scholarly journals Enhanced antitumor efficacy on colon cancer using EGF functionalized PLGA nanoparticles loaded with 5-Fluorouracil and perfluorocarbon

2019 ◽  
Author(s):  
pingping Wu ◽  
Qing Zhou ◽  
Huayun Zhu ◽  
Yan Zhuang ◽  
Jun Bao

Abstract Background: Recurrence and metastasis are the shortcomings of the clinical treatment of colon cancer. Finding an efficacy strategy for the treatment of colon cancer is important. In recent years, poly lactic-co-glycolic acid (PLGA) has been shown to have potential as a broad therapeutic drug delivery system. This study aimed to design a dual-loaded nanoparticles drug delivery system to overcome the limitations of chemotherapeutic drugs in colon cancer therapy. Methods: We developed epidermal growth factor (EGF) functionalized poly PLGA nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perfluorocarbon (PFC) (EGF-PLGA@5Fu/PFC NPs) for target therapy of colon cancer. EGF-PLGA@5Fu /PFC NPs were estimated by morphology, size distribution, in vitro stability and release profile. CCK-8, Hoechst33342 staining and flow cytometry assays were performed to investigate the functions of EGF-PLGA@5Fu/PFC NPs in SW620 cells. Results: We found that EGF-PLGA@5Fu/PFC NPs had an average size of 200 nm with a 5Fu-loading efficiency of 7.29%. Targeted EGF-PLGA@5Fu/PFC NPs exhibited higher cellular uptake than non-targeted NPs in colon cancer cells. EGF-PLGA@5Fu/PFC NPs were found to have the best efficiency on cell viability suppression and apoptosis induction in SW620 colon cancer cells. In xenograft mice, EGF-PLGA@5Fu/PFC NPs had the best suppressive effects on tumor growth compared with 5Fu, PLGA@5Fu and PLGA@5Fu/PFC NPs. The results of histopathological analysis further indicated that EGF-targeted NPs were the most efficient on tumor growth inhibition. Mechanically, the data demonstrated the improved therapeutic outcomes were owing to the fact that PFC relieved tumor hypoxia via transporting oxygen to the tumor. Conclusions: We creatively constructed a biocompatible nanodrug delivery system and functionalized nanoparticles might provide new potential for selective delivery of chemotherapy drugs to cancers.

2020 ◽  
Author(s):  
Pingping Wu(Former Corresponding Author) ◽  
Qing Zhou ◽  
Huayun Zhu ◽  
Yan Zhuang ◽  
Jun Bao(New Corresponding Author)

Abstract Background: Recurrence and metastasis are the shortcomings of the clinical treatment of colon cancer. Finding an efficacy strategy for the treatment of colon cancer is important. In recent years, poly lactic-co-glycolic acid (PLGA) has been shown to have potential as a broad therapeutic drug delivery system. This study aimed to design a dual-loaded nanoparticles drug delivery system to overcome the limitations of chemotherapeutic drugs in colon cancer therapy. Methods: We developed epidermal growth factor (EGF) functionalized poly PLGA nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perfluorocarbon (PFC) (EGF-PLGA@5Fu/PFC NPs) for target therapy of colon cancer. EGF-PLGA@5Fu /PFC NPs were estimated by morphology, size distribution, in vitro stability and release profile. CCK-8, Hoechst33342 staining and flow cytometry assays were performed to investigate the functions of EGF-PLGA@5Fu/PFC NPs in SW620 cells. Results: We found that EGF-PLGA@5Fu/PFC NPs had an average size of 200 nm with a 5Fu-loading efficiency of 7.29%. Targeted EGF-PLGA@5Fu/PFC NPs exhibited higher cellular uptake than non-targeted NPs in colon cancer cells. EGF-PLGA@5Fu/PFC NPs were found to have the best efficiency on cell viability suppression and apoptosis induction in SW620 colon cancer cells. In xenograft mice, EGF-PLGA@5Fu/PFC NPs had the best suppressive effects on tumor growth compared with 5Fu, PLGA@5Fu and PLGA@5Fu/PFC NPs. The results of histopathological analysis further indicated that EGF-targeted NPs were the most efficient on tumor growth inhibition. Mechanically, the data demonstrated the improved therapeutic outcomes were owing to the fact that PFC relieved tumor hypoxia via transporting oxygen to the tumor. Conclusions: We creatively constructed a biocompatible nanodrug delivery system and functionalized nanoparticles might provide new potential for selective delivery of chemotherapy drugs to cancers.


