Peptide-conjugated PEGylated PAMAM as a highly affinitive nanocarrier towards HER2-overexpressing cancer cells

RSC Advances ◽  
2016 ◽  
Vol 6 (109) ◽  
pp. 107337-107343 ◽  
Author(s):  
Iman Rostami ◽  
ZiJian Zhao ◽  
ZiHua Wang ◽  
WeiKai Zhang ◽  
Yeteng Zhong ◽  
...  

Efficient drug delivery to the tumor cells was carried out with HER2 targeting peptide-conjugated PEGlyted PAMAM.

2021 ◽  
Vol 20 ◽  
pp. 153303382110278
Author(s):  
Yayan Yang ◽  
Qian Feng ◽  
Chuanfeng Ding ◽  
Wei Kang ◽  
Xiufeng Xiao ◽  
...  

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.


2020 ◽  
Author(s):  
Lei Wang ◽  
Xusha Zhou ◽  
Weixuan Zou ◽  
Yinglin Wu ◽  
Jing Zhao ◽  
...  

Abstract Background: Exosomes are small, cellular membrane-derived vesicles with a diameter of 50-150 nm. Exosomes are considered ideal drug delivery systems with a wide range of applications in various diseases, including cancer. However, nonspecific delivery of therapeutic agents by exosomes in vivo remains challenging. H uman epidermal growth factor receptor 2 (HER2) is an epidermal growth factor receptor tyrosine kinase, and its overexpression is usually associated with cell survival and tumor progression in various cancers. In this study, we aim to develop novel exosomes with dual HER2-targeting ability as a nanoparticle delivery vehicle to enhance antitumor efficacy in vivo . Results: Here, we report the generation of two kinds of exosomes carrying miRNAs designed to block HER2 synthesis and consequently kill tumor cells. 293-miR-HER2 exosomes package and deliver designed miRNAs to cells to block HER2 synthesis. These exosomes kill cancer cells dependent on HER2 for survival but do not affect cells that lack HER2 or that are engineered to express HER2 but are not dependent on it for survival. In contrast, 293-miR-XS-HER2 exosomes carry an additional peptide, which enables them to adhere to HER2 on the surface of cancer cells. Consequently, these exosomes preferentially enter and kill cells with surface expression of HER2. 293-miR-XS-HER2 exosomes are significantly more effective than the 293-miR-HER2 exosomes in shrinking HER2-positive tumors implanted in mice. Conclusions: Collectively, as novel antitumor drug delivery vehicles, HER2 dual-targeting exosomes exhibit increased target-specific delivery efficiency and can be further utilized to develop new nanoparticle-based targeted therapies.


RSC Advances ◽  
2014 ◽  
Vol 4 (47) ◽  
pp. 24736-24746 ◽  
Author(s):  
Xueling He ◽  
Mingming Ding ◽  
Jiehua Li ◽  
Hong Tan ◽  
Qiang Fu ◽  
...  

Biodegradable polyurethanes bearing varied amounts of disulfide linkages in the backbone can rapidly enter tumor cells and efficiently transport the encapsulated payloads into cytosol, resulting in controlled inhibition effects against cancer cells. The nanocarriers are promising candidates for on-demand intracellular drug delivery applications.


2021 ◽  
Vol 9 (01) ◽  
pp. 1056-1057
Author(s):  
M. Lavanya ◽  

In this article, targeted and controlled anticancer drug delivery and release with magneto-electric nanoparticles, published in 2016, rodzinski et al., explain how magneto-electric nanoparticles abbreviated as (mens) can be used to monitor the delivery of drugs and their release into cancer cells. They go further to explain how they use this automated drug delivery system to eradicate cancerous tumor cells.


2020 ◽  
Author(s):  
Lei Wang ◽  
Xusha Zhou ◽  
Weixuan Zou ◽  
Yinglin Wu ◽  
Jing Zhao ◽  
...  

