Doxorubicin and siRNA Co-Delivery System Based on Carbon Dots Inhibits Chemoresistance of Lung Cancer

Author(s):  
Hui Luo ◽  
Kexin Tang ◽  
Kaichen Huang ◽  
Xi Lin ◽  
Chaoming Mei ◽  
...  

Abstract BackgroundThe resistance to the anti-cancer agent limits the chemotherapy effect in the cancer therapy. Tumor easily develops resistance to anti-cancer drugs leading to decreased therapy efficiency of chemotherapies. Targeting signaling molecules related with chemoresistance through strategy of co-delivery siRNA and chemotherapeutics may overcome the multidrug resistance to chemotherapy. A co-delivery nanosystem that could carry siRNA and DOX simultaneously has been studied in this work. ResultsThe co-delivery is based on carbon dots was surface-modified with poly-ethylenimine (PEI), and loaded the siMRP1 and chemotherapeutics by electronstatic interactions on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI were raw materials and passivator during the reaction process that makes CD exhibit excellent optical property and the capability of loading siRNA. The CD-PEI was capable of loading and delivering siMRP1 and DOX to tumor and release synchronously in cell by pH-triggered manner using flow cytometry and confocal laser scanning microscopy analysis. MRP1 was successfully knocked down by siRNA. The silencing of MRP1 by co-delivery system could increase DOX accumulation and significantly enhance the inhibitory effect of metastatic potential elicited by doxorubicin in A549 and A549/ADM cells.ConclusionThe co-delivery systems effectively loaded and released siRNA and DOX agents to the targeted tumor, overcoming the resistant to chemotherapy. By suppressing MRP1, CD-PEI-DOX-siMRP1 can obviously increase the drug intercellular accumulation and inhibit the cell proliferation, migration and invasion, implying its potential application in enhancing therapeutic efficiency in clinical practices.

2021 ◽  
Author(s):  
Hui Luo ◽  
Kexin Tang ◽  
Kaichen Huang ◽  
Xi Lin ◽  
Chaoming Mei ◽  
...  

Abstract BackgroundThe resistance to the anti-cancer agent limits the chemotherapy effect in the cancer therapy. Tumor easily develops resistance to anti-cancer drugs leading to decreased therapy efficiency of chemotherapies. Targeting signaling molecules related with chemoresistance through strategy of co-delivery siRNA and chemotherapeutics may overcome the multidrug resistance to chemotherapy. A co-delivery nanosystem that could carry siRNA and DOX simultaneously has been studied in this work. ResultsThe co-delivery is based on carbon dots was surface-modified with poly-ethylenimine (PEI), and loaded the siMRP1 and chemotherapeutics by electronstatic interactions on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI were raw materials and passivator during the reaction process that makes CD exhibit excellent optical property and the capability of loading siRNA. The CD-PEI was capable of loading and delivering siMRP1 and DOX to tumor and release synchronously in cell by pH-triggered manner using flow cytometry and confocal laser scanning microscopy analysis. MRP1 was successfully knocked down by siRNA. The silencing of MRP1 by co-delivery system could increase DOX accumulation and significantly enhance the inhibitory effect of metastatic potential elicited by doxorubicin in A549 and A549/ADM cells.ConclusionThe co-delivery systems effectively loaded and released siRNA and DOX agents to the targeted tumor, overcoming the resistant to chemotherapy. By suppressing MRP1, CD-PEI-DOX-siMRP1 can obviously increase the drug intercellular accumulation and inhibit the cell proliferation, migration and invasion, implying its potential application in enhancing therapeutic efficiency in clinical practices.


2020 ◽  
Author(s):  
Hui Luo ◽  
Kaichen Huang ◽  
Kexin Tang ◽  
Xi Lin ◽  
Chaoming Mei ◽  
...  

Abstract BackgroundTumor easily develops resistance to anti-cancer drugs leading to decreased therapy efficiency of chemotherapies. Targeting signaling molecules related with chemoresistance through strategy of co-delivery siRNA and chemotherapeutics may overcome the multidrug resistance to chemotherapy. A co-delivery nanosystem that could carry siRNA and DOX simultaneously has been studied in this work. ResultsThe co-delivery is based on carbon dots was surface-modified with poly-ethylenimine (PEI), and loaded the siMRP1 and chemotherapeutics on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI were raw materials and passivator during the reaction process that makes CD exhibit excellent optical property. The CD-PEI was capable of loading and delivering siMRP1 and DOX to tumor and release synchronously in cell by acid-triggered manner, i.e. hydrazone bond cleavage and endosome/lysosome escape using flow cytometry and confocal laser scanning microscopy analysis. MRP1 was successfully knocked down by siRNA. The silencing of MRP1 by co-delivery system could increase DOX accumulation and significantly enhance the inhibitory effect of metastatic potential elicited by doxorubicin in A549 and A549/ADM cells.ConclusionThe co-delivery systems effectively loaded and released siRNA and DOX agents to the targeted lung tumor, overcoming the resistant to chemotherapy. By suppressing MRP1, CD-PEI-DOX-siMRP1 can obviously increase the drug intercellular accumulation and inhibit the cell proliferation, migration and invasion, implying its potential application in enhancing therapeutic efficiency in clinical practices.


