Objective To prepare and characterize a novel liposome which could be used for targeted synergistic chemo-photothermal cancer therapy. Methods Hydrophilic nano copper sulfide(PVP/CuS)was chosen as the near infrared photothermal agent, and doxorubicin hydrochloride(DOX)was used as the model chemo-therapeutic agent. DOX-PVP/CuS-Lip was successfully prepared by the membrane dispersion method. The zeta potential and particle size of DOX-PVP/CuS-Lip were determined by using Darwin laser particle size analyzer. The morphology was observed by TEM. The encapsulation efficiency was determined by the ultrafiltration centrifugation method. The characteristics of photothermal conversion were measured under near-infrared irradiation. And dialysis method was used for in vitro drug release test. Results DOX-PVP/CuS-Lip was spherical and uniform in size. The average particle size and zeta potential were 200.9 nm(PDI=0.43)and (-16.0±0.9) mV, respectively. The encapsulation efficiency and drug loading ratio were (91.0±2.0)% and (11.02±0.2)%, respectively. DOX-PVP/CuS-Lip had obvious photothermal conversion effect under near-infrared irradiation at 808 nm in a time-dependent manner. The in vitro drug release test showed that the formulation had obvious sustained release characteristics compared with DOX solution, and the release rate at 45 ℃ was significantly higher than that at 37 ℃. Conclusion The preparation process of DOX-PVP/CuS-Lip was stable and feasible. And the prepared DOX-PVP/CuS-Lip had obvious photo-thermal conversion efficiency and temperature dependent drug release characteristics.
Fig.3
Size and Zeta potential distribution A-B.Size distribution of Blank-Lip and DOX-PVP/CuS-Lip;C-D.Zeta potential distribution of Blank-Lip and DOX-PVP/CuS-Lip.
ZHANGH,ZHANGY,JINR,et al.Preparation and photo-thermal therapy of hyaluronic acid-conjugated Au nanoparticle-coated poly(glycidyl methacrylate)nanocomposites[J].J Materials Sci,2018,53(24):16252-16262.
TIANQ,TANGM,SUNY,et al.Hydrophilic flower-like Cu S superstructures as an efficient 980 nm laser-driven photothermal agent for ablation of cancer cells[J].Adv Mater,2011,23(31):3542-3547.
RIEDINGERA,AVELLINIT,CURCIOA,et al.Post-synthesis incorporation of 64Cu in CuS nanocrystals to radiolabel photothermal probes:a feasible approach for clinics[J].J Am Chem Soc,2015,137(48):15145-15151
We report a simple method for the incorporation of Cu(I) or (64)Cu(I) radionuclides in covellite nanocrystals (CuS NCs). After the in situ reduction of Cu(II) or (64)Cu(II) ions by ascorbic acid, their incorporation in PEG-coated CuS NCs takes place at room temperature. In all the reaction steps, the stability of the NCs under physiological conditions was ensured. The copper incorporation reaction could also take place on CuS NCs bearing biotin molecules at their surface, with no detrimental effects on the specific binding affinity of the NCs toward streptavidin after incorporation. At low loading of Cu ions, the strong near-infrared (NIR) absorption band of the starting CuS NCs was essentially preserved, which allowed for efficient plasmonic photothermal therapy. The combined presence in the NCs of (64)Cu ions, well suitable for positron emission tomography, and of free carriers responsible for the NIR absorption, should enable their theranostic use as radiotracers and as photothermal probes in tumor ablation treatments. Moreover, the simplicity of the preparation scheme, which involves the use of radioactive species only as a last step, makes the protocol easily transferable to the clinical practice.
HARDIANSYAHA,YANG MC,LIUTY,et al.Hydro-phobic drug-loaded pegylated magnetic liposomes for drug-controlled release[J].Nanoscale Res Lett,2017,12(1):355-365.