Abstract Introduction: Exosomes are small vesicles derived from cellular membranes with a diameter of 50–150 nm. Exosomes are considered to be ideal drug delivery systems with a wide range of application in various diseases including cancer. However, nonspecific delivery of therapeutic agents by exosomes in vivo remains a challenging. Human epidermal growth factor receptor 2 (HER2) is an epidermal growth factor receptor tyrosine kinase. Overexpression of HER2 is usually associated with cancer survival and progression in various cancers. In this study, we aimed to develop the novel exosomes with dual HER2-targeting ability as nanoparticle delivery vehicle to enhance anti-tumor efficacy in vivo.Results Here we report the construction of two kinds of exosomes carrying designed miRNA to block the synthesis of HER2 and as a consequence to kill the tumor cells. The 293-miR-HER2 exosomes package and deliver designed miRNA to cells to block HER2 synthesis. These exosomes kill cancer cells dependent on HER2 for survival but have no effect on cells lacking of HER2 or which were engineered to express HER2 but do not depend on it for survival. The 293-miR-XS-HER2 exosomes carry one more peptide, which enables the exosome to adhere HER2 on the surface of the cancer cells. In consequence these exosomes preferentially enter and kill cells exhibiting HER2 on their surface. The 293-miR-XS-HER2 exosomes are significantly more effective in shrinking the size of HER2-positive tumors implanted in mice than the 293-miR-HER2 exosomes.Conclusion Collectively, as novel anti-tumor drug delivery vehicles, the HER2 dual-targeting exosomes has increased target-specific delivery efficiency, which can be further utilized to develop new nanoparticle targeted therapy.


2019 ◽  
Vol 18 (2) ◽  
pp. 40-50
Author(s):  
N. P. Akentieva ◽  
S. S. Shushanov

Introduction . The RHAMM (hyaluronan mediated mobility receptor) is overexpressed in many types of human cancer and increased synthesis of the RHAMM usually correlates with a poor prognostic factor. In this paper, we synthesized the peptide-RYQLHPYR modulating the activity of the RHAMM and examined the therapeutic potential of this RHAMM-targeting peptide as an antitumor agent.Objective . Study the effect of the synthetic peptide RYQLHPYR on viability, apoptosis, necrosis, caspase-3 / 7 activity, and invasion of prostate cancer cells.Materials and methods . The peptide RYQLHPYR was prepared by solid phase synthesis. Human prostate cancer cells (PC3 m-LN4), murine embryonic fibroblasts and murine embryonic fibroblasts (RHAMM- / -). To quantify the effect of the peptide on apoptosis and cell necrosis, ELISAPLUS was used. The activity of caspase-3 / 7 was determined by the colorimetric method. Evaluation of the anti-metastatic effect of the peptide in vitro was evaluated by invasion of cells by quantitative analysis of the area of degradation of fluorescent gelatin.Results . It was found that the peptide RYQLHPYR inhibited the growth of tumor cells PC3 m-LN4 at a concentration of 10 μg / ml (2 × 10–7 M) after 24 h by ~80 %. It was shown that the peptide stimulated the level of apoptosis in cancer cells, approximately 10-fold. It was found that the peptide increased the necrotic death of tumor cells by 2.5 times. During the research it was revealed that the peptide increased the caspase-3 / 7 activity in tumor cells by 2 times. At the same time, it was shown that RHAMM-targeting peptide had no significant effect on apoptosis and necrosis of normal cells (fibroblasts) and fibroblasts (RHAMM- / -). It was found that the peptide inhibited invasion of tumor cells by ~99.86 % at a concentration of 10 μg / ml (2 × 10–7 M).Conclusions . The obtained results indicate that the peptide RYQLHPYR has antitumor activity and, therefore, has a therapeutic potential for the treatment of prostate cancer. 


Micromachines ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1018
Author(s):  
Chang Ryong Lee ◽  
Gun Gyun Kim ◽  
Sung Bum Park ◽  
Sang Wook Kim

