Hypoxia-Induced Resistance to Chemotherapy in Cancer

Minassian, Lori M.; Cotechini, Tiziana; Huitema, Erin; Graham, Charles H.

doi:10.1007/978-3-030-12734-3_9

Cited by 67 publications

(65 citation statements)

References 166 publications

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“…A self-assembled nanosystem co-loaded with trichosanthin (TCS) protein and albendazole (ABZ) exhibited excellent antitumor effects through reduction of multidrug resistance [26]. Previous studies have shown that tumor hypoxia can induce chemotherapy resistance [27]. PFC, commonly used as oxygen carriers in clinical use, has been reported to promote oxygen delivery to tumor microenvironments [28].…”

Section: Discussionmentioning

confidence: 99%

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

Wu¹,

Zhou²,

Zhu³

et al. 2020

Preprint

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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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Wu¹,

Zhou²,

Zhu³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…A self-assembled nanosystem co-loaded with trichosanthin (TCS) protein and albendazole (ABZ) exhibited great antitumor effect through overcoming multidrug resistance [26]. It is well established that tumor hypoxia could cause chemotherapy resistance [27]. PFC, commonly applied as oxygen carrier in clinical use, has been reported to have the capability of delivering oxygen to tumor environments [28].…”

Section: Discussionmentioning

confidence: 99%

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

Wu¹,

Zhou²,

Zhu³

et al. 2019

Preprint

View full text Add to dashboard Cite

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.

show abstract

“…A self-assembled nanosystem co-loaded with trichosanthin (TCS) protein and albendazole (ABZ) exhibited great antitumor effect through overcoming multidrug resistance [27]. It is well established that tumor hypoxia caused chemotherapy resistance [28]. PFC, commonly applied as oxygen carrier in clinical use, has been reported to have the capability of delivering oxygen to tumor environments [29].…”

Section: Discussionmentioning

confidence: 99%

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

Wu¹,

Zhou²,

Zhu³

et al. 2019

Preprint

View full text Add to dashboard Cite

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.

show abstract

Hypoxia-Induced Resistance to Chemotherapy in Cancer

Cited by 67 publications

References 166 publications

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

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

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

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

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