含有靶向系统的化学治疗剂是增加胶质母细胞瘤治疗有效性的有前途的途径。以肿瘤细胞表面表达增加为特征的特定蛋白质被认为是可能的靶标。整合素αvβ3是细胞表面上的此类蛋白质之一。它有效地结合环状Arg-Gly-Asp(cRGD)肽。在这项研究中,研究了cRGD肽修饰的阿霉素(Dox)磷脂组合物。该组合物的粒径为43.76±2.09nm，ζ电位为4.33±0.54mV。Dox几乎完全结合到纳米颗粒中(99.7±0.58%)。药物释放在酸性介质(在约35±3.2%的pH5.0)中增加。与游离形式相比,使用磷脂纳米颗粒与靶向载体的组合物的Dox的总积累和内化高1.4倍。在HeLa细胞系(不表达αvβ3整联蛋白)中未观察到这种作用。这些结果表明在将Dox递送至胶质母细胞瘤细胞中使用环状RGD肽的前景以及进一步研究整个组合物的作用机制的可行性。
Ispol\'zovaniekhimiopreparatov,soderzhashchikhadresnye姐妹多斯塔夫基,神经胶质细胞切开术.Vkachestvemishene而rassmatrivaiutsiaspetsificheskiebelki,埃克斯普莱西亚·科托里克·纳沃克诺斯蒂·奥克霍尔耶克·克莱托克·乌夫利瓦西亚。Takimbelkomiavliaetsia整合素αvβ3,kotoryfiéffektivnosviazyvaettsiklicheskiptidArg-Gli-Asp(cRGD).Vdannoàraboteissledovanafosfolipidnaiakompozitsiiadoksorubitsina（Dox），snabzhennaiacRGD肽。Razmerchastetskompozitsiisostavlial43,76±2,09纳米，ζ-电位sootvetstvoval4,33±0,54mV。Doxprakticheskipolnost\'iuvstrayvaetsiavnanochasticy（99,7±0.58%）。PriizucheniivysvobozhdeniialekarstvavzavisimostitokislotnostisredybyloustanovlenopovyshennoeegovysvobozhdenievkislosrederN5,0(okolo35±3,2%).OtsenkakletochnogonakospleniiapokazalapovyshenieobshchchegonakospleniiaiinternalizatsiiDoxvsosavefosfolipidnykhnananochastitssadresnymvektoromv~1,4razaposravneneniiPRIétomnaliniikletokHeLa（整合蛋白αvβ3）podobnogoéffektanenabliudalos\'.Poluchennyerezul
Chemotherapeutic agents containing targeted systems are a promising pathway to increase the effectiveness of glioblastoma treatment. Specific proteins characterized by increased expression on the surface of tumor cells are considered as possible targets. Integrin αvβ3 is one of such proteins on the cell surface. It effectively binds the cyclic Arg-Gly-Asp (
cRGD) peptide. In this
study, the
cRGD peptide-modified doxorubicin (Dox) phospholipid composition was investigated. The particle size of this composition was 43.76±2.09 nm, the ζ-potential was 4.33±0.54 mV. Dox was almost completely incorporated into the nanoparticles (99.7±0.58%). The drug release increased in an acidic medium (at pH 5.0 of about 35±3.2%). The total accumulation and internalization of Dox used the composition of phospholipid nanoparticles with the targeted vector was 1.4-fold higher as compared to the free form. In the HeLa cell line (not expressing αvβ3 integrin) this effect was not observed. These results suggest the prospects of using the cyclic RGD peptide in the delivery of Dox to glioblastoma cells and the feasibility of further investigation of the mechanism of action of the entire composition as a whole.
Ispol\'zovanie khimiopreparatov, soderzhashchikh adresnye sistemy dostavki, predstavliaet soboĭ perspektivnoe napravlenie povysheniia éffektivnosti lecheniia glioblastomy. V kachestve misheneĭ rassmatrivaiutsia spetsificheskie belki, ékspressiia kotorykh na poverkhnosti opukholevykh kletok uvelichivaetsia. Takim belkom iavliaetsia integrin αvβ3, kotoryĭ éffektivno sviazyvaet tsiklicheskiĭ peptid Arg-Gli-Asp (
cRGD). V dannoĭ rabote issledovana fosfolipidnaia kompozitsiia doksorubitsina (Dox), snabzhennaia
cRGD peptidom. Razmer chastits kompozitsii sostavlial 43,76±2,09 nm, ζ-potentsial sootvetstvoval 4,33±0,54 mV. Dox prakticheski polnost\'iu vstraivaetsia v nanochastitsy (99,7±0,58%). Pri izuchenii vysvobozhdeniia lekarstva v zavisimosti ot kislotnosti sredy bylo ustanovleno povyshennoe ego vysvobozhdenie v kisloĭ srede rN 5,0 (okolo 35±3,2%). Otsenka kletochnogo nakopleniia pokazala povyshenie obshchego nakopleniia i internalizatsii Dox v sostave fosfolipidnykh nanochastits s adresnym vektorom v ~1,4 raza po sravneniiu so svobodnoĭ formoĭ. Pri étom na linii kletok HeLa (ne ékspressiruiushchikh integrin αvβ3) podobnogo éffekta ne nabliudalos\'. Poluchennye rezul\'taty svidetel\'stvuiut o perspektivnosti ispol\'zovaniia tsiklicheskogo RGD peptida v dostavke Dox v kletki glioblastomy i tselesoobraznosti dal\'neĭshego issledovaniia mekhanizma deĭstviia vseĭ kompozitsii v tselom.