2019 ◽  
Author(s):  
Pingping Wu ◽  
Qing Zhou ◽  
Huayun Zhu ◽  
Yan Zhuang ◽  
Jun Bao

Abstract Recurrence and metastasis are the shortcomings of the clinical treatment of colon cancer. Finding an efficacy strategy for the treatment of colon cancer is important. In recent years, PLGA has been shown to have potential as a broad therapeutic drug delivery system. this study aimed to design a dual-loaded nanoparticles drug delivery system to overcome the limitations of chemotherapeutic drugs in colon cancer therapy. We developed epidermal growth factor (EGF) functionalized poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perfluorocarbon (PFC) (EGF-PLGA@5Fu/PFC) for target therapy of colon cancer. EGF-PLGA@5Fu /PFC NPs were estimated to have an average size of 200 nm with a 5Fu-loading efficiency of 7.29%. In vitro release profile exhibited a pH-responsive release. CCK-8, Hoechst33342 staining and flow cytometry assays were performed to investigate the functions of EGF-PLGA@5Fu/PFC NPs in SW620 cells. Targeted EGF-PLGA@5Fu/PFC NPs also exhibited higher cellular uptake than non-targeted NPs in colon cancer cells. EGF-PLGA@5Fu/PFC NPs were found to have the best efficiency on cell viability suppression and apoptosis induction in SW620 cells. In xenograft mice, EGF-PLGA@5Fu/PFC NPs had the best suppressive effects on tumor growth compared with 5Fu, PLGA@5Fu and PLGA@5Fu/PFC NPs. The results of histopathological analysis further indicated that EGF-targeted NPs were the most efficient on tumor growth inhibition. Mechanically, the data demonstrated the improved therapeutic outcomes were owing to the fact that PFC could relieve tumor hypoxia via transporting oxygen to the tumor. We creatively constructed a biocompatible nanodrug delivery system and functionalized nanoparticles may provide new potential for selective delivery of chemotherapy drugs to cancers.


2020 ◽  
Author(s):  
pingping Wu ◽  
Qing Zhou ◽  
Huayun Zhu ◽  
Yan Zhuang ◽  
Jun Bao

Abstract Background: Tumor recurrence and metastasis occur at a high rate in patients with colon cancer. Identification of effective strategies for the treatment of colon cancer is critical. Recently, poly (lactic-co-glycolic acid) (PLGA) has been shown to have potential as a broad therapeutic drug delivery system. We designed a dual-loaded nanoparticle drug delivery system to overcome the limitations of chemotherapeutic drugs used to treat colon cancer. Methods: We developed epidermal growth factor (EGF) functionalized PLGA nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perfluorocarbon (PFC) (EGF-PLGA@5Fu/PFC) for targeted treatment of colon cancer. CCK-8 assay, Hoechst33342 staining and flow cytometry were performed to investigate the functions of EGF-PLGA@5Fu/PFC NPs in SW620 cells. Beside, animal experiment, histological analysis and immunofluorescence staining were adopted to further confirm the role of EGF-PLGA@5Fu/PFC NPs in vivo. Results: The findings showed that EGF-PLGA@5Fu /PFC NPs had an average size 200 nm and a 5Fu-loading efficiency of 7.29%. Furthermore, in vitro release was pH-sensitive. Targeted EGF-PLGA@5Fu/PFC NPs exhibited higher cellular uptake than non-targeted NPs into colon cancer cells. In addition, EGF-PLGA@5Fu/PFC NPs suppressed cell viability and induced apoptosis in SW620 cells to a greater extent than non-targeted NPs. In tumor xenografted mice, EGF-PLGA@5Fu/PFC NPs suppressed tumor growth more effectively than 5Fu, PLGA@5Fu or PLGA@5Fu/PFC NPs. Histopathological analysis further demonstrated that EGF-targeted NPs inhibited tumor growth to a greater extent than non-targeted or non-NP treatments. The improved therapeutic outcomes observed in this study were due to relief of tumor hypoxia by transport of oxygen by PFC to the tumors. Conclusion: We constructed a biocompatible nanodrug delivery system based on functionalized nanoparticles that provided a novel strategy for selective delivery of chemotherapy drugs to tumors.


