scholarly journals The Therapeutic Efficacy of Dendrimer and Micelle Formulations for Breast Cancer Treatment

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1212
Author(s):  
Sibusiso Alven ◽  
Blessing Atim Aderibigbe
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Resistance ◽  
Side Effects ◽  
Anticancer Drugs ◽  
Drug Toxicity ◽  
Multi Drug Resistance ◽  
Drug Bioavailability

Breast cancer is among the most common types of cancer in women and it is the cause of a high rate of mortality globally. The use of anticancer drugs is the standard treatment approach used for this type of cancer. However, most of these drugs are limited by multi-drug resistance, drug toxicity, poor drug bioavailability, low water solubility, poor pharmacokinetics, etc. To overcome multi-drug resistance, combinations of two or more anticancer drugs are used. However, the combination of two or more anticancer drugs produce toxic side effects. Micelles and dendrimers are promising drug delivery systems that can overcome the limitations associated with the currently used anticancer drugs. They have the capability to overcome drug resistance, reduce drug toxicity, improve the drug solubility and bioavailability. Different classes of anticancer drugs have been loaded into micelles and dendrimers, resulting in targeted drug delivery, sustained drug release mechanism, increased cellular uptake, reduced toxic side effects of the loaded drugs with enhanced anticancer activity in vitro and in vivo. This review article reports the biological outcomes of dendrimers and micelles loaded with different known anticancer agents on breast cancer in vitro and in vivo.

PEAK1 promotes invasion and metastasis and confers drug resistance in breast cancer

2021 ◽  
Author(s):  
xingang wang ◽  
YAN ZHENG ◽  
YU WANG
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Multi Drug Resistance ◽  
Cancer Tissues

Abstract Background and AimsPseudopodium-enriched atypical kinase 1 (PEAK1) has reported to be upregulated in human malignancies and related with poor prognosis. Enhanced PEAK1 expression facilitates tumor cell survival, invasion, metastasis and chemoresistance. However, the role of PEAK1 in breast cancer is not clear. Here, we investigated the PEAK1 expression in breast cancer and analyzed its relation with clinicopathological status and chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated the role of PEAK1 on breast cancer cells in vitro and in vivo. MethodsImmunohistochemistry (IHC) was performed in 112 surgical resected breast cancer tissues. The associations between clinicopathological status, multi-drug resistance and PEAK1 expression were determined. Effect of PEAK1 overexpression or down-expression on proliferation, colony formation, invasion, migration, metastasis and Doxorubicin sensitivity in the MCF-7 cells in vitro and in vivo was detected. ResultsPEAK1 was overexpressed in breast cancer tissues and NAC -resistant breast cancer tissues. High PEAK1 expression was related with tumor size, high tumor grade, T stage, LN metastasis, recurrence, Ki-67 expression, Her-2 expression and multi-drug resistance. Targeting PEAK1 inhibited cell growth, invasion, metastasis and reversed chemoresistance to Doxorubicin in breast cancer cells in vitro and in vivo. ConclusionHigh PEAK1 expression was associated with invasion, metastasis and chemoresistance of breast cancers. Furthermore, targeting PEAK1 could inhibit cell growth and metastasis, and reverse chemoresistance in breast cancer cells, which provides an effective treatment strategies for breast cancer.

scholarly journals Controllable Drug Delivery by Na+/K+ ATPase α1 Targeting Peptide Conjugated DSPE-PEG Nanocarriers for Breast Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110278
Author(s):  
Yayan Yang ◽  
Qian Feng ◽  
Chuanfeng Ding ◽  
Wei Kang ◽  
Xiufeng Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Click Reaction ◽  
Chemotherapy Drugs ◽  
Targeting Peptide ◽  
And Migration

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

scholarly journals Advances in Hybrid Polymer-Based Materials for Sustained Drug Release

