Low generation polyamidoamine dendrimers (PAMAM) and biotin-PAMAM conjugate – the detailed structural studies by 1H and 13C nuclear magnetic resonance spectroscopy

Abstract

Introduction. The concept of targeted drug delivery is nowadays based on nanoparticle transporters. Such drug delivery systems for cancer cells should follow the requirements like: efficient drug release, selective binding and internalization to cancer cells. The anticancer drug selectivity can be achieved by attachment of cancer cell-recognizing molecules, like biotin. Among nanosized carriers the PAMAM dendrimers are tested intensely, especially they can be modified by covalent attachment of prodrug molecules and biotin as targeting molecule. Aim. We aimed at construction and characterization of a conjugate formed between PAMAM and biotin (Biot). The nuclear magnetic resonances is powerful tool to determine both the structure and stoichiometry of the conjugate. Material and methods. PAMAM G0 has been synthesized and functionalized with biotin by reaction with N-hydroxysuccinimide ester of biotin to obtain G0 double-substituted with biotin. All the compound were thoroughly characterized by the NMR spectroscopy. Results. The conjugate of PAMAM G0 dendrimer with two amide-bonded biotin molecules was obtained and fully characterized by NMR spectroscopy. Conclusion. N-hydroxysuccinimide ester of biotin spontaneously reacts with PAMAM G0 to obtain the conjugate of 2:1 biotin: G0 stoichiometry. The latter was designed as a targeting molecule in formation of megameric multidrug delivery system.

Biotin Transport-Targeting Polysaccharide-Modified PAMAM G3 Dendrimer as System Delivering α-Mangostin into Cancer Cells and C. elegans Worms

“…Afterwards, the solvent was removed by vacuum rotary evaporation and dried under high vacuum overnight. The product was identified by 1 H NMR spectroscopy as G3 substituted with average two residues of amide-bonded biotin G3 2B , as described before [ 24 , 25 ]. The isolated yield of the product was 47% (501 mg; 68 μmoles; MW calc = 7362 g mol −1 ).…”

Synthesis and characterization of Fulvestrant and Paclitaxel conjugates with polyamidoamine dendrimer fourth generation

“…In our previous study we have applied the NMR spectroscopy to characterize the low molecular weight PAMAM G3 conjugates with covalently attached biotin. 25 Later we used PAMAM G3 macromolecular carrier to construct the drug delivery system (DDS) for anticancer drugs: Lapatinib (L) and Fulvestrant (F) and tested those conjugates against three breast cancer cell lines in vitro. 7 We have found that G3-L-F binary conjugate promoted apoptosis in chemotherapy-induced senescent breast cancer cells with different receptor status.…”