scholarly journals Construction of an exosome-functionalized graphene oxide based composite bionic smart drug delivery system and its anticancer activity

2022 ◽  
Author(s):  
Qi Chen ◽  
Chengchuan Che ◽  
Jinfeng Liu ◽  
Zhijin Gong ◽  
Meiru Si ◽  
...  

Abstract Graphene oxide has covalently modified by chito oligosaccharides and γ-polyglutamic acid to form GO-CO-γ-PGA, which exhibits excellent performance as a drug delivery carrier, but this carrier did not have the ability to actively target. In this study, the targeting property of breast cancer tumor cell exosomes was exploited to give GO-CO-γ-PGA the ability to target breast tumor cells (MDA-MB-231), and the drug mitoxantrone (MIT) was loaded to finally form EXO-GO-CO-γ-PGA-MIT with a loading capacity of 1.39 mg/mg. The pH response of EXO-GO-CO-γ-PGA showed a maximum cumulative release rate of 56.59% (pH 5.0) and 6.73% (pH 7.4) for MIT at different pH conditions. pH 7.4). In vitro cellular assays showed that EXO-GO-CO-γ-PGA-MIT was more potent in killing MDA-MB-231 cells due to its targeting ability and had a significantly higher pro-apoptotic capacity compared to GO-CO-γ-PGA-MIT. The results showed that this bionic nano-intelligent drug delivery system has good drug slow release function, can increase the local drug concentration of tumor and enhance the pro-apoptotic ability of MIT, so this newly synthesized bionic drug delivery carriers (EXO-GO-CO-γ-PGA-MIT) has potential application in breast cancer treatment.

Author(s):  
Meena K. S. ◽  
Sonia K ◽  
Alamelu Bai S

In order to develop the efficiency and the specificity of anticancer drug delivery, we have designed an innovative nanocarrier. The nanocarrier system comprises of a multifunctional graphene oxide nanoparticle-based drug delivery system (GO-CS-M-DOX) as a novel platform for intracellular drug delivery of doxorubicin (DOX). Firstly, graphene oxide (GO) was synthesized by hummer’s method whose surface was functionalized by chitosan (CS) in order to obtain a more precise drug delivery, the system was then decorated with mannose (M). Further conjugation of an anti-cancer drug doxorubicin to the nanocarrier system resulted in GO-CS-M-DOX drug delivery system. The resultant conjugate was characterized for its physio-chemical properties and its biocompatibility was evaluated via hemolysis assay. The drug entrapment efficiency is as high as 90% and in vitro release studies of DOX under pH 5.3 is significantly higher than that under pH 7.4. The anticancer activity of the synthesized drug delivery system was studied by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay against MCF-7 cell line. These results stated that the pH dependent multifunctional doxorubicin- chitosan functionalized graphene oxide based nanocarrier system, could lead to a promising and potential platform for intracellular delivery and cytotoxicity activity for variety of anticancer drugs.   


Nanomedicine ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. 981-1000
Author(s):  
C Ethan Byrne ◽  
Carlos E Astete ◽  
Manibarathi Vaithiyanathan ◽  
Adam T Melvin ◽  
Mahsa Moradipour ◽  
...  

Aim: Few targeted therapies are available for triple-negative breast cancer (TNBC) patients. Here, we propose a novel alkaline-lignin-conjugated-poly(lactic- co-glycolic acid) (L-PLGA) nanoparticle drug delivery system to improve the efficacy of targeted therapies. Materials & methods: L-PLGA nanoparticles (NPs) loaded with the MEK1/2 inhibitor GDC-0623 were characterized, tested in vitro on MDA-MB-231 TNBC cell line and compared with loaded PLGA NPs. Results: Loaded L-PLGA NPs were less than half the size of PLGA NPs, had slower drug release and improved the efficacy of GDC-0623 when tested in vitro. We demonstrated that GDC-0623 reversed epithelial-to-mesenchymal transition in TNBC. Conclusion: Our findings indicate that L-PLGA NPs are superior to PLGA NPs in delivering GDC-0623 to cancer cells for improved efficacy in vitro.


2021 ◽  
Vol 133 ◽  
pp. 111053
Author(s):  
Dorota Bartusik-Aebisher ◽  
Grzegorz Chrzanowski ◽  
Zuzanna Bober ◽  
David Aebisher

RSC Advances ◽  
2016 ◽  
Vol 6 (72) ◽  
pp. 68134-68140 ◽  
Author(s):  
Fang Ding ◽  
Fanhong Wu ◽  
Qingqing Tian ◽  
Lingling Guo ◽  
Jing Wang ◽  
...  

Graphene oxide has shown great potential in drug delivery.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yi-Zhi Zhu ◽  
Di Xu ◽  
Zhen Liu ◽  
Tian Tian ◽  
Fei Deng ◽  
...  

