Maleimide-Functionalized Liposomes for Tumor Targeting via In Situ Binding of Endogenous Albumin

2021 ◽  
Vol 17 (12) ◽  
pp. 2382-2390
Author(s):  
Hanmei Li ◽  
Chuane Tang ◽  
Qi Tang ◽  
Dan Yin ◽  
En He ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Thiol Groups ◽  
Targeting Efficiency ◽  
Transmission Electron ◽  
Chemical Coupling ◽  
4T1 Cells ◽  
Maleimide Group ◽  
Endogenous Albumin

Albumin, the most abundant protein in plasma, has been widely used in drug delivery studies. Here, we developed maleimide-functionalized liposomes (Mal-Lip) that can bind to endogenous albumin to improve the tumor targeting efficiency of liposomes. Transmission electron microscopy and gel electrophoresis studies showed that albumin can bind to Mal-Lip due to the chemical coupling of the albumin thiol groups with the maleimide group. Both conventional liposomes and Mal-Lip showed minimal cytotoxicity within the tested range of lipid concentrations, indicating that the maleimide functionality did not increase the toxicity of liposomes to various cells. Mal-Lip was taken up by 4T1 cells to a greater extent than conventional liposomes, and Mal-Lip accumulated in 4T1 tumors in mice more than conventional liposomes after intravenous injection. These results suggest that the maleimide group can improve the tumor targeting efficiency of liposomes in vivo by binding to endogenous albumin in situ. However, the maleimide group also enhanced the uptake of Mal-Lip by Raw264.7 cells and shortened their time in circulation, indicating that further studies should be performed to prevent elimination of Mal-Lip by the immune system.

In situlow-immunogenic albumin-conjugating-corona guiding nanoparticles for tumor-targeting chemotherapy

2018 ◽  
Vol 6 (10) ◽  
pp. 2681-2693 ◽  
Author(s):  
Zhenbao Li ◽  
Dan Li ◽  
Qingsong Li ◽  
Cong Luo ◽  
Jing Li ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Targeting

Thein siturecruited albumin corona enables NPs' tumor-targeting and enhanced antitumor activityin vivo.

Facile in situ synthesis of ultrasmall near-infrared-emitting gold glyconanoparticles with enhanced cellular uptake and tumor targeting

Nanoscale ◽  
2019 ◽  
Vol 11 (35) ◽  
pp. 16336-16341 ◽  
Author(s):  
Yaping Wang ◽  
Shufeng Ma ◽  
Zhiyi Dai ◽  
Zhili Rong ◽  
Jinbin Liu
Keyword(s):  
Cellular Uptake ◽  
Tumor Targeting ◽  
Near Infrared ◽  
In Situ Synthesis ◽  
Targeting Efficiency ◽  
Gold Glyconanoparticles

Ultrasmall gold glyconanoparticles with enhanced tumor-targeting efficiency and efficient clearance through both renal and hepatobiliary pathways.

scholarly journals Alendronate/cRGD-Decorated Ultrafine Hyaluronate Dot Targeting Bone Metastasis

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 492
Author(s):  
Eunsol Lee ◽  
Jaeduk Park ◽  
Yu Seok Youn ◽  
Kyung Taek Oh ◽  
Dongin Kim ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Bone Tumors ◽  
Tumor Therapy ◽  
Integrin Αvβ3 ◽  
Tumor Ablation ◽  
Cell Permeability ◽  
Cellular Interactions ◽  
Targeting Efficiency ◽  
Specific Ligand

In this study, we report the hyaluronate dot (dHA) with multiligand targeting ability and a photosensitizing antitumor model drug for treating metastatic bone tumors. Here, the dHA was chemically conjugated with alendronate (ALN, as a specific ligand to bone), cyclic arginine-glycine-aspartic acid (cRGD, as a specific ligand to tumor integrin αvβ3), and photosensitizing chlorin e6 (Ce6, for photodynamic tumor therapy), denoted as (ALN/cRGD)@dHA-Ce6. These dots thus prepared (≈10 nm in diameter) enabled extensive cellular interactions such as hyaluronate (HA)-mediated CD44 receptor binding, ALN-mediated bone targeting, and cRGD-mediated tumor integrin αvβ3 binding, thus improving their tumor targeting efficiency, especially for metastasized MDA-MB-231 tumors. As a result, these dots improved the tumor targeting efficiency and tumor cell permeability in a metastatic in vivo tumor model. Indeed, we demonstrated that (ALN/cRGD)@dHA-Ce6 considerably increased photodynamic tumor ablation, the extent of which is superior to that of the tumor ablation of dot systems with single or double ligands. These results indicate that dHA with multiligand can provide an effective treatment strategy for metastatic bone tumors.