Less targeted and limited solubility of hydrophobic-based drug are one of the serious obstacles in drug delivery system. Thus, new strategies to enhance the solubility of hydrophobic drug and controlled release behaviors would be developed. Herein, curcumin, a model of hydrophobic drug, has been loaded into PEGylated magnetic liposomes as a drug carrier platform for drug controlled release system. Inductive magnetic heating (hyperthermia)-stimulated drug release, in vitro cellular cytotoxicity assay of curcumin-loaded PEGylated magnetic liposomes and cellular internalization-induced by magnetic guidance would be investigated. The resultant of drug carriers could disperse homogeneously in aqueous solution, showing a superparamagnetic characteristic and could inductive magnetic heating with external high-frequency magnetic field (HFMF). In vitro curcumin release studies confirmed that the drug carriers exhibited no significant release at 37 degrees C, whereas exhibited rapid releasing at 45 degrees C. However, it would display enormous (three times higher) curcumin releasing under the HFMF exposure, compared with that without HFMF exposure at 45 degrees C. In vitro cytotoxicity test shows that curcumin-loaded PEGylated magnetic liposomes could efficiently kill MCF-7 cells in parallel with increasing curcumin concentration. Fluorescence microscopy observed that these drug carriers could internalize efficiently into the cellular compartment of MCF-7 cells. Thus, it would be anticipated that the novel hydrophobic drug-loaded PEGylated magnetic liposomes in combination with inductive magnetic heating are promising to apply in the combination of chemotherapy and thermotherapy for cancer therapy.
ZOUJ,FENGH,SOODR,et al.Biocompatibility of liposo-me nanocarriers in the rat inner ear after intratympanic administration[J].Nanoscale Res Lett,2017,12(1):372.
Liposome nanocarriers (LPNs) are potentially the future of inner ear therapy due to their high drug loading capacity and efficient uptake in the inner ear after a minimally invasive intratympanic administration. However, information on the biocompatibility of LPNs in the inner ear is lacking. The aim of the present study is to document the biocompatibility of LPNs in the inner ear after intratympanic delivery. LPNs with or without gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) were delivered to the rats through transtympanic injection. The distribution of the Gd-DOTA-containing LPNs in the middle and inner ear was tracked in vivo using MRI. The function of the middle and inner ear barriers was evaluated using gadolinium-enhanced MRI. The auditory function was measured using auditory brainstem response (ABR). The potential inflammatory response was investigated by analyzing glycosaminoglycan and hyaluronic acid secretion and CD44 and TLR2 expression in the inner ear. The potential apoptosis was analyzed using terminal transferase (TdT) to label the free 3'OH breaks in the DNA strands of apoptotic cells with TMR-dUTP (TUNEL staining). As a result, LPNs entered the inner ear efficiently after transtympanic injection. The transtympanic injection of LPNs with or without Gd-DOTA neither disrupted the function of the middle and inner ear barriers nor caused hearing impairment in rats. The critical inflammatory biological markers in the inner ear, including glycosaminoglycan and hyaluronic acid secretion and CD44 and TLR2 expression, were not influenced by the administration of LPNs. There was no significant cell death associated with the administration of LPNs. The transtympanic injection of LPNs is safe for the inner ear, and LPNs may be applied as a drug delivery matrix in the clinical therapy of sensorineural hearing loss.
ZHUX,HUANGH,ZHANGY,et al.Cit/CuS at FeO-based and enzyme-responsive magnetic nanoparticles for tumor chemotherapy,photothermal,and photodynamic therapy[J].J Biomater Appl,2017,31(7):1010-1025.
Safe and efficient drug delivery in a controllable fashion, especially remote and repeatable switch of on-demand drug release, is the subject of widespread attention. A kind of magnetic nanoparticles (DOX-Cit/CuS@Fe3O4-NPs) simultaneously consisted of Cit/CuS@Fe3O4 and doxorubicin (DOX) was presented. The drug release from DOX-Cit/CuS@Fe3O4-NPs could be successfully triggered by the presence of gelatinase, showing great promise for tumor-targeted drug release through an enzymatic degradation mechanism. Compared with free DOX, DOX-Cit/CuS@Fe3O4-NPs could not only specially deliver Cit/CuS@Fe3O4 and DOX into MCF-7 cells, but also could greatly improve the quantity of ROS produced in MCF-7 cells under of 980 nm laser irradiation. DOX-Cit/CuS@Fe3O4-NPs also had highly selective accumulation at tumor tissue of S180 tumor-bearing mice, which were along with a magnet near the tumor site. Furthermore, when combined with NIR laser irridation, DOX-Cit/CuS@Fe3O4-NPs showed a higher antitumor efficacy than the individual therapies in vitro and in vivo. This study showed that DOX-Cit/CuS@Fe3O4-NPs could be used as a platform for tumor chemotherapy, photothermal and photodynamic therapy.