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Lígia N. M. Ribeiro ◽  
Ana C. S. Alcântara ◽  
Gustavo H. Rodrigues da Silva ◽  
Michelle Franz-Montan ◽  
Silvia V. G. Nista ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Toxicity ◽  
Drug Delivery Systems ◽  
Hybrid Polymer ◽  
Future Perspectives ◽  
Sustained Drug Release ◽  
Physicochemical Stability ◽  
Traditional Drug

The use of biomaterials composed of organic pristine components has been successfully described in several purposes, such as tissue engineering and drug delivery. Drug delivery systems (DDS) have shown several advantages over traditional drug therapy, such as greater therapeutic efficacy, prolonged delivery profile, and reduced drug toxicity, as evidenced by in vitro and in vivo studies as well as clinical trials. Despite that, there is no perfect delivery carrier, and issues such as undesirable viscosity and physicochemical stability or inability to efficiently encapsulate hydrophilic/hydrophobic molecules still persist, limiting DDS applications. To overcome that, biohybrid systems, originating from the synergistic assembly of polymers and other organic materials such as proteins and lipids, have recently been described, yielding molecularly planned biohybrid systems that are able to optimize structures to easily interact with the targets. This work revised the biohybrid DDS clarifying their advantages, limitations, and future perspectives in an attempt to contribute to further research of innovative and safe biohybrid polymer-based system as biomaterials for the sustained release of active molecules.

scholarly journals CBP/β-Catenin/FOXM1 Is a Novel Therapeutic Target in Triple Negative Breast Cancer

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 525 ◽  
Author(s):  
Alexander Ring ◽  
Cu Nguyen ◽  
Goar Smbatyan ◽  
Debu Tripathy ◽  
Min Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Drug Resistance ◽  
Triple Negative Breast Cancer ◽  
Therapeutic Target ◽  
Triple Negative ◽  
Creb Binding Protein ◽  
Novel Therapeutic

Background: Triple negative breast cancers (TNBCs) are an aggressive BC subtype, characterized by high rates of drug resistance and a high proportion of cancer stem cells (CSC). CSCs are thought to be responsible for tumor initiation and drug resistance. cAMP-response element-binding (CREB) binding protein (CREBBP or CBP) has been implicated in CSC biology and may provide a novel therapeutic target in TNBC. Methods: RNA Seq pre- and post treatment with the CBP-binding small molecule ICG-001 was used to characterize CBP-driven gene expression in TNBC cells. In vitro and in vivo TNBC models were used to determine the therapeutic effect of CBP inhibition via ICG-001. Tissue microarrays (TMAs) were used to investigate the potential of CBP and associated proteins as biomarkers in TNBC. Results: The CBP/ß-catenin/FOXM1 transcriptional complex drives gene expression in TNBC and is associated with increased CSC numbers, drug resistance and poor survival outcome. Targeting of CBP/β-catenin/FOXM1 with ICG-001 eliminated CSCs and sensitized TNBC tumors to chemotherapy. Immunohistochemistry of TMAs demonstrated a significant correlation between FOXM1 expression and TNBC subtype. Conclusion: CBP/β-catenin/FOXM1 transcriptional activity plays an important role in TNBC drug resistance and CSC phenotype. CBP/β-catenin/FOXM1 provides a molecular target for precision therapy in triple negative breast cancer and could form a rationale for potential clinical trials.

scholarly journals Efficacy of Polymer-Based Nanocarriers for Co-Delivery of Curcumin and Selected Anticancer Drugs

Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1556 ◽  
Author(s):  
Sibusiso Alven ◽  
Blessing Atim Aderibigbe
Keyword(s):  
Drug Resistance ◽  
Combination Therapy ◽  
Anticancer Drugs ◽  
Water Solubility ◽  
Review Article ◽  
High Rate ◽  
Therapeutic Outcomes ◽  
Biological Outcomes

