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Nanotechnology has significantly impacted medicine by improving diagnostics and therapeutics. By modifying materials at the nanoscale, we can impart unique and desirable characteristics to the nanoparticles (NPs), which are not present in their bulk counterparts. Gold NPs (AuNPs) have emerged as potential vehicles for drug delivery due to their favourable attributes, such as low toxicity, high surface area, high loading capacity, biocompatibility, ease of synthesis, and surface modification. Although anticancer drugs are effective, they are rapidly metabolized in the body after administration, reducing their effectiveness in addition to inducing severe side effects. Hence, this study aimed to address the need for a safe and effective drug delivery system that will ensure controlled drug release to the desired tumour site. In this study, AuNPs were chemically synthesized, conjugated to the targeting ligand, transferrin and loaded with a dual-drug formulation of doxorubicin (DOX) and 5-fluorouracil (5-FU) encapsulated within a chitosan (CS) matrix. Characterization revealed that the AuNPs were spherical in shape, with a good size distribution in the range of 54.9 ± 7.5 nm. The encapsulation efficiency was calculated to be 72.63 % for 5-FU and 74.81 % for DOX, which implied a higher therapeutic load for delivery to the cancer cells. Drug release studies revealed a controlled drug release profile, with 5-FU encapsulated CS-Tf-AuNPs and DOX encapsulated CS-Tf-AuNPs releasing 82.31 % and 80.86 % of 5-FU and DOX, respectively, over 72 h, while the dual drug encapsulated CS-Tf-AuNPs generated a release of 77.33 % 5-FU and 75.60 % DOX over the same period. In vitrocytotoxicity in the human cancer cell lines, HeLa (cervical carcinoma), MCF-7 (breast adenocarcinoma), and the non-cancer HEK293 (embryonic kidney) revealed a specificity of the nanocomplexes to the cancer cells, with little or no significant toxicity observed in the non-cancer cells. The transferrin-targeted nanocomplexes exhibited greater anticancer activity than their non-targeted counterparts. These results highlight the potential of these targeted dual-drug AuNP nanocomplexes in providing safe and efficient delivery of anticancer drugs with reduced side effects in vitro.

Interest in hepatocyte-directed liposomal gene delivery is driven, in part, by the lack of effective treatment for several liver-associated disorders. To impart a hepatocyte targeting capability on DNA-lipoplexes, and to promote early release of cargo DNA from endosomes, novel glycosylated and imidazolylated cholesteryl derivatives have been synthesized and evaluated in vitro. Thus cholesteryl-3β-N-[(lactobionyl) amino] carbamate (Chol-LAC) and cholesteryl-3β-N- [(urocanyl) amino] carbamate (Chol-UAC) have been formulated with the cytofectin cholesteryl-3β-[(N’,N’- dimethylaminopropyl) carbamate (Chol-T) and the neutral co-lipid dioleoylphosphatidyl ethanolamine (DOPE). Liposomes, which displayed a buffering capability at endosomal pH, effectively bound DNA at a N/P ratio of 0.8:1 and offered partial protection against serum nuclease digestion. The MTT cell viability assay showed that lipoplexes were well tolerated by human hepatoma cells (HepG2), which were efficiently transfected almost exclusively by asialoglycoprotein receptor (ASGP-R)–mediation, as demonstrated in competition assays. In the ASGP-R-negative human kidney cell line (HEK293) transfection levels were considerably lower (P < 0.001). Therefore the combination of Chol-LAC and Chol- UAC in cationic liposomal formulations may provide a platform for the development of useful hepatotropic gene delivery systems.