Co-delivery of a RanGTP inhibitory peptide and doxorubicin using dual-loaded liposomal carriers to combat chemotherapeutic resistance in breast cancer cells

Haggag, Yusuf A.; Ras, Bayan Abu; El-Tanani, Yahia; Tambuwala, Murtaza M.; McCarron, Paul A.; Isreb, Mohammed; El‐Tanani, Mohamed

doi:10.1080/17425247.2020.1813714

Cited by 45 publications

(33 citation statements)

References 58 publications

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“…Riahi et al identified a novel mutation in RCC1 as a breast cancer susceptibility allele through exome sequencing that has exclusively been found in Tunisian breast cancer patients [ 23 ]. In fact, RCC1 blockade is being investigated as a potential therapeutic strategy against aggressive breast tumors [ 24 ]. Haggag et al showed that liposome-mediated codelivery with Ran-RCC1 inhibitory peptide could improve the antitumor effect of doxorubicin in tumor-bearing mice [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…In fact, RCC1 blockade is being investigated as a potential therapeutic strategy against aggressive breast tumors [ 24 ]. Haggag et al showed that liposome-mediated codelivery with Ran-RCC1 inhibitory peptide could improve the antitumor effect of doxorubicin in tumor-bearing mice [ 24 ]. A previous study found that downregulation of RCC1 could sensitize immunotherapy by upregulating PD-L1 via the p27kip1/CDK4 pathway in non-small cell lung cancer, and the expression of RCC1 was inversely related to the amount of immune cell infiltration [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

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RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases

Deng¹,

Lan²,

Zhao³

et al. 2021

Pathol. Oncol. Res.

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Introduction: Regulator of chromatin condensation 1 (RCC1) is a major guanine-nucleotide exchange factor for Ran GTPase, and it plays key roles in various biological processes. Previous studies have found that RCC1 may play a role in the development of tumors, but little is known about the relationship between RCC1 and colorectal liver oligometastases (CLOs).Methods: One hundred and twenty-nine pairs of matched human CLO samples, including both primary tumor and its liver metastasis specimens, were subjected to immunohistochemistry to determine the location and expression levels of RCC1. Associations between RCC1 and survival as well as gene expression profiling were explored.Results: In this study, we first observed that RCC1 was mildly increased in CLO tumor tissues compared with normal tissues, and the localization was primarily nuclear. In addition, our study found that high RCC1 expression in liver oligometastases was an independent prognostic marker for unfavorable recurrence-free survival and overall survival (p = 0.036 and p = 0.016). Gene expression profiles generated from microarray analysis showed that RCC1 was involved in pathways including “Myc targets,” “E2F targets” and “DNA repair” pathways.Conclusion: Our data indicated that RCC1 was expressed mainly in the nucleus, and strong and significant associations were found between RCC1 expression levels and the survival of CLO patients. These findings indicated that RCC1 may play a role in CLO development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases

Deng¹,

Lan²,

Zhao³

et al. 2021

Pathol. Oncol. Res.

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“…In addition, the antitumor performance of IPLD was better than that of the combination of DOX with anti-PD-L1 antibody (αPD-L1) against subcutaneous (s.c.) CT26 tumors in BALB/c mice without apparent adverse effects. and genes, for combination administration to improve the therapeutic efficacy [58]. Therefore, liposomes play a vital role in anticancer targeted drug delivery and are of great research and clinical interest (Figure 2).…”

Section: Encapsulation Of Small Molecule Drugs With Liposomementioning

confidence: 99%

“…This kind of liposome can respond to specific stimuli, either external stimuli such as light, temperature, ultrasound and magnetism, or internal stimuli such as pH, enzyme and redox [ 56 , 57 ]. Additionally, liposomes can co-load multiple drugs with different structures, ranging from small molecules to macromolecules such as proteins and genes, for combination administration to improve the therapeutic efficacy [ 58 ]. Therefore, liposomes play a vital role in anticancer targeted drug delivery and are of great research and clinical interest ( Figure 2 ).…”