Cancer remains a heavy health burden resulting in a high rate of mortality around the world. The presently used anticancer drugs suffer from several shortcomings, such as drug toxicity, poor biodegradability and bioavailability, and poor water solubility and drug resistance. Cancer is treated effectively by combination therapy whereby two or more anticancer drugs are employed. Most of the combination chemotherapies result in a synergistic effect and overcome drug resistance. Furthermore, the design of polymer-based nanocarriers for combination therapy has been reported by several researchers to result in promising therapeutic outcomes in cancer treatment. Curcumin exhibits good anticancer activity but its poor bioavailability has resulted in its incorporation into several polymer-based nanocarriers resulting in good biological outcomes. Furthermore, the incorporation of curcumin together with other anticancer drugs have been reported to result in excellent therapeutic outcomes in vivo and in vitro. Due to the potential of polymer-based nanocarriers, this review article will be focused on the design of polymer-based nanocarriers loaded with curcumin together with other anticancer drugs.

scholarly journals Reversal of multi-drug resistance by pSUPER-shRNA-mdr1 in vivo and in vitro

2009 ◽  
Vol 15 (4) ◽  
pp. 431 ◽  
Author(s):  
Guang-Dong Pan ◽  
Jian-Qing Yang ◽  
Lv-Nan Yan ◽  
Guang-Ping Chu ◽  
Qiang Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multi Drug Resistance

scholarly journals Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1412
Author(s):  
Maria Grazia Ferraro ◽  
Marialuisa Piccolo ◽  
Gabriella Misso ◽  
Francesco Maione ◽  
Daniela Montesarchio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Preclinical Development ◽  
Cell Death Pathways ◽  
Complex Information ◽  
Ru Complexes ◽  
Therapeutic Alternatives

In this review we have showcased the preclinical development of original amphiphilic nanomaterials designed for ruthenium-based anticancer treatments, to be placed within the current metallodrugs approach leading over the past decade to advanced multitarget agents endowed with limited toxicity and resistance. This strategy could allow for new options for breast cancer (BC) interventions, including the triple-negative subtype (TNBC) with poor therapeutic alternatives. BC is currently the second most widespread cancer and the primary cause of cancer death in women. Hence, the availability of novel chemotherapeutic weapons is a basic requirement to fight BC subtypes. Anticancer drugs based on ruthenium are among the most explored and advanced next-generation metallotherapeutics, with NAMI-A and KP1019 as two iconic ruthenium complexes having undergone clinical trials. In addition, many nanomaterial Ru complexes have been recently conceived and developed into anticancer drugs demonstrating attractive properties. In this field, we focused on the evaluation of a Ru(III) complex—named AziRu—incorporated into a suite of both zwitterionic and cationic nucleolipid nanosystems, which proved to be very effective for the in vivo targeting of breast cancer cells (BBC). Mechanisms of action have been widely explored in the context of preclinical evaluations in vitro, highlighting a multitarget action on cell death pathways which are typically deregulated in neoplasms onset and progression. Moreover, being AziRu inspired by the well-known NAMI-A complex, information on non-nanostructured Ru-based anticancer agents have been included in a precise manner.

scholarly journals LncRNA FEZF1-AS1 Promotes Multi-Drug Resistance of Gastric Cancer Cells via Upregulating ATG5

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhifu Gui ◽  
Zhenguo Zhao ◽  
Qi Sun ◽  
Guoyi Shao ◽  
Jianming Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Underlying Mechanism ◽  
Multi Drug Resistance ◽  
Gastric Cancer Cells ◽  
Poor Overall Survival

