lipofectamine and Head-and-Neck-Neoplasms

Pediatric head and neck cancers account for overall 12% of all pediatric cancers. Despite recent advances in therapeutic modalities, children with tumor metastasis have poor prognosis. Therefore, there is an unmet need for new and effective treatment modalities for pediatric head and neck cancers. The present study describes a simple and efficient method for fabrication of cationic lipid‑polymer hybrid nanoparticles (CLPNs) for co‑delivery of cisplatin (CDDP) and DNA (CDDP/DNA CLPNs) for the therapy of childhood head and neck cancers. CDDP/DNA CLPNs were prepared by the modified double emulsion solvent evaporation method with self‑assembly. CDDP‑loaded CLPNs (CDDP CLPNs), CDDP-loaded polymeric nanoparticles (PNPs) (CDDP PNPs), and DNA‑loaded Lipofectamine® 2000 (DNA LIPO) were also prepared for comparison. The results illustrated that the concentration of the cationic lipid has influence on the characteristics of CLPNs. In vitro anticancer effect, in vitro transfection efficiency, in vivo antitumor and gene delivery efficacy of CDDP/DNA CLPNs have advantages over other formulations tested. In conclusion, outstanding delivery ability of CLPNs for both CDDP and DNA could combine the therapeutic efficiency of both drug and gene for the treatment of pediatric rhabdomyosarcoma (RMS).

Topics: Animals; Antineoplastic Agents; Cell Survival; Child; Cisplatin; Combined Modality Therapy; Drug Carriers; Drug Delivery Systems; Flow Cytometry; Fluorescent Antibody Technique; Genetic Therapy; Head and Neck Neoplasms; Humans; Lipids; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Polymers; Transfection; Tumor Cells, Cultured

To investigate the immunological mechanism of mouse IL-2 gene therapy and the optimal lipid to DNA ratios of lipid-DNA complexed (lipoplexes) by using polycationic liposome-mediated Tumors were established in the transduction for head and neck squamous cell carcinoma (HNSCC).. floor of mouth in C3H/HeJ immunocompetent mice with SCCVII cell line. Lipoplexes with various lipid to DNA ratios (L:D) and naked DNA were transducted in vivo by direct intratumoral gene transfer and in vitro. The supernatants of SCCVII cell and tumour tissues were collected for IL-2 expression by enzyme-linked immunosorbent assay. Natural killer (NK) cell activity and cytotoxic T-lymphocyte (CTL) activity were also The optimal L:D ratio for IL-2 expression in vitro was not assayed by lactate dehydrogenase method.. consistent with that in vivo. By use of lipoplexes with L:D = 3:1, higher IL-2 expression of tumor tissues and greater activities of NK cell and CTL of murine spleen were noted in the treated group as compared with those A comparison of naked plasmid and lipid-complexed found in naked DNA and empty plasmid (EP).. DNA revealed that lipoplexes were more effective for intratumoral gene transfer to HNSCC. The results indicate that the formulation and dosage of polycationic L:D complexes play a key role in determining the level of intratumoral transgene expression.

Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Drug Carriers; Genetic Therapy; Head and Neck Neoplasms; Interleukin-2; Killer Cells, Natural; Lipids; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Polyamines; Polyelectrolytes; T-Lymphocytes, Cytotoxic; Transfection

The cisplatin induced enhancement of in situ lipofection was optimized by considering the factors that can increase the degree of sensitization. Two other anticancer drugs, mechlorethamine (nitrogen mustard) and taxol, enhanced CAT gene expression but the degree of sensitization was not as great as cisplatin. Besides human 2008 ovarian cancer cells we also found that human lung (A549) and head and neck cancer cells (SCC 25) were transiently sensitized by cisplatin. The transfectability of the two commercially available cationic liposomes, Lipofectin and LipofectAmine, was either weak or not consistent among tumors tested. In vivo transfection efficiency of 2008 cells was the highest at 1 microgram DNA per nmol or microgram liposome with all three cationic liposomes. In vitro transfection efficiency of 2008 cells at 1:1 (microgram of DNA:nmole of DC-chol/DOPE liposome) increased in a dose-dependent manner while at 1:10, an optimal ratio for in vitro lipofection, rapidly decreased with an increase in dose. This result indicated that there was a correlation between in vivo and in vitro lipofection at 1:1 ratio for delivering liposomal DNA. Most of the DNA injected into the tumor was concentrated in the tumor and in the skin above the tumor whether cisplatin was preinjected or liposomes were used as carriers.

Topics: Animals; Antineoplastic Agents; Bleomycin; Cation Exchange Resins; Chloramphenicol O-Acetyltransferase; Cholesterol; Cisplatin; DNA; Female; Head and Neck Neoplasms; Lipids; Liposomes; Lung Neoplasms; Mechlorethamine; Mice; Mice, SCID; Ovarian Neoplasms; Paclitaxel; Phosphatidylethanolamines; Transfection