, which facilitates endocytosis, and 'proton sponger' quality, which can prevent DNA from endosomal disruption (25,31). Because PEI is not biodegradable and has the shortcoming of an association between transfection efficiency and cytotoxicity (25,26), in our previous study, the low molecular weight PEI was conjugated chemically into biodegradable cationic nanogels by heparin, to develop a novel gene Figure 5.…”

“…delivery vector (31,32). HPEI nanogels were quickly degraded into low molecular weight PEI followed by excretion through urine in vivo and they also exhibited better blood compatibility, lower cytotoxicity, and stability in vitro, therefore, we used HPEI nanogels as the gene carrier in the present study.…”

“…The biodegradable cationic nanogel-HPEI were synthesized at the State Key Laboratory of Biotherapy and Cancer Center as previously described (31). Brief ly, 50 mg heparin was dissolved in 100 ml 2-N-morpholino ethanesulfonic acid (MES) buffer solution (0.05 M), and then, to activate the carboxylic acid groups of heparin, 20 mg 1-ethyl-3-3-dimethylaminopropyl carbodiimide (EDC) and 30 mg N-hydroxysuccinimide (NHS) were added into the solution.…”

“…Intensive research has been carried out to couple short PEI chains into a longer one using biodegradable linkers to overcome this issue (27)(28)(29)(30). In our previous study, the low molecular weight PEI was chemically conjugated into biodegradable cationic nanogels by heparin and HPEI could serve as a safe and efficient non-viral gene vector (31).…”

Advances in the application of nanotechnology in the diagnosis and treatment of gastrointestinal tumors

“…Kong et al (70) found that IRDye900-conjugated pullulan-cholesterol nanoprobe NIR-PNG exhibited the favorable characteristics of lower dispersion and longer retention in the SLN compared to diluted indocyanine green (ICG) and ICG/poly-γ-glutamic acid complex following injection into the stomachs of dogs and pigs (70). Nanogels may be controlled for various applications in drug delivery and may be tailored to exhibit exceptional stability, low cytotoxicity and higher blood compatibility (71,72). Nanogels containing 5-fluorouracil (5-FU) were developed to be utilized as a new colon-targeting drug carrier systems, owing to their excellent pH-sensitive release property and effectively reduced toxicity (73).…”