Improved tumor targeting and penetration by a dual-functional poly(amidoamine) dendrimer for the therapy of triple-negative breast cancer

2019 ◽  
Vol 7 (23) ◽  
pp. 3724-3736 ◽  
Author(s):  
Changliang Liu ◽  
Houqian Gao ◽  
Zijian Zhao ◽  
Iman Rostami ◽  
Chen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Triple Negative Breast Cancer ◽  
Tumor Targeting ◽  
Triple Negative ◽  
Pamam Dendrimer ◽  
Tat Peptide ◽  
Dual Functional

A dual-functional drug delivery system based on the conjugation of PAMAM dendrimer with EBP-1 and TAT peptide was established for the therapy of triple-negative breast cancer.

scholarly journals The Synthesis of Glutamine-Functionalized Block Polymer and Its Application in Triple-Negative Breast Cancer Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yi-Zhi Zhu ◽  
Di Xu ◽  
Zhen Liu ◽  
Tian Tian ◽  
Fei Deng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Triple Negative Breast Cancer ◽  
Tumor Targeting ◽  
Triple Negative ◽  
Drug Carrier ◽  
Block Polymer

Triple-negative breast cancer (TNBC) is a highly malignant tumor. At present, there are still no targeted drugs for TNBC. Clinical chemotherapeutic drugs, such as doxorubicin (DOX), have the characteristic of nontargeted distribution in treatment of TNBC, causing severe side effects. Therefore, new target treatment strategies for TNBC are of urgent need. It was speculated that glutamine could be a potential target because it is in high demand by TNBC. In this study, we found that the transporter for glutamine, ASCT2 (solute carrier family 1 member 5 (SLC1A5)), is highly expressed in TNBC by analysis of data from The Cancer Genome Atlas (TCGA) and experiments in vitro. Based on this, glutamine was grafted onto a polymeric drug carrier in order to develop a tumor-targeting drug delivery system for treatment of TNBC. Firstly, pH-responsive glutamine-PEG5000-b-PAE10000 (Gln-PEG-b-PAE) copolymers were synthesized using Fmoc-PEG5000-b-PAE10000 (Fmoc-PEG-b-PAE) copolymers. Then, Gln-PEG-b-PAE@DOX micelles were prepared by loading DOX to Gln-PEG-b-PAE copolymer using a solvent casting technology. In vitro, Gln-PEG-b-PAE@DOX micelles exhibited pH-dependent micellization-decellularization behavior; namely, they can rapidly release DOX in acidic environment of pH 6.0 but release very slowly in physiological condition. Moreover, glutamine competition experiment showed that Gln-PEG-b-PAE@DOX micelles had the ability to target MDA-MB-231 cells. Compared to free DOX, Gln-PEG-b-PAE@DOX micelles had significantly greater cytotoxic effect and antiproliferative activity against MDA-MB-231 cells. In vivo, compared to free DOX and mPEG-b-PAE@DOX micelles, Gln-PEG-b-PAE@DOX micelles significantly inhibited tumor growth in tumor-bearing mice. Therefore, Gln-PEG-b-PAE@DOX micelles, as a tumor-targeting drug delivery system, may provide a new method for the treatment of TNBC.

scholarly journals A self-assembled RNA-triple helix hydrogel drug delivery system targeting triple-negative breast cancer

2020 ◽  
Vol 8 (16) ◽  
pp. 3527-3533 ◽  
Author(s):  
Lairong Ding ◽  
Junwei Li ◽  
Changrong Wu ◽  
Feng Yan ◽  
Xuemei Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Triple Negative Breast Cancer ◽  
Triple Helix ◽  
Triple Negative ◽  
Breast Cancers ◽  
Self Assembled ◽  
Rna Triple Helix

A novel RNA-triple-helix hydrogel for treatment of triple negative breast cancers (TNBCs) by incorporating RNA-triple-helix and siRNA duplexes of CXCR4 into the same RNA nanoparticles was developed, without the synthetic polycationic reagents.

Lignin-graft-PLGA drug-delivery system improves efficacy of MEK1/2 inhibitors in triple-negative breast cancer cell line

Nanomedicine ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. 981-1000
Author(s):  
C Ethan Byrne ◽  
Carlos E Astete ◽  
Manibarathi Vaithiyanathan ◽  
Adam T Melvin ◽  
Mahsa Moradipour ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cell Line ◽  
Drug Delivery System ◽  
Delivery System ◽  
Triple Negative Breast Cancer ◽  
Targeted Therapies ◽  
Triple Negative ◽  
Mesenchymal Transition

