scholarly journals DR-5 and DLL-4 mAb Functionalized SLNs of Gamma-Secretase Inhibitors- An Approach for TNBC Treatment

2020 ◽  
Author(s):  
Mamta Kumari ◽  
Praveen T. Krishnamurthy ◽  
Sai kiran S. S. Pinduprolu ◽  
Piyong Sola
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Side Effects ◽  
Notch Signaling ◽  
Death Receptor ◽  
Death Receptor 5 ◽  
Gamma Secretase ◽  
Extrinsic Pathway ◽  
Cancer Subtypes ◽  
Target Side

Triple-negative breast cancer (TNBC) is the most aggressive and heterogeneous cancer subtypes. High rates of metastasis, poor prognosis, and drug resistance are the major problems associated with TNBC. The current chemotherapeutics eliminate only the bulk tumor cells (non-BCSCs) and do not affect breast cancer stem cells (BCSCs). The BCSCs which are left behind after chemotherapy is reported to promote recurrence and metastasis of TNBC. Death receptor-5 (DR-5) is exclusively expressed in TNBCs and mediates the extrinsic pathway of apoptosis. DR-5, therefore, can be exploited for targeted drug delivery and to induce apoptosis. Gamma-secretase mediated Notch signaling in BCSCs regulates its proliferation, differentiation, and metastasis. The endogenous ligand, Delta-like ligand 4 (DLL4), is reported to activate this Notch signaling in TNBC. Blocking this signaling pathway using both gamma-secretase inhibitors (GSIs) and DLL4 monoclonal antibody (mAb) may produce synergistic benefits. Further, the GSIs (DAPT, LY-411575, RO4929097, MK0752, etc.) suffer from poor bioavailability and off-target side effects such as diarrhea, suppression of lymphopoiesis, headache, hypertension, fatigue, and ventricular dysfunctions. In this hypothesis, we discuss Solid lipid nanoparticles (SLNs) based drug delivery systems containing GSIs and surface modified with DR-5 and DLL4 monoclonal antibodies (mAb) to effectivity target and treat TNBC. The delivery system is designed to deliver the drug cargo precisely to TNBCs through its DR-5 receptors and hence expected to reduce the off-target side effects of GSIs. Further, DLL4 mAb and GSIs are expected to act synergistically to block the Notch signal mediated BCSCs proliferation, differentiation, and metastasis.

Targeted Drug Therapy to Overcome Chemoresistance in Triple-negative Breast Cancer

2020 ◽  
Vol 20 (8) ◽  
pp. 559-572
Author(s):  
Mamta Kumari ◽  
Praveen Thaggikuppe Krishnamurthy ◽  
Piyong Sola
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Side Effects ◽  
Triple Negative Breast Cancer ◽  
Anticancer Agents ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Cancer Subtype ◽  
Prevent Tumor Growth ◽  
Target Side

Triple-negative Breast Cancer (TNBC) is the most aggressive and prevailing breast cancer subtype. The chemotherapeutics used in the treatment of TNBC suffer from chemoresistance, dose-limiting toxicities and off-target side effects. As a result, conventional chemotherapeutics are unable to prevent tumor growth, metastasis and result in failure of therapy. Various new targets such as BCSCs surface markers (CD44, CD133, ALDH1), signaling pathways (IL-6/JAK/STAT3, notch), pro and anti-apoptotic proteins (Bcl-2, Bcl-xL, DR4, DR5), hypoxic factors (HIF-1α, HIF-2α) and drug efflux transporters (ABCC1, ABCG2 and ABCB1) have been exploited to treat TNBC. Further, to improve the efficacy and safety of conventional chemotherapeutics, researchers have tried to deliver anticancer agents specifically to the TNBCs using nanocarrier based drug delivery. In this review, an effort has been made to highlight the various factors responsible for the chemoresistance in TNBC, novel molecular targets of TNBC and nano-delivery systems employed to achieve sitespecific drug delivery to improve efficacy and reduce off-target side effects.

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.

Application of Carbon Nanotubes in Breast Cancer Therapy

Drug Research ◽  
2019 ◽  
Author(s):  
Mahdis Tajabadi
Keyword(s):  
Breast Cancer ◽  
Carbon Nanotubes ◽  
Drug Delivery ◽  
Side Effects ◽  
Tumor Therapy ◽  
Single Walled Carbon Nanotubes ◽  
Low Doses ◽  
High Efficacy ◽  
Breast Cancer Therapy ◽  
Walled Carbon Nanotubes

AbstractConjugated single-walled carbon nanotubes (SWNT) have been shown to be promising in cancer-targeted accumulation and is biocompatible, easily excreted, and possesses little toxicity. The present study aims at reviewing the recent advancements in carbon nanotubes especially SWNT for improving the treatment of breast cancer. Nanotube drug delivery system is a potential high efficacy therapy with minimum side effects for future tumor therapy with low doses of drug.

A new oridonin analog suppresses triple-negative breast cancer cells and tumor growth via the induction of death receptor 5

2016 ◽  
Vol 380 (2) ◽  
pp. 393-402 ◽  
Author(s):  
Jing Wu ◽  
Ye Ding ◽  
Chuan-Huizhi Chen ◽  
Zhongmei Zhou ◽  
Chunyong Ding ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Death Receptor ◽  
Death Receptor 5
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