Section: Liposomementioning

confidence: 99%

Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery

Tang

Zhao

et al. 2021

Pharmaceutics

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The encapsulation of therapeutic agents into nano-based drug delivery system for cancer treatment has received considerable attention in recent years. Advancements in nanotechnology provide an opportunity for efficient delivery of anticancer drugs. The unique properties of nanoparticles not only allow cancer-specific drug delivery by inherent passive targeting phenomena and adopting active targeting strategies, but also improve the pharmacokinetics and bioavailability of the loaded drugs, leading to enhanced therapeutic efficacy and safety compared to conventional treatment modalities. Small molecule drugs are the most widely used anticancer agents at present, while biological macromolecules, such as therapeutic antibodies, peptides and genes, have gained increasing attention. Therefore, this review focuses on the recent achievements of novel nano-encapsulation in targeted drug delivery. A comprehensive introduction of intelligent delivery strategies based on various nanocarriers to encapsulate small molecule chemotherapeutic drugs and biological macromolecule drugs in cancer treatment will also be highlighted.

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“…Co-administration of RAN-IP was used to improve the sensitivity of DOX within breast cancer cell lines. 15 The use of RNA interference (RNAi) technology used to reverse multidrug resistance is a powerful treatment for reducing MDR gene expression. 16,17 siMDR1 can be combined with protease to form the RNA-induced silencing complex (RISC).…”

Section: Introductionmentioning

confidence: 99%

Cetuximab-Modified Human Serum Albumin Nanoparticles Co-Loaded with Doxorubicin and MDR1 siRNA for the Treatment of Drug-Resistant Breast Tumors

Yang¹,

Wang²,

Chen³

et al. 2021

IJN

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Background: Breast cancer is the most prevalent cancer among women. Doxorubicin (DOX) is a common chemotherapeutic drug used to treat many different cancers. However, multidrug resistance limits the treatment of breast cancer. MDR1 siRNA (siMDR1) combinatorial therapy has attracted significant attention as a breakthrough therapy for multidrug resistance in tumors. However, naked siRNA is easily degraded by enzymatic hydrolysis requiring an siRNA carrier for its protection. Human serum albumin (HSA) was selected as the carrier due to its excellent biocompatibility, non-toxicity, and non-immunogenicity. Cetuximab was used to modify the HSA nanoparticles in order to target the tumor tissues. Methods:This study used a central composite design response surface methodology (CCD-RSM) to investigate the optimal formula for HSA NPs preparation. Cex-HSA/DOX/MDR1 siRNA (C-H/D/M) was characterized by dynamic light scattering and transmission electron microscopy. The efficacy of C-H/D/M tumor growth inhibitory activity was investigated in vitro and in vivo using confocal imaging, MTT assay, and an MCF-7/ADR tumor-bearing mice model. RT-qPCR, ELISA analysis, and flow cytometry were used to investigate the in vitro antitumor mechanisms of C-H/D/M. Results: The diameter and PDI of the C-H/D/M were 173.57 ± 1.30 nm and 0.027 ± 0.004, respectively. C-H/D/M promoted and maintained the sustained release and the uptake of DOX significantly. After transfection, the MDR1 mRNA and P-gp expression levels were down-regulated by 44.31 ± 3.6% (P < 0.01) and 38.08 ± 2.4% (P < 0.01) in an MCF-7/ADR cell line. The fluorescent images of the treated BALB/c nude mice revealed that C-H/D/M achieved targeted delivery of siMDR1 and DOX into the tumor tissue. The in vivo tumor inhibition results demonstrated that the tumor inhibition rate of the C-H/D/M treated group was 54.05% ± 1.25%. The biosafety results indicated that C-H/D/M did not induce significant damages to the main organs in vivo. Conclusion: C-H/D/M can be used as an ideal non-viral tumor-targeting vector to overcome MDR and enhance the antitumor effect.

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Co-delivery of a RanGTP inhibitory peptide and doxorubicin using dual-loaded liposomal carriers to combat chemotherapeutic resistance in breast cancer cells

Cited by 45 publications

References 58 publications

RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases

RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases

Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery

Cetuximab-Modified Human Serum Albumin Nanoparticles Co-Loaded with Doxorubicin and MDR1 siRNA for the Treatment of Drug-Resistant Breast Tumors

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