scholarly journals Key-Protease Inhibition Regimens Promote Tumor Targeting of Neurotensin Radioligands

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 528
Author(s):  
Panagiotis Kanellopoulos ◽  
Aikaterini Kaloudi ◽  
Marion de Jong ◽  
Eric P. Krenning ◽  
Berthold A. Nock ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Ace Inhibitor ◽  
Tumor Imaging ◽  
Colon Adenocarcinoma ◽  
Ace Inhibition ◽  
Tumor Uptake ◽  
Protease Inhibition ◽  
Structural Modifications

Neurotensin subtype 1 receptors (NTS1R) represent attractive molecular targets for directing radiolabeled neurotensin (NT) analogs to tumor lesions for diagnostic and therapeutic purposes. This approach has been largely undermined by the rapid in vivo degradation of linear NT-based radioligands. Herein, we aim to increase the tumor targeting of three 99mTc-labeled NT analogs by the in-situ inhibition of two key proteases involved in their catabolism. DT1 ([N4-Gly7]NT(7-13)), DT5 ([N4-βAla7,Dab9]NT(7-13)), and DT6 ([N4-βAla7,Dab9,Tle12]]NT(7-13)) were labeled with 99mTc. Their profiles were investigated in NTS1R-positive colon adenocarcinoma WiDr cells and mice treated or not with the neprilysin (NEP)-inhibitor phosphoramidon (PA) and/or the angiotensin converting enzyme (ACE)-inhibitor lisinopril (Lis). Structural modifications led to the partial stabilization of 99mTc-DT6 in peripheral mice blood (55.1 ± 3.9% intact), whereas 99mTc-DT1 and 99mTc-DT5 were totally degraded within 5 min. Coinjection of PA and/or Lis significantly stabilized all three analogs, leading to a remarkable enhancement of tumor uptake for 99mTc-DT1 and 99mTc-DT5, but was less effective in the case of poorly internalizing 99mTc-DT6. In conclusion, NEP and/or ACE inhibition represents a powerful tool to improve tumor targeting and the overall pharmacokinetics of NT-based radioligands, and warrants further validation in the field of NTS1R-targeted tumor imaging and therapy.

scholarly journals Comparing Gly11/dAla11-Replacement vs. the in-Situ Neprilysin-Inhibition Approach on the Tumor-targeting Efficacy of the 111In-SB3/111In-SB4 Radiotracer Pair

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1015 ◽  
Author(s):  
Emmanouil Lymperis ◽  
Aikaterini Kaloudi ◽  
Panagiotis Kanellopoulos ◽  
Marion de Jong ◽  
Eric Krenning ◽  
...  
Keyword(s):  
Animal Models ◽  
Tumor Targeting ◽  
Cell Uptake ◽  
Tumor Uptake ◽  
Biological Profile ◽  
Biological Responses ◽  
Grpr Antagonist ◽  
The Cost

Background: The GRPR-antagonist 68Ga-SB3 visualized prostate cancer lesions in animal models and in patients. Switching radiometal from 68Ga to 111In impaired tumor targeting in mice, but coinjection of the neprilysin (NEP)-inhibitor phosphoramidon (PA) stabilized 111In-SB3 in circulation and remarkably increased tumor uptake. We herein report on the biological profile of 111In-SB4: 111In-[dAla11]SB3. Methods: The biological responses of 111In-SB3/SB4 were compared in PC-3 cells and animal models. Results: Gly11/dAla11-replacement deteriorated GRPR-affinity (SB4 IC50: 10.7 ± 0.9 nM vs. SB3 IC50: 4.6 ± 0.3 nM) and uptake in PC-3 cells (111In-SB4: 1.3 ± 0.4% vs. 111In-SB3 16.2 ± 0.8% at 1 h). 111In-SB4 was more stable than 111In-SB3, but PA-coinjection stabilized both radiotracers in peripheral mice blood. Unmodified 111In-SB3 showed higher uptake in PC-3 xenografts (8.8 ± 3.0%ID/g) vs. 111In-SB4 (3.1 ± 1.1%ID/g) at 4 h pi. PA-coinjection improved tumor uptake, with 111In-SB3 still showing superior tumor targeting (38.3 ± 7.9%ID/g vs. 7.4 ± 0.3%ID/g for 111In-SB4). Conclusions: Replacement of Gly11 by dAla11 improved in vivo stability, however, at the cost of GRPR-affinity and cell uptake, eventually translating into inferior tumor uptake of 111In-SB4 vs. unmodified 111In-SB3. On the other hand, in-situ NEP-inhibition turned out to be a more efficient and direct strategy to optimize the in vivo profile of 111In-SB3, and potentially other peptide radiotracers.

