RESUMEN
The single crystals of two novel mixed-ligand copper(ii)-based complexes were obtained and characterized. These complexes can remarkably induce apoptosis, inhibit proliferation, suppress migration and metastasis, and inhibit angiogenesis to inhibit the growth of cervical cancer by down-regulating the expressions of the important proteins FAK, Akt and Erk1/2 or their phosphorylated proteins p-FAK, p-Akt, and p-Erk1/2 downstream of the VEGF/VEGFR2 signaling pathway.
Asunto(s)
Complejos de Coordinación/síntesis química , Complejos de Coordinación/farmacología , Cobre/química , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Técnicas de Química Sintética , Complejos de Coordinación/química , Humanos , Ligandos , Modelos Moleculares , Conformación MolecularRESUMEN
Drug-conjugated gold nanoparticles (GNPs), which are generally constructed with many molecules of thiol-terminated polyethylene glycol (PEG)-drug decorated on their surfaces via a thiol-Au covalent bond, are promising and efficient nanoprodrugs. However, because of the exposure of the hydrophobic drug molecules on the surface of the conjugate, in vivo stability, opsonization, and subsequent inefficient therapy become the main issues of this system. To solve these problems without complicating the structures of gold conjugates, herein we propose a method to change the relative position of PEG and the drug. A novel gold conjugate (GNP-NHNâDox-mPEG) with doxorubicin (Dox) shielded by PEGylation on the surface of GNPs is designed. It demonstrates improved solubility, stability, and dispersion and achieves a two-step stimulus-responsive drug release in response to an acidic environment in lysosomes and then esterase in the cytoplasm. This unique manner of release enables the cytoplasm to act as a reservoir for sustained drug delivery into the nucleus to improve antitumor efficacy in vivo. The intratumoral drug concentrations of the conjugate reach 14.4 ± 1.4 µg/g at 8 h, a two-fold increase in the drug concentration compared with that of the doxorubicin hydrochloride group. This molecular design and regulation approach is facile but important in modulating the in vivo performance of nanovehicles and demonstrates its vital potential in developing effective nanoparticle-based drug delivery agents.
Asunto(s)
Nanopartículas del Metal , Línea Celular Tumoral , Doxorrubicina , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Oro , Humanos , PolietilenglicolesRESUMEN
Gold nanoparticles (AuNPs) have demonstrated increasingly wide applications in drug delivery due to their unique physicochemical and optical properties as well as low toxicity. Compared to the organic nanocarriers for therapeutic agents, AuNPs have shown superior performance as drug delivery vectors, including the inert nature, well-developed synthesis strategies, tunable size, and flexible and easy surface modification with various chemical and biological molecules. In this review, we emphasize on the applications of AuNPs in the aspect of improving pharmaceutical property and therapeutic efficacy of drugs, especially those covalently and noncovalently connected to the surface of AuNPs. Acting as a solid core to link drugs and their derivatives, AuNPs provide the nano-prodrug system with compressed size, high loading efficiency, three-dimension structure, and enhanced cellular uptake capability. With the intensive and systematical investigation of the drug-connected AuNPs, several important issues will become the hot but emergent topics for future research in this field, such as the toxicity in live human subjects, ultimate destination, and possible pathways and mechanisms for their absorption, circulation, distribution, metabolism, and excretion.
