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
OBJECTIVE： To prepare Adriamycin hydrochloride （DOX） magnetic thermosensitive liposome （MTSL）， investigate its physicochemical properties， magnetic effect and photothermal effect， so as to provide reference for tumor chemo- therapy and photodynamic/photothermal therapy. METHODS： Using DOX as model drug， TiO2@Fe3O4 as photosensitizers and magnetic materials， DOX-TiO2@Fe3O4-MTSL was prepared with membrane dispersion method. The morphology and dispersibility were observed； particle size and Zeta potential were detected； encapsulation efficiency of the liposome were determined by centrifugal ultrafiltration and HPLC. Its paramagnetism property was also detected by magnetometer. Compared with DOX solution， in vitro release behavior of the liposome was investigated by dialysis method， and the release curves at different temperatures （at 37， 43 ℃） were compared. The photothermal conversion effect of the liposome and the production of reactive oxygen species （ROS） in human breast cancer MCF-7 cells were investigated by near infrared laser irradiation at 808 nm. RESULTS： Prepared DOX-TiO2@Fe3O4-MTSL was brown-black with good water dispersion， and was spherical in shape and uniform in size under electron microscopy. Average particle size was 250.6 nm； polydispersity index was 0.107； Zeta potential was （－7.76±3.41）mV； encapsulation efficiency was （92.3±3.2）％. Under the external magnetic field， the liposome could move in a directional direction and had obvious paramagnetism. Compared with DOX solution， the liposomes released slowly and showed obvious sustained- release characteristics. Compared with at 37 ℃， the drug release of liposome speeded up significantly at 43 ℃.With the increase of laser （808 nm） irradiation time， the temperature of the liposome kept rising， which had obvious photothermal conversion effect and could induce the increase of ROS in MCF-7 cells. CONCLUSIONS： DOX-TiO2@Fe3O4-MTSL is prepared succe- ssfully， which has uniform appearance， good physical and chemical properties. It has obvious paramagnetism sustained release effect and photothermal conversion efficiency， and can promote ROS production in MCF-7 cells under near infrared laser irradiation at 808 nm.
ABSTRACT
Traditional Chinese medicine (TCM) formula is one of the unique cultural treasures of Chinese. However, only a few studies have been carried out to deliver TCM formula with utilization of nanocarriers. The purpose of this study was to prepare the hydroxypropyl-β-cyclodextrin complex-over-a-poly(lactic-co-glycolic acid) nanoparticle (HP-β-CD-PLGA NP) for co-delivery and sequential release of five main effective ingredients of Danshen and Sanqi to a specific target, which can provide strategies for design of intelligent drug delivery system of TCM formula. PLGA can be employed as scaffolds for sustained release of both hydrophobic and hydrophilic drugs. HP-β-CD could encapsulate the hydrophobic drugs by forming inclusion complexes. Superparamagnetic iron oxide nanoparticles (SPION) embedded inside PLGA nanoparticles that allow a spatio-specific targeting. HP-β-CD inclusion complex was prepared by an unsaturated alcohol solution method. PLGA NP loaded with SPION was obtained through double emulsion-organic solvents evaporation. Then core-shell PLGA nanosystem was formed by co-incubation of the above two materials. The nanoparticulate system was characterized by confocal laser scanning microscopy (CLSM), laser particle size instrument and transmission electron microscope. Magnetic property was determined by magnet adsorption and vibrating sample magnetometer (VSM). Targeted distribution was investigated by cell uptake and sequential release of multiple components was observed by intracellular distribution of fluorescent probes. Release difference of five components between core and shell of HP-β-CD-PLGA NP was measured by high performance liquid chromatography. The results demonstrated that NP had a unique core-shell structure and possessed superpara-magnetism. Magnetic NP could be ingested site-specifically by L929 cells with the aid of magnetic field, and coumarin-6 and rhodamine B were released from NP sequentially in the L929 cells. In vitro release of multiple components of Danshen and Sanqi from NP exhibited double phase time-controlled release kinetics of quick-release shell and sustained-release core. Therefore, the spatio-temporal nanoplatform has a great capacity for unlocking the full therapeutic potential of displaying synergistic efficacy of TCM formula in the formulation design.
