Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector–p53

Abstract

Lung cancer still remains to be challenged by novel treatment modalities. Novel locally targeted routes of administration are a methodology to enhance treatment and reduce side effects. Intratumoral gene therapy is a method for local treatment and could be used either in early-stage lung cancer before surgery or at advanced stages as palliative care. Novel non-viral vectors are also in demand for efficient gene transfection to target local cancer tissue and at the same time protect the normal tissue. In the current study, C57BL/6 mice were divided into three groups: (a) control, (b) intravenous and (c) intatumoral gene therapy. The novel 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector (Ryujyu Science Corporation) was conjugated with plasmid pSicop53 from the company Addgene for the first time. The aim of the study was to evaluate the safety and efficacy of targeted gene therapy in a Lewis lung cancer model. Indeed, although the pharmacokinetics of the different administration modalities differs, the intratumoral administration presented increased survival and decreased distant metastasis. Intratumoral gene therapy could be considered as an efficient local therapy for lung cancer.

Use and Safety of Intratumoral Application of European Mistletoe (Viscum album L) Preparations in Oncology

“…[2][3][4][5][6][7][8][9] Potential advantages of IT delivery of anticancer drugs include better anticancer effectiveness through achievement of high concentrations of anticancer agents within the tumor microenvironment and reduced systemic adverse drug reactions (ADRs) and drug resistance. 5,[10][11][12] In general, single-agent efficacy has been less than satisfying to date; however, promising results have been achieved using IT-administered targeted therapies, combined with conventional chemotherapy or radiation. 10,[13][14][15][16][17] A major challenge of cancer therapy is immune resistance orchestrated by the tumor microenvironment, which promotes tumor survival.…”

Anticancer efficacy of a supramolecular complex of a 2-diethylaminoethyl–dextran–MMA graft copolymer and paclitaxel used as an artificial enzyme

“…It was reported recently that the administration of DDMC as an aerosol [25] and the use of DDMC/p53 in intratumoral gene therapy [26] were effective. DDMC is very suitable for experiments using targeted siRNA or miRNA transfection in vivo.…”

Medicinal facilities to B16F10 melanoma cells for distant metastasis control with a supramolecular complex by DEAE-dextran-MMA copolymer/paclitaxel

“…The resulting DDMC consists of "hairy" nanoparticles having a hydrophilic-hydrophobic microseparated domain with an amphiphilic domain (DEAE-dextran) and a hydrophobic domain (PMMA) that form a polymer micelle [15]. It has been reported that DDMC is superior to other transfection agents with safety efficacy by autoclaved as a non-viral carrier for gene introduction [16][17][18][19][20][21][22][23][24]. On the other hand, the paclitaxel is well known as a strong anti-cancer drug to introduce cancer cells to apoptosis in stabilization of tubulin (i.e., tubulin polymerization) [14,[25][26][27].…”