In vitro transfection efficiencies of T-shaped spermine-based cationic lipids with identical and nonidentical tails under high serum conditions.

T-shaped spermine-based cationic lipids with identical and nonidentical hydrophobic tails having variable carbon lengths (from C10 to C18) were designed and synthesized. These lipids were characterized, and their structure-activity relationships were determined for DNA binding and transfection ability of these compounds when formulated as cationic liposomes. These liposomes were then applied as non-viral vectors to transfect HEK293T, HeLa, PC3, H460, HepG2, and Calu'3 cell lines with plasmid DNA encoding the green fluorescent protein. ST9, ST12 and ST13 with nonidentical tails could deliver DNA into HEK293T cells up to 60% under serum-free conditions. The lipid ST15 bearing nonidentical tails was found to be a potent gene transfer agent under 40% serum conditions in HEK293T and HeLa cells. Besides their low cytotoxicity, these lipoplexes also exhibited greater transfection efficiency than the commercially available transfection agent, Lipofectamine 3000.

Serum Compatible Spermine-Based Cationic Lipids with Nonidentical Hydrocarbon Tails Mediate High Transfection Efficiency.

Cationic lipids are widely used as nonviral synthetic vectors for gene delivery as a safer alternative to viral vectors. In this work, a library of L-shaped spermine-based cationic lipids with identical and nonidentical hydrophobic chains having variable carbon lengths (from C10 to C18) was designed and synthesized. These lipids were characterized and the structure-activity relationships of these compounds were determined for DNA binding and transfection ability when formulated as cationic liposomes. The liposomes were then used successfully for the transfection of HEK293T, HeLa, PC3, H460, HepG2, SH-SY5Y and Calu'3 cell lines. The transfection efficiency of lipids with nonidentical hydrocarbon chains was greater than the identical analogue. These reagents exhibited superior efficiency to the commercial reagent, Lipofectamine3000, under both serum-free and 10-40 % serum conditions in HEK293T, HeLa and H460 cell lines. The lipids were not toxic to the tested cell line. The results suggest that L-shaped spermine-based cationic lipids with nonidentical hydrocarbon tails could serve as efficient and safe nonviral vector gene carriers in further in vivo studies.

Dual-Targeted Therapy in HER2-Overexpressing Breast Cancer with Trastuzumab and Novel Cholesterol-Based Nioplexes Silencing Mcl-1.

The challenge in HER2-overexpressing breast cancer therapy lies in creating an effective target therapy to overcome treatment resistance. Monoclonal antibodies and target gene silencing by siRNA are two potential strategies that have been widely developed for treating HER2-positive breast cancer. The siRNA delivery system is a crucial factor that influences siRNA therapy's success. In this study, lipid-based nanoparticles (cationic niosomes) composed of different cholesterol-based cationic lipids were formulated and characterized for delivering siRNA into HER2-overexpressing breast cancer cells. Niosomes containing a trimethylammonium headgroup showed the highest siRNA delivery efficiency with low toxicity. The myeloid cell leukemia-1 (Mcl-1) siRNA nioplex treatment significantly decreased mRNA expression and breast cancer cell growth. Dual-targeted therapy, consisting of treatment with an Mcl-1 siRNA nioplex and trastuzumab (TZ) solution, noticeably promoted cell-growth inhibition and apoptosis. The synergistic effect of dual therapy was also demonstrated by computer modeling software (CompuSyn version 1.0). These findings suggest that the developed cationic niosomes were effective nanocarriers for siRNA delivery in breast cancer cells. Furthermore, the Mcl-1 nioplex/TZ dual treatment establishes a synergistic outcome that may have the potential to treat HER2-overexpressing breast cancer.

Morindaquinone, a new bianthraquinone from Morinda coreia roots.

Phytochemical investigation of the roots of Morinda coreia led to the isolation of one new bianthraquinone, morindaquinone (1), together with 12 known compounds, soranjidiol (2), rubiadin-1-methyl ether (3), 2-methoxy-1,3,6-trihydroxyanthraquinone (4), 1-hydroxy-2-methylanthraquinone (5), tectoquinone (6), nordamnacanthal (7), damnacanthal (8), 2-formylanthraquinone (9), 3-hydroxy-2-hydroxymethylanthraquinone (10), lucidin-ω-methyl ether (11), scopoletin (12) and (+)-mellein (13). The structures of these compounds were determined on the basis of extensive spectroscopic analyses, as well as by comparison with literature reports. Compound 1 was the first example of bianthraquinone found in the genus Morinda, whereas compound 13 was firstly isolated from this genus. Among them, compounds 2, 7, 8 and 10 exhibited moderate to weak cytotoxicity against human cervical (HeLa), human colon (HT 29) and human breast (MCF-7) cell lines, while compounds 6 and 9 - 11 showed weak anti-acetylcholinesterase activity.

The effect of polar headgroups and spacer length on the DNA transfection of cholesterol-based cationic lipids.

This article is related to the effects of the headgroups and spacer length of cationic lipids on transfection efficiency. To develop highly potent cationic lipids, a series of divalent lysine-diamine conjugated cholesterol-based cationic lipids with three different headgroups (ammonium, trimethyl ammonium, and guanidinium) were synthesized. The newly synthesized cationic lipids (1-6)A formed cationic liposomes in the presence and absence of a zwitterionic helper lipid, DOPE (dioleoylphosphatidylethanolamine). A gel retardation assay showed that most of the prepared lipoplexes could retard DNA migration in the presence of DOPE. We attempted to modify the diverse cationic headgroups to improve the transfection efficiency. However, the lysine-1,3-diaminopropane-conjugated cholesterol-based lipid 4A, having divalent ammonium of unmodified lysine headgroup, exhibited high relative transfection efficiency in HEK293. When the transfection efficiency of 4A was formulated with DOPE (1 : 1 weight ratio), it produced the same range in comparison with that of a commercially available transfection agent, Lipofectamine™ 2000 (L2k). The lipid 4A was studied to optimize the conditions with respect to the lipid/DOPE and DNA/lipid ratios and the amount of DNA. The transfection efficiency of the highly potent lipid 4A was also studied to determine the transfection efficiency of HeLa, PC3, and HC-04 cell lines. This lipid also protected the DNA from a serum and had low toxicity. Lipoplexes 4A with DOPE had the particle size of around 300-600 nm and the zeta potential of around 0-45 mV. In summary, cationic liposomes 4A demonstrated a high performance as DNA carriers.