ABSTRACT
In this paper, we prepared a dual functional system based on dextrin-coated silver nanoparticles which were further attached with iron oxide nanoparticles and cell penetrating peptide (Tat), producing Tat-modified Ag-FeO nanocomposites (Tat-FeAgNPs). To load drugs, an -SH containing linker, 3-mercaptopropanohydrazide, was designed and synthesized. It enabled the silver carriers to load and release doxorubicin (Dox) in a pH-sensitive pattern. The delivery efficiency of this system was assessed using MCF-7 cells, and using null BalB/c mice bearing MCF-7 xenograft tumors. Our results demonstrated that both Tat and externally applied magnetic field could promote cellular uptake and consequently the cytotoxicity of doxorubicin-loaded nanoparticles, with the IC of Tat-FeAgNP-Dox to be 0.63 µmol/L. The delivery efficiency of Tat-FeAgNP carrying Cy5 to the mouse tumor was analyzed using the optical imaging tests, in which Tat-FeAgNP-Cy5 yielded the most efficient accumulation in the tumor (6.7±2.4% ID of Tat-FeAgNPs). Anti-tumor assessment also demonstrated that Tat-FeAgNP-Dox displayed the most significant tumor-inhibiting effects and reduced the specific growth rate of tumor by 29.6% ( = 0.009), which could be attributed to its superior performance in tumor drug delivery in comparison with the control nanovehicles.
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Chemotherapy is one of the traditional tumors treatment solutions.Chemotherapy has the feature of tissue non-specificity,which can cause side effects on normal cells while inhibiting tumor cell growth.Magnetic targeting drug delivery system (MTDDS) employs biocompatible and stable magnetic nanoparticles (MNP) as drug carries to transport and accumulate anticancer drugs to the specific tumor tissues under the guidance of external magnetic field.This technology not only improves the efficiency of drug delivery and antitumor activity,but also reduces the drug dosage and side effects.The properties of drug-loaded MNPs and the applied external magnetic field are the main factors that affecting the MNPs targeting to the tumor tissues.The effectiveness of the targeted delivery of the drug-loaded magnetic nanoparticles mainly depends on the form and strength of the magnetic field at the target site.That is,whether there is sufficient strength to attract and retain NMPs,and to promote antitumor drug release at the tumor region.In this paper,the research progress of static magnetic field targeting drug delivery system in tumor diagnosis and therapy was summarized,which can provide some basic information for the relative scientific researches.
ABSTRACT
Erectile dysfunction (ED) is a major complication of diabetes, and many diabetic men with ED are refractory to common ED therapies. Adipose tissue-derived stem cells (ADSCs) have been shown to improve erectile function in diabetic animal models. However, inadequate cell homing to damaged sites has limited their efficacy. Therefore, we explored the effect of ADSCs labeled with superparamagnetic iron oxide nanoparticles (SPIONs) on improving the erectile function of streptozotocin-induced diabetic rats with an external magnetic field. We found that SPIONs effectively incorporated into ADSCs and did not exert any negative effects on stem cell properties. Magnetic targeting of ADSCs contributed to long-term cell retention in the corpus cavernosum and improved the erectile function of diabetic rats compared with ADSC injection alone. In addition, the paracrine effect of ADSCs appeared to play the major role in functional and structural recovery. Accordingly, magnetic field-guided ADSC therapy is an effective approach for diabetes-associated ED therapy.
