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In order to better evaluate the transport effect of nanoparticles through the nasal mucosa, an nasal cavity-mimic model was designed based on M cells. The differentiation of M cells was induced by co-culture of Calu-3 and Raji cells in invert model. The ZO-1 protein staining and the transport of fluorescein sodium and dexamethasone showed that the inverted co-culture model formed a dense monolayer and possessed the transport ability. The differentiation of M cells was observed by up-regulated expression of Sialyl Lewis A antigen (SLAA) and integrin 1, and down-regulated activity of alkaline phosphatase. After targeting M cells with iRGD peptide (cRGDKGPDC), the transport of nanoparticles increased. , the co-administration of iRGD could result in the increase of nanoparticles transported to the brain through the nasal cavity after intranasal administration. In the evaluation of immune effect , the nasal administration of OVA-PLGA/iRGD led to more release of IgG, IFN-, IL-2 and secretory IgA (sIgA) compared with OVA@PLGA group. Collectively, the study constructed M cell model, and proved the enhanced effect of targeting towards M cell with iRGD on improving nasal immunity.
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Accurate tumor targeting, deep penetration and superb retention are still the main pursuit of developing excellent nanomedicine. To achieve these requirements, a stepwise stimuli-responsive strategy was developed through co-administration tumor penetration peptide iRGD with shape-transformable and GSH-responsive SN38-dimer (d-SN38)-loaded nanoparticles (d-SN38@NPs/iRGD). Upon intravenous injection, d-SN38@NPs with high drug loading efficiency (33.92 ± 1.33%) could effectively accumulate and penetrate into the deep region of tumor sites with the assistance of iRGD. The gathered nanoparticles simultaneously transformed into nanofibers upon 650 nm laser irradiation at tumor sites so as to promote their retention in the tumor and burst release of reactive oxygen species for photodynamic therapy. The loaded d-SN38 with disulfide bond responded to the high level of GSH in tumor cytoplasm, which consequently resulted in SN38 release and excellent chemo-photodynamic effect on tumor.
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Objective To construct a glioma targeting delivery system, PAMAM G5 were modified with the oligopeptide of blood brain barrier (BBB) targeting TGN and tumor targeting oligopeptide iRGD to solve the problem of non-specificity in distribution and difficulty in permeating BBB of ATO, in order to have better anti-glioma effect. Methods The physical and chemical properties of nanocarriers were investigated by 1H-NMR and transmission electron microscopy (TEM); The encapsulation efficiency and in vitro release were analyzed by inductively coupled plasma emission spectrum (ICP) and dialysis bag method; The effects of iRGD and TGN on cellular uptake of the carriers were analyzed by laser confocal and flow cytometry. The cytotoxicity of nanocarriers on brain microvascular endothelial cells (HBMEC) and glioma cells (U87), the inhibition effect on U87 cells of drug delivery systems after acrossing the BBB model in vitro were investigated by MTT method. Results The iRGD/TGN-PEG-PAMAM was synthesized successfully. The TEM results showed that iRGD/TGN-PEG-PAMAM was regular in shape and uniform in size. The particle size of iRGD/TGN-PEG-PAMAM/ATO was (24.87 ± 0.84) nm and the potential was (17.26 ± 1.64) mV. The synthesized carrier had less toxicity to HBMEC and U87 cells. The encapsulation efficiency of iRGD/TGN-PEG-PAMAM/ATO delivery system was (71.92 ± 1.17)%. The in vitro release showed that ATO had a slow release trend after entrapment, and it was more favorable for ATO release under acidic conditions. The cell uptake indicated that iRGD/TGN modification was more beneficial for U87 cell to uptake the drug delivery system. The in vitro inhibition effect on U87 cells after acrossing the BBB model showed iRGD/TGN-PEG-PAMAM/ATO had better inhibition effect on U87 cells. Conclusion The iRGD/TGN-PEG-PAMAM/ATO targeting drug delivery system has good inhibition effect on U87 cells effect after acrossing the BBB model in vitro, which provides a new strategy for the treatment of glioma.
