Drug delivery systems for cancer chemotherapy are employed to improve the effectiveness and decrease the side-effects of highly toxic drugs. Most chemotherapy agents have indiscriminate cytotoxicity that affects normal, as well as cancer cells. To overcome these problems, new more efficient nanosystems for drug delivery are increasingly being investigated. Polyamidoamine (PAMAM) dendrimers are an example of a versatile and reproducible type of nanocarrier that can be loaded with drugs, and modified by attaching target-specific ligands that recognize receptors that are over-expressed on cancer cells. PAMAM dendrimers with a high density of cationic charges display electrostatic interactions with nucleic acids (DNA, siRNA, miRNA, etc.), creating dendriplexes that can preserve the nucleic acids from degradation. Dendrimers are prepared by conducting several successive “generations” of synthetic reactions so their size can be easily controlled and they have good uniformity. Dendrimers are particularly well-suited to co-delivery applications (simultaneous delivery of drugs and/or genes). In the current review, we discuss dendrimer-based targeted delivery of drugs/genes and co-delivery systems mainly for cancer therapy.
The use of liposomes as drug carriers improves the therapeutic efficacy of anticancer drugs, while at the same time reducing side effects. Hyaluronic acid (HA) is recognized by the CD44 receptor, which is overexpressed in many cancer cells. In this study, we developed HA-modified liposomes encapsulating 5-fluorouracil (5-FU) and tested them against a CD44 expressing colorectal cell line (HT29) and a non-CD44 expressing hepatoma cell line. The average size of 5-FU-lipo and 5-FU-lipo-HA nanoparticles were 112 ± 28 and 144 ± 77 nm, respectively. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay showed selective cancer cell death depending on the CD44 expression in a time-dependent manner. Apoptosis assays and cell-cycle analysis indicated that G0/G1 arrest occurred. The colony formation study revealed that cells treated with 5-FU-lipo and 5-FU-lipo-HA had reduced colony formation. Quantitative reverse-transcription polymerase chain reaction study showed that the oncogenic messenger RNA and microRNA levels were significantly reduced in the 5-FU-lipo-HA-treated group, while tumor suppressors were increased in that group. We suggest that optimal targeted delivery and release of 5-FU into colorectal cancer cells, renders them susceptible to apoptosis, cell-cycle arrest, and decreased colony formation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.