RESUMO
An ideal nano drug delivery agent must be potent enough to carry high dose of therapeutics and competent enough in targeting specific cell of interest, having adequate optimized physiochemical properties and biocompatibility. Carrying differentially polar therapeutics simultaneously will make them superior in their class. However, it is of enormous challenge to the researchers to find such a unique nanocarrier and to engineer all of the above-mentioned features into it. In this manuscript, we have shown for the first time that apoferritin (Apf) can carry and deliver high dose of doxorubicin (Dox), docetaxel (Doc), and combination of both Dox and Doc specifically into the cancer cell and enhances killing compared to free drug without any functionalization or property modulation. In addition, we have shown that Apf alone is noncytotoxic in nature and interacts with intracellular tubulin/microtubule. Drug loaded Apf specifically bound and consequently internalized into the human breast cancer cell line (MCF7) and human cervical cancer cell line (HeLa) through receptor mediated endocytosis process and releases either single or combination of drugs in the endosome. We have also checked the binding efficacy of both drugs using molecular docking. Further, using fluorescence microscopy, we have shown that Apf can deliver combination of drugs inside cancer cells and the drugs exerts their effect thereof. Finally, we have studied the efficacy of Apf complexes with individual drugs and in combination compared to free drugs in a tumor mimicking 3D multicellular spheroid model of HeLa cell.
Assuntos
Apoferritinas/química , Antineoplásicos , Linhagem Celular Tumoral , Núcleo Celular , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Células HeLa , Humanos , Microtúbulos , Simulação de Acoplamento Molecular , NanoestruturasRESUMO
Enzyme modifiable, hollow self-assembled structures offer an excellent scope for multiantennary delivery vectors. Herein, we report synthesis and applications of bis-galactose lysine based supramolecular ensembles, which possess surface galactose moieties amenable to enzymatic modifications. This post-synthetic modification generates reactive aldehyde groups, which could possibly serve as dynamic anchors for crosslinking and cell adhesion.
Assuntos
Galactose/metabolismo , Hepatócitos/metabolismo , Aminas/química , Adesão Celular , Galactose/química , Galactose Oxidase/metabolismo , Ouro/química , Células Hep G2 , Hepatócitos/citologia , Humanos , Nanopartículas Metálicas/química , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Oxidiazóis/químicaRESUMO
A series of novel 5-substituted-1-(arylmethyl/alkylmethyl)-1H-indole-2,3-dione-3-(N-hydroxy/methoxy thiosemicarbazone) analogues were synthesized and evaluated for their anti-HIV activity and anti-tubercular activity in both log phase and starved cultures. The compound 2-(1-{[4-(4-chlorophenyl)tetrahydropyrazin-1(2H)-yl]methyl}-5-methyl-2-oxo-1,2-dihydro-3H-indol-3-yliden)-N-(methyloxy)hydrazine-1-carbothioamide (B21) displayed promising activity against the replication of HIV-1 cells (EC(50) 1.69 µM). In anti-mycobacterial screening B21 proved effective in inhibiting the growth of both log phase (MIC 3.30 µM) and starved (MIC 12.11 µM) MTB cultures. Isocitrate lyase enzyme having momentous implication in persistent TB was shown to be inhibited by 1-cyclopropyl-6-fluoro-7-[4-{[5-methyl-3-((Z)-2-{[(methyloxy)amino]carbothioyl}hydrazono)-2-oxo-1H-indol-1(2H)-yl]methyl}tetrahydropyrazin-1(2H)-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (B30) with 63.44% inhibition at 10 mM.