Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3β-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d50=138 nm for A-loaded HAp/ChOSL and d50=223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.

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Conjugates of ferrocene with steroidal estrogens as selective antiproliferative agents against hormone‐dependent breast cancer cells are believed to be limited by the inherent estrogenicity of the conjugates. Motivated by a significant cytotoxicity of the ester of ferrocenecarboxylic acid and the phenolic group of estradiol toward such a cell line, we decided to explore other a‐ring‐tethered ferrocene–estra‐1,3,5(10)‐triene conjugates; in this study, ferrocenylmethylation of estradiol and estrone with (ferrocenylmethyl)trimethylammonium iodide in the presence of potassium carbonate yielded five new compounds (1–5). In dimethylformamide, only O‐alkylated products formed (1 and 3), while a mixture of O‐ and C‐alkylated products was obtained when methanol was used (2, 4, and 5 in addition to 1 and 3). All compounds were characterized using 1D and 2D NMR, IR, UV–Vis, and high‐resolution mass spectrometry. Two of the conjugates, a 3‐O‐ and a 4‐C‐alkylated derivative of estrone (3 and 4, respectively), were also analyzed using single‐crystal X‐ray diffraction. A cyclic voltammetric investigation of the electrochemical properties of 1–5 was performed. While some of the compounds were shown to have a slight‐to‐moderate antiproliferative activity against at least one of the six tested human tumor cell lines and were nontoxic to (the noncancerous) fetal human fibroblasts, compound 2 (4‐(ferrocenylmethyl)estra‐1,3,5(10)‐triene‐3,17β‐diol) with an IC50 value of 0.34 μM was found to be more active against the hormone‐dependent breast cancer cell line MCF‐7 than doxorubicin. These results suggest that a‐ring substitution of steroidal estrogens is a plausible strategy for preparing other ferrocene–steroid conjugates acting against tumor cells.

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