Due to the low bioavailability and severe toxic side effects caused by the lack of selectivity of traditional chemotherapy drugs, the targeted delivery of chemotherapy drugs has become the key to tumor treatment. The activity and transmembrane potential of mitochondria in cancer cells were significantly higher than that of normal cells, making them a potential target for chemotherapeutic drug delivery. In this study, triphenylphosphine (TPP) based mitochondria targeting polylactic acid (PLLA) nanoparticles (TPP-PLLA NPs) were synthesized to improve the delivery efficiency of anticancer drugs. The carrier material was characterized by 1H NMR and FT-IR and 7-hydroxyl coumarin (7-HC) was successfully loaded into TPP-PLLA to form 7-HC/TPP-PLLA NPs. Further studies showed that TPP-PLLA NPs were primarily accumulated in the mitochondrial and 7-HC/TPP-PLLA NPs had higher antitumor activity. Taken together, our results indicated that TPP-PLLA NPs could be a promising mitochondria-targeted drug delivery system for cancer therapy.
The proposed study was to develop the preparation of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) modified with citric acid, with surface conjugated with lactoferrin (Lf), which used as a potential targeted contrast agent for magnetic resonance imaging (MRI) of brain glioma. USPIONs were prepared by the thermal decomposition method. The hydrophobic USPIONs were coated with citric acid by the ligand exchange method. Then, Lf was conjugated into the surface of USPIONs. The obtained Lf-USPIONs were analyzed by fourier transform infrared (FTIR) spectroscopy and polyacrylamide gel electrophoresis. The size, size distribution, shape and superparamagnetic property of Lf-USPIONs were investigated with TEM and vibrating sample magnetometer (VSM). Both FTIR and electrophoresis analysis demonstrated the successful conjugation of Lf to the surface of USPIONs. The average size of Lf-USPIONs was about 8.4 ± 0.5 nm, which was determined using the statistics of measured over 100 nanoparticles in the TEM image, with a negative charge of −7.3 ± 0.2 mV. TEM imaging revealed that Lf-USPIONs were good in dispersion and polygonal in morphology. VSM results indicated that Lf-USPIONs were superparamagnetic and the saturated magnetic intensity was about 69.8 emu/g. The Lf-USPIONs also showed good biocompatibility in hemolysis, cytotoxicity, cell migration and blood biochemistry studies. MR imaging results in vitro and in vivo indicated that Lf-USPIONs exhibited good negative contrast enhancement. Taken together, Lf-USPIONs hold great potential for brain gliomas MR imaging as a nanosized targeted contrast agent.
In the study reported here, polylactic acid (PLLA) polymer was synthesized using stannous octoate (Sn(Oct)2) and N-(t-butoxycarbonyl) ethanolamine (EABoc) as the catalyst and the initiator, respectively. The selected PLLA polymer with proper molecular weight was used to prepare nanobubbles encapsulating with liquid perfluoropentane. Then, lactoferrin (Lf), which has a good affinity with tumor cells, was conjugated to PLLA nanobubbles. The resulting Lf–PLLA nanobubbles were examined from the perspective of appearance, size, zeta potential, and stability in vitro. The average hydrodynamic diameter of the Lf–PLLA nanobubbles was 315.3 ± 4.2 nm, the polydispersity index (PDI) was 0.153 ± 0.020, and the zeta potential was around −11.3 ± 0.2 mV. Under the transmission electron microscope (TEM), Lf–PLLA nanobubbles were highly dispersed and had a spherical shape with a distinct capsule structure. The Lf–PLLA nanobubbles also showed little cytotoxicity and low hemolysis rate and exhibited good stability in vitro. The enhanced ultrasound imaging ability of Lf–PLLA nanobubbles was detected by an ultrasound imaging system. The results of ultrasound studies in vitro showed that the liquid perfluoropentane underwent phase transition under ultrasonic treatment, which proved the Lf–PLLA nanobubbles could enhance the ability of ultrasonic imaging. The studies of ultrasonic imaging in nude mice bearing subcutaneous tumors showed that the ability of enhanced ultrasonic images was apparent after injection of Lf–PLLA nanobubbles. Acoustic behavior in vitro and in vivo showed that the Lf–PLLA nanobubbles were characterized by strong, stabilized, and the ability of tumor-enhanced ultrasound imaging. Thus, the Lf–PLLA nanobubbles are an effective ultrasound contrast agent for contrast-enhanced imaging.
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