2021 ◽  
Author(s):  
Luo Hui ◽  
Tang Kexin ◽  
Lin Xi ◽  
Huang Yongquan ◽  
Yu Ting ◽  
...  

Abstract BackgroundAcquired resistance against chemotherapeutic drugs hinders the clinical efficacy of treatments in lung cancer. To circumvent the developed resistance, we aim to target critical signaling molecules related with chemoresistance through co-delivering siRNA and chemotherapeutics. The co-delivery strategy may address the unmet need to efficiently counteracting the multidrug resistance in treating lung cancer. MethodsA co-delivery nanosystem that could carry siRNA and DOX simultaneously has been studied in this work. The co-delivery is based on carbon dots was surface-modified with poly-ethylenimine (PEI), and loaded the siMRP1 and chemotherapeutics on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI were raw materials and passivator during the reaction process that makes CD exhibit excellent optical property.ResultsThe CD-PEI was capable of loading and delivering siMRP1 and DOX to tumor and release synchronously in cells by acid-triggered manner.The expression of MRP1 in A549 and A549/ADM cells were successfully knocked down by siRNA. The silencing of MRP1 by co-delivery system could increase DOX accumulation and significantly enhance the inhibitory effect of cell viability. Moreover, the co-delivery system enhances the inhibitory effect of metastatic potential elicited by doxorubicin in A549 and A549/ADM cells.ConclusionBy suppressing MRP1, the co-delivery system can obviously increase the drug cellular accumulation and inhibit the cell proliferation, migration and invasion of lung cancer, implying its potential application to overcome chemoresistance and enhance therapeutic efficiency in clinical practices.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Kai Zhang ◽  
Tao Peng ◽  
Qingying Yan ◽  
Leitao Sun ◽  
Haojun Miao ◽  
...  

Jiedu Sangen Decoction (JSD), a traditional Chinese medicine (TCM) formula, has been widely used in China to treat gastrointestinal cancer, especially as an adjuvant therapy in colorectal cancer (CRC) patients. This study aimed to evaluate the efficacy of JSD and Jiedu Sangen aqueous extract (JSAE) in colon cancer cells and explored the underlining mechanisms by cytotoxicity assay, scratch assay, transwell migration assay, matrigel invasion assay, confocal laser scanning microscopy, and western blot analysis. We demonstrated that JSAE inhibited the growth of colon cancer SW480 cells in a dose-dependent manner and JSAE repressed cancer cell migration and invasion. Furthermore, epithelial mesenchymal transition (EMT) was reversed by JSAE via enhancing E-cadherin expression and attenuating protein levels of EMT promoting factors such as N-cadherin, Slug, and ZEB1. These findings provided the first experimental evidence confirming the efficacy of JSAE in repressing invasion and metastasis of CRC and paving a way for the broader use of JSD in clinic.


2009 ◽  
Vol 79 (2) ◽  
pp. 353-360 ◽  
Author(s):  
Seung-Pyo Lee ◽  
Shin-Jae Lee ◽  
Bum-Soon Lim ◽  
Sug-Joon Ahn

AbstractObjective: To test the hypothesis that there are no significant differences in the adhesion of mutans streptococci (MS) to various orthodontic materials based on their surface characteristics.Materials and Methods: Surface roughness (SR) and surface free energy (SFE) characteristics were investigated for nine different orthodontic materials (four orthodontic adhesives, three bracket raw materials, hydroxyapatite blocks, and bovine incisors) using confocal laser scanning microscopy and sessile drop method. Each material, except the bovine incisors, was incubated with whole saliva or phosphate-buffered saline for 2 hours. Adhesion assays were performed by incubating tritium-labeled MS with each material for 3 or 6 hours.Results: Orthodontic adhesives had higher SFE characteristics and lower SR than bracket materials. Orthodontic adhesives showed a higher MS retaining capacity than bracket materials, and MS adhesion to resin-modified glass ionomer and hydroxyapatite was highest. Extended incubation time increased MS adhesion, while saliva coating did not significantly influence MS adhesion. SFE, specifically its dispersive and polar components, was positively correlated with MS adhesion, irrespective of saliva coating.Conclusions: The hypothesis is rejected. This study suggests that SFE characteristics play an important role in the initial MS adhesion to orthodontic materials.


Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 180 ◽  
Author(s):  
Jin Ah Kim ◽  
Dong Youl Yoon ◽  
Jin-Chul Kim

Since cancer cells are oxidative in nature, anti-cancer agents can be delivered to cancer cells specifically without causing severe normal cell toxicity if the drug carriers are designed to be sensitive to the intrinsic characteristic. Oxidation-sensitive liposomes were developed by stabilizing dioleoylphosphatidyl ethanolamine (DOPE) bilayers with folate-conjugated poly(hydroxyethyl acrylate-co-allyl methyl sulfide) (F-P(HEA-AMS)). The copolymer, synthesized by a free radical polymerization, was surface-active but lost its surface activity after AMS unit was oxidized by H2O2 treatment. The liposomes with F-P(HEA-AMS) were sensitive to H2O2 concentration (0%, 0.5%, 1.0%, and 2.0%) in terms of release, possibly because the copolymer lost its surface activity and its bilayer-stabilizing ability upon oxidation. Fluorescence-activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM) revealed that doxorubicin (DOX)-loaded liposomes stabilized with folate-conjugated copolymers markedly promoted the transport of the anti-cancer drug to cancer cells. This was possible because the liposomes were readily translocated into the cancer cells via receptor-mediated endocytosis. This liposome would be applicable to the delivery carrier of anticancer drugs.


Nano LIFE ◽  
2020 ◽  
Vol 10 (04) ◽  
pp. 2040013 ◽  
Author(s):  
Rong Liang ◽  
Yuxuan Wang ◽  
Lina Wu ◽  
Xinjiong Ni ◽  
Cheng Yang

Nanostructured lipid carrier (NLC) is a new colloidal delivery system which can effectively solve the problems of stability and transdermal delivery of active ingredients with poor water solubility and biocompatibility. Coenzyme Q10 (CoQ10), as a lipophilic antioxidant, has poor chemical stability due to unsaturated double bonds in its molecular structure, which limits its addition and application in cosmetics. In this study, CoQ10 NLC was prepared using the mixture of Caprylyl/Capryl Glycoside (APG) and quaternized chitosan (QCS). The particle size of the QCS–APG–NLC was around 250 nm. Compared to NLC stabilized by APG, QCS–APG–NLC has better storage stability under high temperature and light conditions. In vitro transdermal experiment analysis and confocal laser scanning microscopy (CLSM) observation found that QCS modification can effectively increase the penetration amount of CoQ10 in the skin. So, it is suggested that QCS modified APG–NLC can be used as an effective transdermal delivery system for lipophilic active components.


Nanomedicine ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. 677-689 ◽  
Author(s):  
Xiaoming Zhao ◽  
Tianyang Qi ◽  
Mingxi Yang ◽  
Wenjing Zhang ◽  
Chenfei Kong ◽  
...  

Aim: Procaine-derived carbon dots, termed P-dots, expectedly offer both fluorescent biomarker function and anticancer activity. Materials & methods: P-dots were synthesized by condensing procaine, citric acid and ethylenediamine via hydrothermal synthesis and characterized by transmission electron microscopy, Fourier transform infrared spectroscopy and x-ray photoelectron spectroscopy. The cellular uptake behavior and the bioimaging performance of P-dots were assessed by confocal laser scanning microscopy. Their antitumor activity was evaluated using the CCK-8 assays and in vivo antitumor experiments, and the underlying mechanism was evaluated by flow cytometry and western blotting. Results: P-dots exhibited excellent luminescence properties suitable for bioimaging and considerable anticancer activity associated with caspase-3-related cell apoptosis. Conclusion: The synthesized procaine-derived carbon dots presented a dual function consisting of bioimaging and anticancer activity, which may enable their implementation as safe and effective clinical nanotherapeutics.


Nanomaterials ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 706 ◽  
Author(s):  
Yuefang Niu ◽  
Guo Ling ◽  
Li Wang ◽  
Shanyue Guan ◽  
Zheng Xie ◽  
...  

Emphasis using phototheranostics has been placed on the construction of multifunctional nanoplatforms for simultaneous tumor diagnosis and therapy. Herein, we put forth a novel nanosized luminescent material using the incorporation of red emissive carbon dots on gold nanorods through polyethylene glycol as a covalent linkage for dual-modal imaging and photothermal therapy. The novel nanohybrids, not only retain the optical properties of the gold nanorod and carbon dots, but also possess superior imaging performance in both confocal laser scanning microscopy and fluorescence lifetime imaging microscopy. The nanohybrids also exhibit excellent photothermal performance as phototheranostic nanohybrid probes for in vitro assays. This study promises a new multifunctional nanoplatform for cancer diagnostics and therapeutics.


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