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Objective To prepare doxorubicin-loaded pH/magnetic dual responsive nanocomplex denoted as Fe3O4@SiO2 @PEG-6-PAsp@DOX and to determine its chemo-physical properties, pH/magnetic dual responsive release, and cytotoxicity against human lung cancer A549 cells. Methods The nanocomplex was synthesized through a sequential process involving hydrothermal treatment, Stober method, sol-gel technique, and cross-linking. The morphology, diameter, zeta potential and magnetic properties of the nanocomplex were characterized by transmission electron microscopy, zeta potential measurement analyzer, and hysteresis loop tester, respectively. Drug loading efficiency and encapsulation efficiency were examined by ultraviolet visible absorption spectroscopy; pH-stimulated drug release was investigated by dialysis in vitro; and the antiproliferative activity apoptosis-induction effect of the complex nanoparticles were investigated by CCK-8 method and flow cytometer, respectively. Results The average particle size of drug-loaded system Fe3O4 @ SiO2 @ PEG-b-PAsp @ DOX was (197. 7±1. 5) nm and the zeta potential was (— 35. 9 ± 0. 6) mV. Drug loading efficiency and encapsulation efficiency were20. 36 ± 0. 67) % and (83. 71 ± 0. 53) %, respectively. Cumulative release rate was significantly increased in mild acid condition (pH = 5. 5) (P<0. 05). The nanocomplex also demonstrated a good magnetic response and targeting ability under outside magnetic field. Moreover, the drug-loaded nanoparticle showed a significant cytotoxicity effect against human lung A549 cells in vitro. Conclusion Fe3O4 @ SiO2 @ PEG-b-PAsp @ DOX possesses a good pH/magnetic dual responsive release characteristics and exhibits efficient antitumor activity in vitro against lung cancer A549 cells.
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Coupled magnetic nanoparticles in the microcapsule structure, such as magnetic microcapsules, can be delivered in specific organism or tissues under magnetic field exposure. Thus, the microcapsules can achieve active targeting functions by manipulat-ing the magnetic field. Based on the magnetic microcapsules, the antitumor drugs can also be loaded to realize magnetic response, which gives microcapsules sustained and controlled release advantages. To date, the drug microcapsules carrying magnetic nanoparti-cles have become promising novel delivery carriers for the treatment of tumor diseases. This paper mainly reviews the method of prepa-ration of the magnetic nanoparticle-coupled microcapsules, including liposomes, polyelectrolyte microcapsules, and polymer micro-spheres. The basic research progress of these microcapsules as anticancer drug carriers for the tumor therapy was also reviewed.
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To assess a novel cell manipulation technique of tissue engineering with respect to its ability to augment superparamagnetic iron oxide particles (SPIO) labeled mesenchymal stem cells (MSCs) density at a localized cartilage defect site in an in vitro phantom by applying magnetic force.Meanwhile,non-invasive imaging techniques were use to track SPIO-labeled MSCs by magnetic resonance imaging (MRI).Human bone marrow MSCs were cultured and labeled with SPIO.Fresh degenerated human osteochondral fragments were obtained during total knee arthroplasty and a cartilage defect was created at the center.Then,the osteochondral fragments were attached to the sidewalls of culture flasks filled with phosphate-buffered saline (PBS) to mimic the human joint cavity.The SPIO-labeled MSCs were injected into the culture flasks in the presence of a 0.57 Tesla (T) magnetic force.Before and 90 min after cell targeting,the specimens underwent T2-weighted turbo spin-echo (SET2WI) sequence of 3.0 T MRI.MRI results were compared with histological findings.Macroscopic observation showed that SPIO-labeled MSCs were steered to the target region of cartilage defect.MRI revealed significantchanges in signal intensity (P＜0.01).HE staining exibited that a great number of MSCs formed a three-dimensional (3D) cell "sheet" structure at the chondral defect site.It was concluded that 0.57 T magnetic force permits spatial delivery of magnetically labeled MSCs to the target region in vitro.High-field MRI can serve as an very sensitive non-invasive technique for the visualization of SPIO-labeled MSCs.