Triple-negative breast cancer (TNBC) is a highly malignant tumor. At present, there are still no targeted drugs for TNBC. Clinical chemotherapeutic drugs, such as doxorubicin (DOX), have the characteristic of nontargeted distribution in treatment of TNBC, causing severe side effects. Therefore, new target treatment strategies for TNBC are of urgent need. It was speculated that glutamine could be a potential target because it is in high demand by TNBC. In this study, we found that the transporter for glutamine, ASCT2 (solute carrier family 1 member 5 (SLC1A5)), is highly expressed in TNBC by analysis of data from The Cancer Genome Atlas (TCGA) and experiments in vitro. Based on this, glutamine was grafted onto a polymeric drug carrier in order to develop a tumor-targeting drug delivery system for treatment of TNBC. Firstly, pH-responsive glutamine-PEG5000-b-PAE10000 (Gln-PEG-b-PAE) copolymers were synthesized using Fmoc-PEG5000-b-PAE10000 (Fmoc-PEG-b-PAE) copolymers. Then, Gln-PEG-b-PAE@DOX micelles were prepared by loading DOX to Gln-PEG-b-PAE copolymer using a solvent casting technology. In vitro, Gln-PEG-b-PAE@DOX micelles exhibited pH-dependent micellization-decellularization behavior; namely, they can rapidly release DOX in acidic environment of pH 6.0 but release very slowly in physiological condition. Moreover, glutamine competition experiment showed that Gln-PEG-b-PAE@DOX micelles had the ability to target MDA-MB-231 cells. Compared to free DOX, Gln-PEG-b-PAE@DOX micelles had significantly greater cytotoxic effect and antiproliferative activity against MDA-MB-231 cells. In vivo, compared to free DOX and mPEG-b-PAE@DOX micelles, Gln-PEG-b-PAE@DOX micelles significantly inhibited tumor growth in tumor-bearing mice. Therefore, Gln-PEG-b-PAE@DOX micelles, as a tumor-targeting drug delivery system, may provide a new method for the treatment of TNBC.


2021 ◽  
Author(s):  
Reza Davarnejad ◽  
Kiyana Layeghy ◽  
Meysam Soleymani ◽  
Arvin Ayazi

Abstract Quercetin, a natural polyphenolic compound, has attracted much attention due to its great therapeutic potential against various types of diseases. But clinical applications of quercetin are limited due to its poor aqueous solubility and low bioavailability. The main purpose of this research was to evaluate the therapeutic potential of quercetin-loaded Pluronic F127 (PF127)/Tween 80 mixed nanomicelles as a passive targeted drug delivery system for breast cancer therapy. To this end, quercetin-loaded mixed nanomicelles with different mass ratios of drug:PF127:Tween 80 were prepared by the thin-film hydration method. The highest drug loading and entrapment efficiency were obtained to be 2.3% and 98.0%, respectively, for mixed micelles with drug:PF127:Tween 80 ratio of 1:40:15. The physical interactions of quercetin with PF127 and Tween 80 at optimized ratio was investigated by XRD and FTIR analyses. The mean hydrodynamic size and surface charge of prepared nanomicelles, measured by DLS and zeta potential analyses, were 22.1 nm and -7.63 mV, respectively. The results of in-vitro drug release experiments showed that, the mixed micellar system has a prolong and sustained release behavior compared to the solution of free quercetin. Moreover, the in-vitro cytotoxicity studies of quercetin-loaded mixed nanomicelles on breast cancer cells (MCF-7) revealed that, the encapsulated drug have a lower IC50 value (8.9 µg/mL) compared to the free drug (49.2 µg/mL). Our results suggest that, quercetin-loaded mixed nanomicelles can be considered as a promising drug delivery system with prolonged release and potentiated cytotoxicity against breast cancer cells.


2020 ◽  
Author(s):  
Hang Chen ◽  
Sifan Huang ◽  
Heyi Wang ◽  
Xinmei Chen ◽  
Haiyan Zhang ◽  
...  

Abstract Background: Combination of the prodrug technique with an albumin nanodrug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. Results: In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the NabTM technology of paclitaxel palmitate (PTX-PA). Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin NPs (Nab-PTX-PA) remained in the tumor for a longer time post injection. Compared with saline and Abraxane® (nanoparticle albumin-bound (nab)-paclitaxel), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organsand more importantly it inhibited tumor cell proliferation more effectively as compared with commercial Abraxane®.Conclusions: This carrier strategy for small molecule drugs is based on naturally evolved interactions between LCFAs(Long Chain Fatty Acids) and HSA(human serum albumin), demonstrated here for PTX. Nab-PTX-PA shows higher maximum tolerated doses and increased efficacy in vivo in breast cancer models, as compared to Abraxane for FDA-approved clinical formulations. This novel injectable Nab-PTX-PA platform has great potential as an effective drug delivery system in the treatment of breast cancer.


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