Aim: Few targeted therapies are available for triple-negative breast cancer (TNBC) patients. Here, we propose a novel alkaline-lignin-conjugated-poly(lactic- co-glycolic acid) (L-PLGA) nanoparticle drug delivery system to improve the efficacy of targeted therapies. Materials & methods: L-PLGA nanoparticles (NPs) loaded with the MEK1/2 inhibitor GDC-0623 were characterized, tested in vitro on MDA-MB-231 TNBC cell line and compared with loaded PLGA NPs. Results: Loaded L-PLGA NPs were less than half the size of PLGA NPs, had slower drug release and improved the efficacy of GDC-0623 when tested in vitro. We demonstrated that GDC-0623 reversed epithelial-to-mesenchymal transition in TNBC. Conclusion: Our findings indicate that L-PLGA NPs are superior to PLGA NPs in delivering GDC-0623 to cancer cells for improved efficacy in vitro.

scholarly journals Folic Acid – targeted Doxorubicin drug delivery system for triple-negative breast cancer treatment.

2020 ◽  
Author(s):  
Sophia Antimisiaris ◽  
Helen Lamprou ◽  
Spyridon Mourtas ◽  
Maria Mantzari ◽  
Antonia Maraziotis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Folic Acid ◽  
Cancer Treatment ◽  
Drug Delivery System ◽  
Delivery System ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Treatment

scholarly journals Abstract A105: Novel lignin-conjugated PLGA drug delivery system improves efficacy of MEK1/2 inhibitor in triple negative breast cancer

2019 ◽  
Author(s):  
Ethan Byrne ◽  
Carlos E. Astete ◽  
Manibarathi Vaithiyanathan ◽  
Adam T Melvin ◽  
Mahsa Moradipour ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Triple Negative Breast Cancer ◽  
Triple Negative

scholarly journals Optimizing cisplatin delivery to triple-negative breast cancer through novel EGFR aptamer-conjugated polymeric nanovectors

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Lisa Agnello ◽  
Silvia Tortorella ◽  
Annachiara d’Argenio ◽  
Clarissa Carbone ◽  
Simona Camorani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Tumor Targeting ◽  
Triple Negative ◽  
Ex Vivo ◽  
Treatment Options ◽  
Negative Control ◽  
Therapeutic Effects ◽  
Metastatic Setting

Abstract Background Management of triple-negative breast cancer (TNBC) is still challenging because of its aggressive clinical behavior and limited targeted treatment options. Cisplatin represents a promising chemotherapeutic compound in neoadjuvant approaches and in the metastatic setting, but its use is limited by scarce bioavailability, severe systemic side effects and drug resistance. Novel site-directed aptamer-based nanotherapeutics have the potential to overcome obstacles of chemotherapy. In this study we investigated the tumor targeting and the anti-tumorigenic effectiveness of novel cisplatin-loaded and aptamer-decorated nanosystems in TNBC. Methods Nanotechnological procedures were applied to entrap cisplatin at high efficacy into polymeric nanoparticles (PNPs) that were conjugated on their surface with the epidermal growth factor receptor (EGFR) selective and cell-internalizing CL4 aptamer to improve targeted therapy. Internalization into TNBC MDA-MB-231 and BT-549 cells of aptamer-decorated PNPs, loaded with BODIPY505-515, was monitored by confocal microscopy using EGFR-depleted cells as negative control. Tumor targeting and biodistribution was evaluated by fluorescence reflectance imaging upon intravenously injection of Cyanine7-labeled nanovectors in nude mice bearing subcutaneous MDA-MB-231 tumors. Cytotoxicity of cisplatin-loaded PNPs toward TNBC cells was evaluated by MTT assay and the antitumor effect was assessed by tumor growth experiments in vivo and ex vivo analyses. Results We demonstrate specific, high and rapid uptake into EGFR-positive TNBC cells of CL4-conjugated fluorescent PNPs which, when loaded with cisplatin, resulted considerably more cytotoxic than the free drug and nanovectors either unconjugated or conjugated with a scrambled aptamer. Importantly, animal studies showed that the CL4-equipped PNPs achieve significantly higher tumor targeting efficiency and enhanced therapeutic effects, without any signs of systemic toxicity, compared with free cisplatin and untargeted PNPs. Conclusions Our study proposes novel and safe drug-loaded targeted nanosystems for EGFR-positive TNBC with excellent potential for the application in cancer diagnosis and therapy.

Macromolecular HPMA-Based Nanoparticles with Cholesterol for Solid-Tumor Targeting: Detailed Study of the Inner Structure of a Highly Efficient Drug Delivery System

2012 ◽  
Vol 13 (8) ◽  
pp. 2594-2604 ◽  
Author(s):  
Sergey K. Filippov ◽  
Petr Chytil ◽  
Petr V. Konarev ◽  
Margarita Dyakonova ◽  
ChristineM. Papadakis ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Solid Tumor ◽  
Tumor Targeting ◽  
Highly Efficient
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