This study is based on the principle that superparamagnetic iron oxide nanoparticles (Fe3O4) can be used to target a specific area given that their magnetic properties emerge when an external magnetic field is applied. Cerium oxide (CeO2), which causes oxidative stress by generating reactive oxygen species (ROS) in the environment of tumor cells, was synthesized on the surface of superparamagnetic iron oxide nanoparticles to produce nanoparticles that selectively kill cancer cells. In addition, hyaluronic acid (HA) was coated on the cerium’s surface to target CD44-overexpressing tumor cells, and natZr was chelated on the Fe3O4@CeO2 surface to show the usefulness of labeling the radioisotope 89Zr (T1/2 = 3.3 d). The synthesis of Fe3O4@CeO2 was confirmed by Fourier Transform-Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD) and Field Emission-Transmission Electron Microscope (FE-TEM). The coating of HA was confirmed by FT-IR, X-ray Photoelectron. Spectroscopy (XPS), FE-TEM, Energy-Dispersive X-ray Spectroscopy (EDS) and Thermogravimetric Analysis (TGA)/Differential Scanning Calorimetry (DSC). The sizes of the prepared nanoparticles were confirmed through FE-TEM and Field Emission-Scanning Electron (FE-SEM) (sizes of 15 to 30 nm), and it was confirmed that natZr was introduced onto the surface of the nanoparticles using EDS. The particle size of the dispersed material was limited through Dynamic Light Scattering (DLS) to about 148 nm in aqueous solution, which was suitable for the (enhanced permeation and retention) EPR effect. It was confirmed that the HA-coated nanoparticles have good dispersibility. Finally, a cytotoxicity evaluation confirmed the ability of CeO2 to generate ROS and target the delivery of HA. In conclusion, Fe3O4@CeO2 can effectively inhibit cancer cells through the activity of cerium oxide in the body when synthesized in nano-sized superparamagnetic coral iron that has magnetic properties. Subsequently, by labeling the radioactive isotope 89Zr, it is possible to create a theranostic drug delivery system that can be used for cancer diagnosis.


2021 ◽  
Author(s):  
Priscila Izabel Santos de Totaro

Functionalized nanostructured systems can be used for imaging and drug delivery for anti-tumor therapy, including breast tumors. This is a more efficient approach that offers reduced systemic side effects compared to conventional diagnostic and chemotherapy methods. Multifunctional nanoparticles are potential tools in the diagnosis, location tracing and kill tumor cells through a less invasive manner. Functionalized phosphate-based nanoparticles are capable of encapsulating, or may be associated, with fluorescent probes. In this study, we synthesize a nanoparticle phosphate-based composite (NPC) and functionalize it with poly-ethylene glycol (PEG), hyaluronic acid (HA), the fluorescent probe rhodamin 6G (R6G) and the antimitotic doxorubicin (DOX). We focused on targeting human breast cancer cells reporting the biological effects of functionalized NPC on them. NPC and NPC formulations containing PEG, HA, and R6G did not cause cell viability reduction on MCF-7 and MDA-MB-231 cell lines. The cellular internalization of NPC was quantified by real-time in vitro observation, and confirmed by electron microscopy techniques. Intracellular NPC distribution is detected in the cytoplasm and nucleus of tumor cells by confocal fluorescent images. The percent association of doxorubicin to NPC matrix was approximately 18% and NPC formulations associated with doxorubicin led to a significant reduction in cell viability in MDA-MB-231 and MCF-7 cells. This data suggest the potential use of NPC as a non-cytotoxic platform for association with functional ligands to selective targeting breast cancer cells. NPC use can be also explored in drug delivery to cancer cells.


2020 ◽  
Vol 28 (3) ◽  
pp. 399-405
Author(s):  
Fabrizio Fontana ◽  
Olga A. Babenko

Aim of this letter is to attract the attention of journal readers to the study of exosomes as an important direction in the development of Oncology, in particular, in the diagnosis and treatment of prostate cancer. Exosomes are produced by tumor cells and regulate proliferation, metastasis, and the development of chemoresistance. Their extraction from biological fluids allows further use of these vesicles as potential biomarkers of prostate cancer. In the future, exosomes can be successfully used in the delivery of drugs and other anti-tumor substances to cancer cells.


2019 ◽  
Vol 1 (1) ◽  
pp. 7
Author(s):  
R Nahrowi ◽  
A Setiawan ◽  
Noviany Noviany ◽  
I Sukmana ◽  
S D Yuwono

Paclitaxel is one of the cancer drugs that often used. These drug kills cancer cells byinhibiting mitotic cycle. The efficiency of paclitaxel is increased by the use ofnanomaterials as a carrier of paclitaxel. Nanomaterials can enhance encapsulationefficiency, improve the drug release to the target cell following nanomaterialdegradation, and improve local accumulation of drug in the cell through endocytosisreceptor. Nanomaterial that often used forencapsulation of paclitaxel is a polymerderived from natural resources such as cellulose. The advantages of cellulose as acarrier of paclitaxel are nontoxic, biodegradable, and very abundant from varioussources. One of the potential sources of cellulose for drug delivery system is cassavabaggase.Keywords: Paclitaxel, encapsulation, cell viability, nanocellulose


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