2009 ◽  
Vol 3 (2) ◽  
Author(s):  
A. Garg ◽  
A. W. Tisdale ◽  
E. Kokkoli

The ability to target cancer cells using an appropriate drug delivery system can significantly reduce the associated side effects from cancer therapies and can help in improving overall quality of life post cancer survival. Integrin α5β1 is expressed on several types of cancer cells, including colon cancer, and plays an important role in tumor growth and metastasis. Thus, the ability to target the integrin α5β1 using an appropriate drug delivery nano-vector can signficantly help in inhibiting tumor growth and reducing tumor metastasis. In this study we have designed functionalized stealth liposomes (liposomes covered with polyethylene glycol (PEG)) that specifically target the integrin α5β1. The PEG provides a steric barrier allowing the liposomes to circulate in the blood for longer duration and the functionalizing moiety, the PR_b peptide specifically recognizes and binds to integrin α5β1 expressing cells. PR_b is a novel peptide sequence, designed in our lab, that mimics the cell adhesion domain of fibronectin, and includes four building blocks, RGDSP (the primary recognition site for α5β1), PHSRN (the synergy site for α5β1), a (SG)5 linker, and a KSS spacer. In this study, we demonstrate that by optimizing the amount of PEG and PR_b on the liposomal interface we can engineer nano-vectors that bind to CT26.WT, HCT116, and RKO colon cancer cells in a specific manner and are internalized through α5β1-mediated endocytosis. Stealth liposomes functionalized with an RGD containing peptide bind to colon cancer cells and internalize, but they have much lesser efficiency than PR_b-targeted stealth liposomes, and more importantly they are not as specific since many integrins bind to RGD. PR_b-targeted stealth liposomes are as cytotoxic as free 5-Fluorouracil (5-FU) and exert the highest cytotoxicity on CT26.WT cells compared to RGD-targeted stealth liposomes and non-targeted stealth liposomes. In order to further increase the efficacy of the system we have designed peptide-functionalized stealth liposomes that are pH-sensitive and exhibit triggered release under mild acidic conditions present in endocytotic vesicles. The proposed targeted delivery system has the great potential to deliver a therapeutic load directly to colon cancer cells, in an efficient and specific manner.


2016 ◽  
Vol 76 (24) ◽  
pp. 7208-7218 ◽  
Author(s):  
Mingzhen Zhang ◽  
Changlong Xu ◽  
Liuqing Wen ◽  
Moon Kwon Han ◽  
Bo Xiao ◽  
...  

2020 ◽  
Vol 8 (6) ◽  
pp. 1592-1603
Author(s):  
Zachary Shaw ◽  
Arth Patel ◽  
Thai Butcher ◽  
Tuhina Banerjee ◽  
Ren Bean ◽  
...  

New aliphatic pseudo-branched polyester copolymers are synthesized from diethylmalonate. The formulated nanomedicine successfully encapsulates therapeutic drug in higher dosage and deliver specifically to cancer cells for diagnosis and treatment.


RSC Advances ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 2656-2663
Author(s):  
Boye Zhang ◽  
Qianqian Duan ◽  
Yi Li ◽  
Jianming Wang ◽  
Wendong Zhang ◽  
...  

The system is pH-responsive and redox-controlled release. And the charge reversal and size transitions of the system can enhance the targeted ability. Moreover, the system can recognize the cancer cells by the fluorescence imaging.


Oncogene ◽  
2004 ◽  
Vol 23 (1) ◽  
pp. 58-70 ◽  
Author(s):  
Kenichi Yoshida ◽  
Naoki Oyaizu ◽  
Anindya Dutta ◽  
Ituro Inoue

2015 ◽  
Vol 12 (5) ◽  
pp. 1422-1430 ◽  
Author(s):  
Masaharu Murata ◽  
Sayoko Narahara ◽  
Takahito Kawano ◽  
Nobuhito Hamano ◽  
Jing Shu Piao ◽  
...  

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