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Objective To fabricate iRGD targeted liposome-microbubble complex containing uPA ( iRGD-LMC) ,and to improve the thrombolytic efficiency and reduce the risk of thrombolysis by iRGD-LMC combining with ultrasound targeted microbubbles destruction ( UTMD ) to release drug into the thrombus site with the help of microbubble cavitation effect . Methods Biotinylated iRGD-MBs were fabricated by thin-film rehydration method .Biotinylated liposomes containing uPA were fabricated by freeze-thaw method and were conjugated to the biotinylated iRGD-MBs surface through biotin-avidin linkage . The iRGD-LMC was subjected to confocal microscopy to determine the particle morphology . The concentration , average diameter and size distribution were determined by particle sizing instrument . The uPA loading efficiency was measured by BCA Protein Assay Kit . Ultrasound imaging was performed using a Vevo 2100 ultrasound imaging system . The iRGD-LMC was irradiated by different ultrasound time and intensity to release drug . Thrombolytic effect in vitro of iRGD-LMC combined with UTMD was observed on the thrombosis model which was extracted from mouse blood . Results iRGD-LMC was successfully prepared . iRGD-LMC was exhibited a well-defined spherical morphology and homogeneous distribution ,like ordinary microbubbles . The concentration of iRGD-LMC was ( 0 .51 ± 0 .03 ) × 109 / ml and average diameter was ( 2 .62 ± 0 .12) μm . Drugs loading efficiency was ( 3878 .5 ± 97 .8) μg uPA per 108 microbubbles . iRGD-LMC could achieve contrast-enhanced ultrasound imaging in vitro . The thrombolytic effect of iRGD-LMC +US group ( 87 .66 ± 1 .69) ％ was the best in vitro ,and had significant difference with others groups ( P <0 .05) ,followed by iRGD-LMC group ( 53 .32 ± 4 .86) ％ and uPA group ( 51 .09 ± 9 .01) ％ ,Compared with PBS group ,US group ( 23 .56 ± 9 .46) ％ had thrombolytic effect . Conclusions iRGD-LMC is successfully prepared ,which has the advantages of high drug loading of liposomes and good acoustic properties of microbubbles . iRGD-LMC combined with UTMD achieves a significant thrombolytic effect in vitro .
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In recent years, conventional targeting of chemotherapeutic drugs on colorectal tumor tissue is poor in the clinical application. Due to the multidrug resistance of colorectal tumors, penetration and cytotoxicity of conventional drugs greatly reduced on tumor tissue. With the advent of tumor-penetrating peptides, a new and highly effective antitumor drug delivery system has become a research topic of international scholars. This article will briefly describe the research progress of iRGD peptides with the modified nanomicelles drug delivery system on targeted drug delivery and resistance to drug-resistant colorectal tumors in recent years. These studies show that iRGD peptide-modified nanomicelles will be a highly potential anti-drug delivery system.
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Objective To prepare Integrin αvβ3/CCR2 dual targeted microbubble,test physical-chemical properties,enhancement effect and targeting ability in vitro.Methods The dual targeted microbubbles (MBdual-target )with FITC labled iRGD and PE labled CCR2 were prapared,and non-target microbubbles as control (MBcontrol ) were prapered.Physical and chemical properties of two groups of microbubbles were tested,connectivity of peptides/antibodies and microbubbles were detected by fluorescence microscope and flow cytometry instrument.Enhancement effect and the stability of two groups of microbubbles was observed and compared in vitro.The affinity of MBdual-target and MBcontrol for bEnd.3 cells was investigated with light and fluorescent microscope.Results ①The particle size of MBdual-target was (0.93±0.23)μm,with no statistically significant difference compared with MBcontrol (P >0.05).②MBcontrol showed no fluorescent,while MBdual-target showed both clear green and red light,under fluorescent microscope.③There was no significant difference of gray scale of enhancement between MBdual-target and MBcontrol in vitro.④ It was showed that MBdual-target adhered to bEnd.3 cells in vitro experiment.Conclusions Integrinαvβ3/CCR2 dual targeted targeted microbubbles was successfully prepared and proved having good enhancement effect and targeting ability in vitro.
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Objective To prepare iRGD modified liposome(iRGD-LP)and evaluate their targeting efficiency in vitro and in vivo to colon cancer cell.Methods The iRGD-LP was prepared by film-ultrasonic method,its particle size and Zeta potential were evaluated.The cellular uptake efficiency of RKO cell to LP and iRGD-LP were evaluated in vitro and in vivo.Tumor spheroid model were constructed and the penetration efficiency of solid tumor were evaluated.Ectopic colon cancer nude mice model was constructed,and iRGD -LP distribution in the rat body were studied.Results The particle diameter of iRGD-LP was (109.4 ±12.9)nm with the Zeta potential of (4.2 ±1.47)mV.The cellular uptake efficiency of RKO cell to iRGD-LP were 3.2 times higher than that of LP(P<0.01).The tumor spheroid penetration test and iRGD-LP distribution in vivo imaging results showed iRGD-LP had the strongest fluorescence intensity.Conclusion The iRGD-LP might serve as a promising colon cancer delivery system of antitumor drugs.