Dual-targeting hybrid peptide-conjugated doxorubicin for drug resistance reversal in breast cancer

Yuan, Shengtao; You, Yiwen; Chen, Yun

doi:10.1016/j.ijpharm.2016.08.016

Cited by 32 publications

(29 citation statements)

References 51 publications

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“…However, little is known concerning the effects of TRIB2 gene knockdown on drug-resistant proteins. Previous studies have found that the downregulation of drug-resistance proteins may partly depend on inhibition of the ERK pathway in cancer (11)(12)(13). In the present study, we explored changes in the ERK signaling pathway after knockdown of the TRIB2 gene in K562/ADM cells.…”

Section: Introductionmentioning

confidence: 92%

TRIB2 knockdown as a regulator of chemotherapy resistance and proliferation via the ERK/STAT3 signaling pathway in human chronic myelogenous leukemia K562/ADM cells

Zhou

et al. 2018

Oncol Rep

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Acquired resistance to chemotherapy plays a critical role in human drug treatment failure in many tumor types. Multidrug resistance (MDR) to Adriamycin (ADM) also limits the efficacy of therapy in human chronic myelogenous leukemia (CML). The overexpression of drug efflux transporters is one mechanism uderlying MDR. In particular, the consistent activation of MDR1 and MDR‑associated protein 1 (MRP1) is involved in drug resistance. In the present study, ADM‑resistant human CML K562/ADM cells were stably transfected with a Tribbles homolog 2 (TRIB2)‑targeted vector. A CCK‑8 assay showed that the half maximal inhibitory concentration (IC50) of ADM and the cell proliferation were lower in the transfected cells compared with that in the parental K562/ADM cells. The mRNA and protein expression levels of MDR1 and MRP1 were determined by reverse transcription‑polymerase chain reaction (RT‑PCR), RT‑quantitative PCR and western blot analysis. The results showed that the expression of MDR1 and MRP1 was significantly reduced in K562/ADM cells transfected with pGPU6/GFP/Neo‑TRIB2. Due to the downregulation of MDR1 and MRP1, the intracellular accumulation of ADM was increased in the transfected cells compared with that in the parental K562/ADM cells. Therefore, the sensitivity of the K562/ADM cells to ADM was enhanced and proliferation was inhibited. Our research revealed that protein expression of the ERK signaling pathway was inhibited by downregulating TRIB2, indicating that the ERK pathway was involved in cell drug resistance and proliferation. Furthermore, we used the ERK‑specific blocker U0126 to demonstrate this phenomenon. In summary, our research suggested that knockdown of TRIB2 could slow cell growth and reverse resistance, implying that TRIB2 is a potential therapy target for resistant human CML.

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Section: Introductionmentioning

confidence: 92%

TRIB2 knockdown as a regulator of chemotherapy resistance and proliferation via the ERK/STAT3 signaling pathway in human chronic myelogenous leukemia K562/ADM cells

Zhou

et al. 2018

Oncol Rep

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“…The NPs showed a longer half life and were cleared much more slowly from the body than the pure drug. DOX from the CPP-CS- co -PNVCL 1 @DOX NPs can be detected in the blood for more than 20 h, and this prolonged circulation should lead to improved antitumor efficacy [48, 49].…”

Section: Resultsmentioning

confidence: 99%

A chitosan-based cascade-responsive drug delivery system for triple-negative breast cancer therapy

Niu

Williams

et al. 2019

J Nanobiotechnol

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Background It is extremely difficult to develop targeted treatments for triple-negative breast (TNB) cancer, because these cells do not express any of the key biomarkers usually exploited for this goal. Results In this work, we develop a solution in the form of a cascade responsive nanoplatform based on thermo-sensitive poly(N-vinylcaprolactam) (PNVCL)-chitosan (CS) nanoparticles (NPs). These are further modified with the cell penetrating peptide (CPP) and loaded with the chemotherapeutic drug doxorubicin (DOX). The base copolymer was optimized to undergo a phase change at the elevated temperatures of the tumor microenvironment. The acid-responsive properties of CS provide a second trigger for drug release, and the inclusion of CPP should ensure the formulations accumulate in cancerous tissue. The resultant CPP-CS-co-PNVCL NPs could self-assemble in aqueous media into spherical NPs of size < 200 nm and with low polydispersity. They are able to accommodate a high DOX loading (14.8% w/w). The NPs are found to be selectively taken up by cancerous cells both in vitro and in vivo, and result in less off-target cytotoxicity than treatment with DOX alone. In vivo experiments employing a TNB xenograft mouse model demonstrated a significant reduction in tumor volume and prolonging of life span, with no obvious systemic toxicity. Conclusions The system developed in this work has the potential to provide new therapies for hard-to-treat cancers.

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“…The results of the study indicated that T10-ERK-Dox efficiently inhibited drug resistance and improve the cytotoxicity of Dox by blocking Pgp-mediated drug efflux and inducing apoptosis. 120 Furthermore, Lelle et al formulated a conjugate consisting of octaarginine CPP (Ac-CRRRRRRRR-NH2) and Dox dimer with high DNA affinity. The cytotoxicity of the peptide-drug conjugate was evaluated against drug-sensitive and Dox-resistant cancer cells, and showed that the conjugate overcame drug resistance in neuroblastoma cells efficiently.…”

Section: Peptides For Targeting Mdr Cancermentioning

confidence: 99%

Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

Kebebe¹,

Liu²,

Wu³

et al. 2018

IJN

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Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents.

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Dual-targeting hybrid peptide-conjugated doxorubicin for drug resistance reversal in breast cancer

Cited by 32 publications

References 51 publications

TRIB2 knockdown as a regulator of chemotherapy resistance and proliferation via the ERK/STAT3 signaling pathway in human chronic myelogenous leukemia K562/ADM cells

TRIB2 knockdown as a regulator of chemotherapy resistance and proliferation via the ERK/STAT3 signaling pathway in human chronic myelogenous leukemia K562/ADM cells

A chitosan-based cascade-responsive drug delivery system for triple-negative breast cancer therapy

Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

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