ABSTRACT
Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies. Heat shock protein 90 (Hsp90) as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and resistance. Targeting Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and resistance. In this study, a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX, and a COA-modified 4-arm PEG polymer (4PSC) was synthesized. COA, an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression, was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory activity. Our results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic toxicity. By blocking the Hsp90 signaling pathway, 4PSC significantly enhanced the antitumor effect of PTX, inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in vitro. Remarkable results were further confirmed in vivo with two preclinical tumor models. These findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.
ABSTRACT
Although high-efficiency targeted delivery is investigated for years, the efficiency of tumor targeting seems still a hard core to smash. To overcome this problem, we design a three-step delivery strategy based on streptavidin-biotin interaction with the help of c(RGDfK), magnetic fields and lasers. The ultrasmall superparamagnetic iron oxide nanoparticles (USIONPs) modified with c(RGDfK) and biotin are delivered at step 1, followed by streptavidin and the doxorubicin (Dox) loaded nanosystems conjugated with biotin at steps 2 and 3, respectively. The delivery systems were proved to be efficient on A549 cells. The co-localization of signal for each step revealed the targeting mechanism. The external magnetic field could further amplify the endocytosis of USPIONs based on c(RGDfK), and magnify the uptake distinctions among different test groups. Based on photoacoustic imaging, laser-heating treatment could enhance the permeability of tumor venous blood vessels and change the insufficient blood flow in cancer. Then, it was noticed that only three-step delivery with laser-heating and magnetic fields realized the highest tumor distribution of nanosystem. Finally, the magnetism/laser-auxiliary cascaded delivery exhibited the best antitumor efficacy. Generally, this study demonstrated the necessity of combining physical, biological and chemical means of targeting.
ABSTRACT
Until now, great progress has been made in anti-tumor therapy. A series of novel anti-tumor drugs, such as molecular targeted drugs and monoclonal antibodies, have been emerging one after another, which have benefited a great number of tumor patients in different degrees. However, there are still many dilemmas in clinical anti-tumor therapy at present, for instance, obvious side effects, tumor resistance and so on. In recent years, the nano drug delivery system with mesoporous silica as the carrier has overcome many flaws of traditional anti-tumor treatment to a certain extent, especially the mesoporous silica nanosystem for controlling reactive oxygen species generation which has excellent tumor targeting property and biocompatibility, and minimal injury effects on normal tissue cells. So it has been regarded as one of the most promising agents in clinical application by playing significant anti-tumor roles through multiple approaches. This paper reviews this kind of potent nanosystem and its application to anti-tumor therapy.
ABSTRACT
Extracts from leaves of C. sylvestris have cytotoxic effect in different tumor cell lines, possibly due to clerodane type diterpenes (casearins). On the other hand, there are few studies related to the antitumor activity of the essential oils from this species. This work evaluated for the first time the cytotoxicity effects of the pure essential oil and its nanoemulsion against A549 tumor cell line (human lung carcinoma). The essential oil was obtained from fresh leaves by hydrodistillation in a Clevenger-type apparatus and analyzed by GC/MS and GC/FID. Cytotoxicity evaluation was performed using the WST-1 test. The chemical analysis of the essential oil revealed a volatile fraction composed mainly of non-oxygenated sesquiterpenes (72.1%). The essential oil and its nanoemulsion exhibited cytotoxic activity against A549 tumor cells with EC50 of 4.0 µg/mL and EC50 of 1.0 µg/mL, respectively. Both samples displayed a dose dependent pattern (r = -0.79, p = 0.03) as determined by linear regression test.
Los extractos de las hojas de Casearia sylvestris tienen efectos citotoÌxicos en diferentes liÌneas celulares tumorales, posiblemente debido a los diterpenos tipo clerodane (casearinas). Por otra parte, hay muy pocos estudios relacionados con la actividad antitumoral del aceite esencial de estas especies. Este trabajo evaluÌa por primera vez el efecto citotoÌxico del aceite esencial puro y su nanoemulsioÌn contra la liÌnea de ceÌlulas tumorales A549 (carcinoma humano de pulmoÌn). El aceite esencial fue obtenido de hojas frescas por hidrodestilacioÌn en un aparato tipo Clevenger y analizado por GC/MS y GC/FID. La evaluacioÌn de citotoxicidad fue realizada usando la prueba WST-1. El anaÌlisis quiÌmico del aceite esencial reveloÌ una fraccioÌn volaÌtil compuesta principalmente por sesquiterpenos no oxigenados (72,1%). El aceite esencial y su nanoemulsioÌnexhibioÌ actividad citotoÌxica contra las ceÌlulas tumorales A549 con una EC50 de 4,0 µg/mL y una EC50 de 1,0 µg/mL, respectivamente. Ambas muestras exhibieron un patroÌn dosis-dependiente (r = -0,79, p = 0,03) determinado por anaÌlisis de regresioÌn lineal.
Subject(s)
Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Plant Leaves/chemistry , Casearia , Cell Line, Tumor/drug effects , Sesquiterpenes/analysis , Chromatography, Gas/methods , Nanostructures , EmulsionsABSTRACT
@#With the rapid development of nanotechnology and in-depth understanding of tumor microenvironment, stimuli-responsive smart drug delivery nanosystem based on tumor microenvironment(TME)has received extensive attention. TME-responsive smart delivery nanosystem can transport antitumor drug in circulation stably, after arriving in tumor tissue or targeted cells, the structure of nanocarriers changes under the stimuli of TME. Improved drug concentrations in targeted site significantly increase the antitumor efficiency and reduce the side effects of drugs. The stimulating factors in the TME include pH, redox potential, enzyme, reactive oxygen species(ROS), adenosine-5′-triphosphate(ATP)and so on. This review mainly gives a comprehensive overview in the latest research and new development in TME-responsive smart drug delivery nanosystems for efficient tumor therapy, mainly based on pH response type, enzyme response, reduction response, ROS response, and ATP response smart drug delivery nanosystems. Moreover, research directions in the future are pointed out in this review.
ABSTRACT
Oral drug-loaded nano-system include nano-gel drug delivery system, nano-suspension drug delivery system, nano-particle drug delivery system, liposomes drug delivery system, nano-micelles drug delivery system, alcohol liposoms,nano-framework drug delivery system, nano-emulsions drug delivery system, nano-self assembly drug delivery system.These nano-drug delivery systems can serve as multi-functional drug carriers.They may significantly improve the physicochemical and stabilization and biological properties of the free drug, enhance the therapeutic efficiency and reduce toxic side effects.This paper reviews the recent research progress in oral drug-loaded nano-systems.