Locomotion and cell-substratum contacts of Xenopus epidermal cells in vitro and in situ

1980 ◽  
Vol 44 (1) ◽  
pp. 201-223
Author(s):  
G.P. Radice
Keyword(s):  
Wound Closure ◽  
Time Lapse ◽  
Epidermal Cells ◽  
Tissue Cell ◽  
Basal Cells ◽  
Closure Time ◽  
Transmission Electron

Studies of tissue cell locomotion in culture have revealed much about cell motility, but whether behaviour in vitro resembles movement of the same cells in the animal is not clear. To investigate this, I compared the locomotion and cell-substratum contacts of epidermal cells from Xenopus tadpoles, migrating from explants on glass and plastic, with the same cells spreading in vivo during wound closure. Time-lapse cinemicrography showed that in both cases, cells spread by extending broad lamellipodia across the substratum, and did not form microspikes, filopodia, or blebs. The net rate of translocation was significantly slower in vitro, however, because cells both protruded lamellipodia slower and spent more time stationary or withdrawing, compared with cells in situ. The increased fluctuation seemed in part due to greater tension within the expanding sheet in vitro, since when tension was reduced, for example by wounding, the cells spread with less fluctuation and at a greater rate (6.5 micrometers/min compared with 0.77 micrometers/min). Micromanipulation showed that cells adhered to the substratum, both in situ and in vitro, by a broad contact where transmission electron microscopy (TEM) of sectioned material showed the cells to be less than 30 nm from the substratum. A similar separation was observed beneath cells in vitro when viewed in life with interference-reflexion optics (IRM). A few focal contacts (adhesion plaques) were also seen with IRM and TEM of cells in vitro, but were not seen with TEM of cells in situ. Submarginal as well as marginal basal cells of the advancing sheet adhere and spread on the substratum in both situations, whereas cells of the outer layer are passive. Hence, the overall pattern of migration of these cells is similar in vitro and in situ; the differences in rates of movement may be explained in part by the different degree of tension in the epithelium under the 2 conditions.

Radiolabeled dendritic probes as tools for high in vivo tumor targeting: application to melanoma

2015 ◽  
Vol 3 (12) ◽  
pp. 2560-2571 ◽  
Author(s):  
Audrey Parat ◽  
David Kryza ◽  
Françoise Degoul ◽  
Jacqueline Taleb ◽  
Claire Viallard ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Murine Melanoma ◽  
Targeting Efficiency ◽  
Melanoma Model ◽  
Intracellular Target

A small-sized and bifunctional111In-radiolabeled dendron shows highin vivotargeting efficiency towards an intracellular target in a murine melanoma model.

The Use of Advanced Analytical Techniques for Characterization of the Chemical, Physical, and Crystallographic Nature of a Surface

1973 ◽  
Vol 31 ◽  
pp. 132-133 ◽  
Author(s):  
R. E. Herfert
Keyword(s):  
Surface Characterization ◽  
Analytical Techniques ◽  
X Ray Diffraction ◽  
Depth Of Penetration ◽  
X Ray ◽  
The Past ◽  
Transmission Electron ◽  
Scanning Electron

Studies of the nature of a surface, either metallic or nonmetallic, in the past, have been limited to the instrumentation available for these measurements. In the past, optical microscopy, replica transmission electron microscopy, electron or X-ray diffraction and optical or X-ray spectroscopy have provided the means of surface characterization. Actually, some of these techniques are not purely surface; the depth of penetration may be a few thousands of an inch. Within the last five years, instrumentation has been made available which now makes it practical for use to study the outer few 100A of layers and characterize it completely from a chemical, physical, and crystallographic standpoint. The scanning electron microscope (SEM) provides a means of viewing the surface of a material in situ to magnifications as high as 250,000X.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

Sign in / Sign up

Export Citation Format

Share Document