Long non-coding RNAs (lncRNAs) play important roles in human cancers including gastric cancer (GC). Dysregulation of lncRNAs is involved in a variety of pathological activities associated with gastric cancer progression and chemo-resistance. However, the role and molecular mechanisms of FEZF1-AS1 in chemoresistance of GC remain unknown. In this study, we aimed to determine the role of FEZF1-AS1 in chemoresistance of GC. The level of FEZF1-AS1 in GC tissues and GC cell lines was assessed by qRT-PCR. Our results showed that the expression of FEZF1-AS1 was higher in gastric cancer tissues than in adjacent normal tissues. Multivariate analysis identified that high level of FEZF1-AS1 is an independent predictor for poor overall survival. Increased FEZF1-AS1 expression promoted gastric cancer cell proliferation in vitro. Additionally, FEZF1-AS1 was upregulated in chemo-resistant GC tissues. The regulatory effect of FEZF1-AS1 on multi-drug resistance (MDR) in GC cells and the underlying mechanism was investigated. It was found that increased FEZF1-AS1 expression promoted chemo-resistance of GC cells. Molecular interactions were determined by RNA immunoprecipitation (RIP) and the results showed that FEZF1-AS1 regulated chemo-resistance of GC cells through modulating autophagy by directly targeting ATG5. The proliferation and autophagy of GC cells promoted by overexpression of LncFEZF1-AS1 was suppressed when ATG5 was knocked down. Moreover, knockdown of FEZF1-AS1 inhibited tumor growth and increased 5-FU sensitivity in GC cells in vivo. Taken together, this study revealed that the FEZF1-AS1/ATG5 axis regulates MDR of GC cells via modulating autophagy.

scholarly journals Plasmodium falciparum Multidrug Resistance Proteins (pfMRPs)

2021 ◽  
Vol 12 ◽  
Author(s):  
José Pedro Gil ◽  
Cláudia Fançony
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Multi Drug Resistance ◽  
Multidrug Resistance Proteins ◽  
Resistance Proteins ◽  
Diverse Groups ◽  
Endogenous Substances

The capacity of the lethal Plasmodium falciparum parasite to develop resistance against anti-malarial drugs represents a central challenge in the global control and elimination of malaria. Historically, the action of drug transporters is known to play a pivotal role in the capacity of the parasite to evade drug action. MRPs (Multidrug Resistance Protein) are known in many phylogenetically diverse groups to be related to drug resistance by being able to handle a large range of substrates, including important endogenous substances as glutathione and its conjugates. P. falciparum MRPs are associated with in vivo and in vitro altered drug response, and might be important factors for the development of multi-drug resistance phenotypes, a latent possibility in the present, and future, combination therapy environment. Information on P. falciparum MRPs is scattered in the literature, with no specialized review available. We herein address this issue by reviewing the present state of knowledge.

scholarly journals Rutin: A Flavonoid as an Effective Sensitizer for Anticancer Therapy; Insights into Multifaceted Mechanisms and Applicability for Combination Therapy

2021 ◽  
Vol 2021 ◽  
pp. 1-10 ◽  
Author(s):  
Atefeh Satari ◽  
Sorayya Ghasemi ◽  
Solomon Habtemariam ◽  
Shirin Asgharian ◽  
Zahra Lorigooini
Keyword(s):  
Drug Resistance ◽  
Side Effects ◽  
Therapeutic Agent ◽  
Promising Candidate ◽  
Chemotherapy Drugs ◽  
Anticancer Properties ◽  
Chemotherapy Side Effects ◽  
Prostate Cancers

Rutin is a unique antioxidant flavonoid that is mainly found in fruit, vegetables, cereals, and many other plant-based human diets. This review aims to highlight the in vitro anticancer properties of rutin including combination therapeutic strategies. Literature resources were gathered through PubMed, Scopus, Web of Science, and Google Scholar databases that cover the period of 1995–2021. Rutin is demonstrated to inhibit the proliferation of breast, colon, lung, and prostate cancers and other tumors. Furthermore, rutin alone or in combination with other therapeutic agents has been shown to regulate several signalling pathways involving the Ras/Raf and PI3K/Akt, MAPK, and TGF-β2/Smad2/3Akt/PTEN, etc., which are related to the processes of carcinogenesis and induction of apoptosis. The combination of rutin with other chemotherapy drugs may benefit on prevention of tumor cells by decreasing drug resistance and chemotherapy side effects. Moreover, rutin induces apoptosis synergistically with the therapeutic agent. More in vivo and clinical data are however needed to evaluate the true potential of rutin as an anticancer agent as an adjuvant. The present review highlights the effects of rutin which can be a promising candidate in combination with other antitumor drugs or alone for cancer treatment in vitro. Also, rutin can lead to decrease in drug resistance and chemotherapeutic side effects.

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