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Tumor Discovery                                         Targeted drug delivery systems for the treatment of tumors



            in the pDNA backbone) of 20. Furthermore, cell viability   linked polyethylenimine and PEG to develop GE11-tethered
            was found to decrease in a dose-dependent manner. The   polyplexes and evaluated their transfection efficiency in
            results revealed that fabricated polyplexes (composed of   EGFR-overexpressed tumor cells. The formulated polyplexes
            polycationic phosphorous dendrimers and plasmid) had   demonstrated efficient gene condensing capacity, improved
            reduced positive charge in the system, resulting in minimal   transfection efficiency, and specific targeting capabilities .
                                                                                                           [81]
            cytotoxicity. These outcomes suggested that the fabricated   Polyplexes are generally designed for receptor-mediated
            phosphorus  dendrimers  hold  promise  as  an  effective   gene delivery through systemic routes, facilitating efficient
            carrier system for gene delivery in cancer treatment .  internalization due to their augmented transfection
                                                     [67]
                                                               efficiency. In this context, Taschauer  et al. evaluated the
            (d) Polyplexes
                                                               significance of the overexpression of CD49f in both benign
            These polymeric nanocarriers are formulated by     and malignant tumors . CD49f molecules are associated
                                                                                 [82]
            conjugating siRNA/DNA or genes via electrostatic   with the phosphatidylinositol 3-kinase and the serine/
            interactions between cationic polymers and anionic   threonine  protein  kinase (Akt  signaling  pathway), which
            nucleic acid components. These systems serve the dual   play a crucial role in the regulation and development of bone
            proposes of protecting sensitive genes from enzyme   mesenchymal stem cells and contribute to tumor metastasis
            degradation and facilitating controlled release at the tumor   in  solid  cancers  such  as  hemangioma,  breast  cancer,
            site. Polycationic polyplexes show great promise as a drug   prostate  cancer, and gastric cancer.  A  nanodimensional
            delivery approach for the specific delivery of anticancer   molecular conjugate (200  nm) consisting of the CD49f
            agents due to their ability to enhance transfection   peptide (CYESIKVAVS) and linear polyethyleneimine
            efficiency. DNA polyplexes (polymeric-based) and DNA   (LPEI) was synthesized for the purpose of targeting
            lipoplexes (lipid-based) are systemic gene delivery systems   breast tumor lesions. The fabricated polyplexes could be
            necessary for cases of tumor metastases, where cancerous   aerosolized without particle aggregation. When delivered
            cells spread throughout the organism. Polyethyleneimine   through intratracheal aerosolization, the system was well-
            polyplexes, functionalized with PEG, have been developed   tolerated and demonstrated measurable transgene efficacy.
            and conjugated with transferrin or epidermal growth   Hattori compiled various cationic and anionic polyplexes
            factor to facilitate effective DNA (or gene) transfer within   with genes to enable their delivery to tumor-targeted sites
            tumor cells. This modification masks the surface charge   without aggregation with blood components . Surface
                                                                                                    [83]
            of polyplexes to prevent interactions with systemically   modification of cationic polyplexes with anionic polymers
            present circulatory components, including erythrocytes,   led to the development of a stable drug delivery approach
            plasma, and the reticuloendothelial system .  Table 5   that effectively delivered pDNA and siRNA to the target
                                                [80]
            enlists surface-modified cationic and anionic polyplexes   site .
                                                                  [84]
            designed to efficiently deliver nucleic acid in tumors.
              Lee et al. explored the successful delivery of branched   4.2.2. Lipid carriers
            peptide (GE11) for cancer cells overexpressing EGFR. They   Lipid-based nanosystems are extensively utilized for
            investigated the use of low molecular weight disulfide cross-  targeting and regulating the tumor microenvironment

            Table 5. Surface-modified polyplexes and their conjugates for nucleic acid delivery in tumor management

            Polyplexes                       Nucleic acid           Conjugate                       References
            Cationic polymers
             Lipofectamine 2000               Plasmid DNA           Hyaluronic acid (HA)               [84]
             Chitosan                         Plasmid DNA           Hyaluronic acid                    [85]
             Polyamidoamine                   Plasmid DNA           Hyaluronic acid                    [86]
             Protamine                        Antisense DNA         HA-antisense DNA                   [87]
             Dendrigraft poly-L-lysine        Plasmid DNA           Chondroitin sulfate                [88]
            Anionic polymers
             Poly-ᵞ-glutamic acid             Plasmid DNA           Chitosan                           [89]
             Poly-ᵞ-glutamic acid             siRNA                 Dendrigraft poly-L-lysine          [90]
             Heparin                          Plasmid DNA           Cationic glycopolymer (Tr4)        [91]
             Poly-ᵞ-glutamic acid             siRNA                 Polyethylenimine                   [92]


            Volume 2 Issue 3 (2023)                         11                         https://doi.org/10.36922/td.1356
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