scholarly journals Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors

2018 ◽  
Vol 50 (1) ◽  
pp. 79-91 ◽  
Author(s):  
Wei Yan ◽  
Mingyue Tao ◽  
Baofei Jiang ◽  
Mengchu Yao ◽  
Yali Jun ◽  
...  

Background/Aims: Multidrug resistance (MDR) is the most common cause of chemotherapy failure. Upregulation of P-glycoprotein (P-gp) is one of the main mechanisms underlying MDR. Methods: In this study, we developed a targeted drug and small interfering (si)RNA co-delivery system based on specific aptamer-conjugated grapefruit-derived nanovectors (GNVs) that we tested in MDR LoVo colon cancer cells. The internalization of nanovectors in cancer cells was tested by fluorescence microscopy and flow cytometry. The anti-cancer activity in vitro was determined by colony formation and cell apoptosis assays. The biodistribution of nanovectors was analyzed by live imaging and the anti-cancer activity in vivo was observed. Results: GNVs loaded with aptamer increased doxorubicin (Dox) accumulation in MDR LoVo cells, an effect that was abolished by pretreatment with DNase. The LA1 aptamer effectively promoted nanovector internalization into cells at 4°C and increased the targeted delivery of Dox to tumors. Constructs harboring Dox, LA1, and P-gp siRNA more effectively inhibited proliferation and enhanced apoptosis in cultured MDR LoVo cells while exhibiting more potent anti-tumor activity in vivo than free Dox or GNVs loaded with Dox alone or in conjunction with LA1, an effect that was associated with downregulation of P-gp expression. Conclusion: This GNV-based system may be an effective strategy for overcoming MDR in clinical settings.

2018 ◽  
Vol 19 (3) ◽  
pp. 903 ◽  
Author(s):  
Se Byeon ◽  
Young-Su Yi ◽  
Jongsung Lee ◽  
Woo Yang ◽  
Ji Kim ◽  
...  

2011 ◽  
Vol 46 (10) ◽  
pp. 4957-4963 ◽  
Author(s):  
Engin Ulukaya ◽  
Ferda Ari ◽  
Konstantinos Dimas ◽  
Elif Ilkay Ikitimur ◽  
Emel Guney ◽  
...  

2019 ◽  
Vol 110 ◽  
pp. 254-264 ◽  
Author(s):  
Moniba Sajid ◽  
Chao Yan ◽  
Dawei Li ◽  
Siva Bharath Merugu ◽  
Hema Negi ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
pp. 8-15
Author(s):  
Ainaz Mihanfar ◽  
Niloufar Targhazeh ◽  
Shirin Sadighparvar ◽  
Saber Ghazizadeh Darband ◽  
Maryam Majidinia ◽  
...  

Abstract Doxorubicin (DOX) is an effective chemotherapeutic agent used for the treatment of various types of cancer. However, its poor solubility, undesirable side effects, and short half-life have remained a challenge. We used a formulation based on graphene oxide as an anticancer drug delivery system for DOX in MCF-7 breast cancer cells, to address these issues. In vitro release studies confirmed that the synthesized formulation has an improved release profile in acidic conditions (similar to the tumor microenvironment). Further in vitro studies, including MTT, uptake, and apoptosis assays were performed. The toxic effects of the nanocarrier on the kidney, heart and liver of healthy rats were also evaluated. We observed that the DOX-loaded carrier improved the cytotoxic effect of DOX on the breast cell line compared to free DOX. In summary, our results introduce the DOX-loaded carrier as a potential platform for in vitro targeting of cancer cells and suggest further studies are necessary to investigate its in vivo anti-cancer potential.


Author(s):  
Domenico Mattoscio ◽  
Elisa Isopi ◽  
Alessia Lamolinara ◽  
Sara Patruno ◽  
Alessandro Medda ◽  
...  

Abstract Background Innovative therapies to target tumor-associated neutrophils (PMN) are of clinical interest, since these cells are centrally involved in cancer inflammation and tumor progression. Resolvin D1 (RvD1) is a lipid autacoid that promotes resolution of inflammation by regulating the activity of distinct immune and non-immune cells. Here, using human papilloma virus (HPV) tumorigenesis as a model, we investigated whether RvD1 modulates PMN to reduce tumor progression. Methods Growth-curve assays with multiple cell lines and in vivo grafting of two distinct HPV-positive cells in syngeneic mice were used to determine if RvD1 reduced cancer growth. To investigate if and how RvD1 modulates PMN activities, RNA sequencing and multiplex cytokine ELISA of human PMN in co-culture with HPV-positive cells, coupled with pharmacological depletion of PMN in vivo, were performed. The mouse intratumoral immune cell composition was evaluated through FACS analysis. Growth-curve assays and in vivo pharmacological depletion were used to evaluate anti-tumor activities of human and mouse monocytes, respectively. Bioinformatic analysis of The Cancer Genome Atlas (TCGA) database was exploited to validate experimental findings in patients. Results RvD1 decreased in vitro and in vivo proliferation of human and mouse HPV-positive cancer cells through stimulation of PMN anti-tumor activities. In addition, RvD1 stimulated a PMN-dependent recruitment of classical monocytes as key determinant to reduce tumor growth in vivo. In human in vitro systems, exposure of PMN to RvD1 increased the production of the monocyte chemoattractant protein-1 (MCP-1), and enhanced transmigration of classical monocytes, with potent anti-tumor actions, toward HPV-positive cancer cells. Consistently, mining of immune cells infiltration levels in cervical cancer patients from the TCGA database evidenced an enhanced immune reaction and better clinical outcomes in patients with higher intratumoral monocytes as compared to patients with higher PMN infiltration. Conclusions RvD1 reduces cancer growth by activating PMN anti-cancer activities and encouraging a protective PMN-dependent recruitment of anti-tumor monocytes. These findings demonstrate efficacy of RvD1 as an innovative therapeutic able to stimulate PMN reprogramming to an anti-cancer phenotype that restrains tumor growth.


RSC Advances ◽  
2017 ◽  
Vol 7 (6) ◽  
pp. 3408-3412 ◽  
Author(s):  
Long Ma ◽  
Haiyan Liu ◽  
Lingpei Meng ◽  
Ping Qin ◽  
Botao Zhang ◽  
...  

Triterpenoidal saponins fraction isolated from a traditional Chinese medicine Conyza blinii H. Lév. demonstrates anti-cancer activity both in vitro and in vivo.


Oncotarget ◽  
2017 ◽  
Vol 8 (50) ◽  
pp. 87379-87389 ◽  
Author(s):  
Mancang Gu ◽  
Reiko Nishihara ◽  
Yang Chen ◽  
Wanwan Li ◽  
Yan Shi ◽  
...  

2013 ◽  
Vol 144 (5) ◽  
pp. S-166-S-167
Author(s):  
Karen Boland ◽  
Caoimhin Concannon ◽  
Niamh McCawley ◽  
Elaine W. Kay ◽  
Deborah McNamara ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document