SHIJ,CHENC,PANJ,et al.Efficient remote NIR-Controlled drug delivery into tumor cells by nanoplatform modified with tumoral-acid-cleavable polyethylene glycol[J].J Biomed Nanotechnol,2017,13(9):1019-1034.
Despite advances in controlled drug delivery, drug-delivery systems with controlled activatable drug release and high spatial and temporal resolution are still required. PEGylation has been extensively used to increase the circulation time of controlled drug-delivery systems, but polyethylene glycol (PEG) is unsuitable for uptake by tumor cells because it causes steric hindrance. In this study, a near-infrared (NIR)-light-regulated drug-delivery system with enhanced cellular uptake was developed using a hybrid nanoplatform (GO@Au). GO@Au modified with tumoral-acid-cleavable PEG circumvents the hindrance effect of PEG grafted onto the drug-delivery system without sacrificing the property of a long circulation time. With the application of NIR light, both GO and Au in GO@Au strongly absorb the NIR energy, leading to intense resonance, and causing the release of a significant proportion of the loaded drug. GO@Au retains most of the loaded drug without NIR. We show the feasibility of using this nanocarrier as a targeted, noninvasive remote-controlled drug-delivery system with high spatial and temporal resolution. Integrating chemotherapy and photothermal therapy functions into one system, we investigated the therapeutic effects of DOX-loaded GO@Au-PEG, with highly efficient drug loading. Our in vitro and in vivo results reveal a synergistic effect, enhancing the therapeutic effects of the drugs and reducing their adverse effects. These results highlight the great potential utility of GO@Au-PEG/DOX in the treatment of cancer.
HOSNY KM.Preparation and evaluation of thermosensitive liposomal hydrogel for enhanced transcorneal permeation of ofloxacin[J].Aaps Pharmscitech,2009,10(4):1336-1342.
Ofloxacin, available as ophthalmic solution, has two major problems: first, it needs frequent administration every 4 hours or even every 1 hour to treat severe eye infection; second, there is formation of white crystalline deposit on cornea due to its pH-dependent solubility, which is very low at pH of corneal fluid. In order to provide a solution to previous problems, ofloxacin in this study is prepared as topically effective in situ thermosensitive prolonged release liposomal hydrogel. Two preparation procedures were carried out, leading to the formation of multilamellar vesicles (MLVs) and reverse-phase evaporation vesicles (REVs) at pH 7.4. Effects of method of preparation, lipid content, and charge inducers on encapsulation efficiency were studied. For the preparation of in situ thermosensitive hydrogel, chitosan/beta-glycerophosphate system was synthesized and used as carrier for ofloxacin liposomes. The effect of addition of liposomes on gelation temperature, gelation time, and rheological behaviors of the hydrogel were evaluated. In vitro transcorneal permeation was also determined. MLVs entrapped greater amount of ofloxacin than REVs liposomes at pH 7.4; drug loading was increased by including charge-inducing agent and by increasing cholesterol content until a certain limit. The gelation time was decreased by the addition of liposomes into the hydrogel. The prepared liposomal hydrogel enhances the transcorneal permeation sevenfold more than the aqueous solution. These results suggested that the in situ thermosensitive ofloxacin liposomal hydrogel ensures steady and prolonged transcorneal permeation, which improves the ocular bioavailability, minimizes the need for frequent administration, and decreases the ocular side effect of ofloxacin.
, 李玲华, 王莎莎, 巴妍妍, 贾永艳
