A pH-sensitive T7 peptide-decorated liposome system for HER2 inhibitor extracellular delivery: An application for the efficient suppression of HER2+ breast cancer

2021 ◽  
Author(s):  
Shuangshuang Zhang ◽  
Qiaomei Sun ◽  
Xu Peng ◽  
Na Gan ◽  
Ludan Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Duration ◽  
Chemotherapeutic Agents ◽  
Ph Sensitive ◽  
Clinical Treatment ◽  
Severe Toxicity ◽  
Her2 Breast Cancer ◽  
Efficient Suppression ◽  
Liposome System

HER2+ breast cancer is highly aggressive and proliferative even after multiple chemotherapy regimens. At present, the available clinical treatment duration of chemotherapeutic agents is limited by severe toxicity to noncancerous...

Synthesis and In vitro/In vivo Characterization of Raloxifene Grafted Poly(Styrene Maleic Acid)-Poly(Amide-Ether-Ester-Imide) Micelles for Targeted Delivery of Docetaxel in G Protein-Coupled Estrogen Receptor Breast Cancer

2019 ◽  
Vol 18 (14) ◽  
pp. 2017-2031 ◽  
Author(s):  
Jaleh Varshosaz ◽  
Saeedeh Enteshari ◽  
Farshid Hassanzadeh ◽  
Batool Hashemi-Beni ◽  
Mohsen Minaiyan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Maleic Acid ◽  
Targeted Delivery ◽  
Chemotherapeutic Agents ◽  
Whole Body ◽  
Toxicity Tests ◽  
Severe Toxicity ◽  
Ether Ester

Background: To reduce the nonspecifically distribution of chemotherapeutic agents throughout the whole body, which causes severe toxicity in normal tissues, targeting them towards a receptor overexpressed on tumor tissue, is a promising method for cancer therapy. Objective: The aim of the present study was development of novel copolymeric micelles of raloxifene targeted Styrene Maleic Acid-Poly Amide Ether Ester Imide-Poly Ethylene Glycol (SMA-PAEEI-PEG-RA) and loading them with Docetaxel (DTX). Methods: Successful synthesis of the targeted copolymer was confirmed by FTIR and C-NMR spectroscopy. The micelles physicochemical properties like morphology, particle size, poly dispersity index, zeta potential, drug loading, release, stability, in vitro cytotoxicity and cellular uptake were analyzed. The in vivo antitumor activity of DTX-loaded micelles were assessed and compared with free DTX and non-targeted micelles in breast cancer bearing Balb-c mice. Results: Particle sizes, zeta potentials and the encapsulation efficiency of the drug in targeted micelles were 115.9- 142.8 nm, -4.9 to -12.9 mV, and 54.1-67.8%, respectively. Cell toxicity tests showed that IC50 of DTX-loaded SMAPAEEI- PEG-RA micelles increased five-fold as compared with free DTX. Survival rate of the mice improved more effectively than free DTX so that, the percentage of increase in lifespan (ILS%) and the tumor inhibition ratio (TIR) changed from 41.66% and 51.19% in free drug to 83.33% and 78.57% in the targeted micelles, respectively. Conclusion: Therefore, the raloxifene conjugated PEG-derived micelles may provide a novel and effective delivery system for DTX in breast cancer.

Systemic Delivery of Aptamer-Conjugated XBP1 siRNA Nanoparticles for Efficient Suppression of HER2+ Breast Cancer

2020 ◽  
Vol 12 (29) ◽  
pp. 32360-32371 ◽  
Author(s):  
Long Zhang ◽  
Chaofeng Mu ◽  
Tinghong Zhang ◽  
Yingying Wang ◽  
Yili Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Delivery ◽  
Her2 Breast Cancer ◽  
Efficient Suppression

scholarly journals POLRMT as a Novel Susceptibility Gene for Cardiotoxicity in Epirubicin Treatment of Breast Cancer Patients

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1942
Author(s):  
Alejandro Velasco-Ruiz ◽  
Rocio Nuñez-Torres ◽  
Guillermo Pita ◽  
Hans Wildiers ◽  
Diether Lambrechts ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genome Wide Association Study ◽  
Mitochondrial Gene ◽  
Susceptibility Gene ◽  
Heart Tissue ◽  
Chemotherapeutic Agents ◽  
Individual Variability ◽  
Severe Toxicity ◽  
Breast Cancer Patients ◽  
Single Nucleotide Variants

Anthracyclines are among the most used chemotherapeutic agents in breast cancer (BC). However their use is hampered by anthracycline-induced cardiotoxicity (AIC). The currently known clinical and genetic risk factors do not fully explain the observed inter-individual variability and only have a limited ability to predict which patients are more likely to develop this severe toxicity. To identify novel predictive genes, we conducted a two-stage genome-wide association study in epirubicin-treated BC patients. In the discovery phase, we genotyped over 700,000 single nucleotide variants in a cohort of 227 patients. The most interesting finding was rs62134260, located 4kb upstream of POLRMT (OR = 5.76, P = 2.23 × 10−5). We replicated this association in a validation cohort of 123 patients (P = 0.021). This variant regulates the expression of POLRMT, a gene that encodes a mitochondrial DNA-directed RNA polymerase, responsible for mitochondrial gene expression. Individuals harbouring the risk allele had a decreased expression of POLRMT in heart tissue that may cause an impaired capacity to maintain a healthy mitochondrial population in cardiomyocytes under stressful conditions, as is treatment with epirubicin. This finding suggests a novel molecular mechanism involved in the development of AIC and may improve our ability to predict patients who are at risk.

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