RESUMO
Rapid release and clearance of antitumor drugs in vivo are the main factors used to evade the effectiveness of chemotherapeutics. Targeted delivery and controlled release of drugs are the most pressing dilemmas in cancer therapy. Herein we report the design and fabrication of multifunctional mesoporous silica nanoparticles coated with poly(N-isopropylacrylamide)-co-acrylic acid and calcium phosphate (MSCNs) with pH-triggered chemotherapeutic release and dual-targeting functions. By decorating the nanoparticle surface with a transferrin (Tf)/RGD ligand, these nanoparticles are capable of not only recognizing the intrinsic pH difference between tumor and normal tissues, but also targeting the lesion location. It was shown that Tf/RGD-MSCNs delivered the anti-tumor drug doxorubicin more efficiently into lysosomes and the resulting DOX-loaded nanoparticles (DOX-Tf/RGD-MSCNs) showed a stronger inhibitory effect towards tumor cell growth than free DOX and DOX delivered by unmodified MSNs. Moreover, the nanoparticles are more biocompatible than uncoated mesoporous silica nanoparticles. All these results indicate that Tf/RGD-MSCNs have great potential as a novel drug carrier in therapeutic applications against cancers.
Assuntos
Antineoplásicos/farmacologia , Fosfatos de Cálcio/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Dióxido de Silício/química , Acrilamidas/química , Antineoplásicos/química , Doxorrubicina/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana , Humanos , Concentração de Íons de Hidrogênio , Lisossomos/metabolismo , Polímeros/química , PorosidadeRESUMO
Vitamin E derivatives possess many essential features for drug-delivery applications, such as biocompatibility, stability, improvement of water solubility of hydrophobic compounds, anticancer activity, and the ability to overcome multidrug resistance (MDR). Herein, vitamin E derivatives are used to overcome MDR through a combined P-glycoprotein (P-gp) inhibition and mitochondrial impairment strategy. A novel nanomicellar drug-delivery system as a carrier for doxorubicin (DOX) was developed, in which d-α-tocopheryl polyethylene glycol 1000 succinate was used as a P-gp inhibitor, α-tocopheryl succinate was introduced as a mitochondrial disrupting agent, and d-α-tocopheryl polyethylene glycol 2000 succinate was used as the main building block of micelles. The optimal ratio between the components of the nanocarrier was determined. The resultant DOX-loaded mixed micelles exhibited a suitable size of 52.08 nm, high drug-loading encapsulation efficiency (>98%), high stability, and pH-dependent drug release. In vitro experiments demonstrated a significantly increased cytotoxic activity of DOX-loaded mixed micelles against resistant MCF-7/Adr cells (45-fold higher than DOX after 48 h of treatment). In vivo studies revealed superior antitumor efficiency with less cardio- and hepatotoxicities of DOX-loaded micelles compared with that of free DOX. These results highlight that the developed DOX-loaded mixed micelles have a promising potential to overcome MDR in chemotherapy for clinical usage.
Assuntos
Nanoestruturas , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Linhagem Celular Tumoral , Doxorrubicina , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Micelas , Polietilenoglicóis , Vitamina ERESUMO
Thanks to developments in the field of nanotechnology over the past decades, more and more biosafe nanoscale materials have become available for use as pharmaceutical adjuvants in medical research. Nanomaterials possess unique properties which could be employed to develop drug carriers with longer circulation time, higher loading capacity, better stability in physiological conditions, controlled drug release, and targeted drug delivery. In this review article, we will review recent progress in the application of representative organic, inorganic and hybrid biosafe nanoscale materials in pharmaceutical research, especially focusing on nanomaterial-based novel drug delivery systems. In addition, we briefly discuss the advantages and notable functions that make these nanomaterials suitable for the design of new medicines; the biosafety of each material discussed in this article is also highlighted to provide a comprehensive understanding of their adjuvant attributes.
Assuntos
Adjuvantes Farmacêuticos/farmacologia , Materiais Biocompatíveis/química , Nanoestruturas/química , Preparações Farmacêuticas/química , Animais , Humanos , Compostos Inorgânicos/química , Nanoestruturas/ultraestrutura , Compostos Orgânicos/químicaRESUMO
The fluorescence of tetraphenylethylene (TPE), an archetypal luminogen, is induced by restriction of intramolecular rotation (RIR). TPE was grafted with palmitic acid (PA) onto a hydrophilic peptide to yield a cell membrane tracker named TR4. TR4 was incorporated into liposomes, where it showed significant RIR characteristics. When cells were incubated with TR4, cytoplasmic membranes were specifically labeled. TR4 shows excellent photostability and low cytotoxicity.
Assuntos
Membrana Celular/química , Ácido Palmítico/química , Cálcio/química , Etilenos/química , Fluorescência , Lipossomos/química , Peptídeos/químicaRESUMO
Multifunctional nanoparticles as theranostic tools hold great potential for its unique and efficient way to visualize the process of disease treatment. However, the toxicity of conventional fluorescent labels and difficulty of functionalization limit their widespread use. Recently, a number of amino-rich polymers have demonstrated high luminescent fluorescence but rarely showed potential for in vivo imaging due to their blue fluorescence. Here, a general route has been found to construct polymer-based multifunctional nanoparticles for combined imaging and drug delivering. The weak fluorescent polyethyleneimine (PEI) has been conjugated with hydrophobic polylactide as the amphiphilic PEI for construction of nanoparticles which showed bright and multicolor fluorescence with high drug loading capacity. The paclitaxel-loaded nanoparticles showed significant therapy effect in contrast to the free paclitaxel. Meanwhile, fluorescence imaging of the nanoparticles showed accumulation around tumor. These results demonstrate a new type of polymer-based multifunctional nanoparticles for imaging-guided drug delivery.