publication . Article . 2018

Tumor microenvironment-targeted poly-L-glutamic acid-based combination conjugate for enhanced triple negative breast cancer treatment

Ana Conesa; Sonia Tarazona; Leandro Balzano-Nogueira; Jerónimo Forteza; Ana Armiñán; Francisco Huertas-López; Juan J. Arroyo-Crespo; Cristina Martí; María J. Vicent; David Charbonnier;
Open Access English
  • Published: 01 Dec 2018
  • Country: Spain
Abstract
[EN] The intrinsic characteristics of the tumor microenvironment (TME), including acidic pH and overexpression of hydrolytic enzymes, offer an exciting opportunity for the rational design of TME-drug delivery systems (DDS). We developed and characterized a pH-responsive biodegradable poly-L-glutamic acid (PGA)-based combination conjugate family with the aim of optimizing anticancer effects. We obtained combination conjugates bearing Doxorubicin (Dox) and aminoglutethimide (AGM) with two Dox loadings and two different hydrazone pH sensitive linkers that promote the specific release of Dox from the polymeric backbone within the TME. Low Dox loading coupled with a ...
Subjects
free text keywords: Polymer therapeutics, Polypeptides, Polymer-based combination conjugates, tumor microenvironment, metastatic triple-negative breast cancer, Transcriptomics, ESTADISTICA E INVESTIGACION OPERATIVA, Biophysics, Mechanics of Materials, Bioengineering, Biomaterials, Ceramics and Composites, Rational design, Chemistry, Conjugate, Triple-negative breast cancer, Doxorubicin, medicine.drug, medicine, Aminoglutethimide, Cancer research, Primary tumor, medicine.disease, Linker
Funded by
EC| MyNano
Project
MyNano
Towards the design of Personalised Polymer-based Combination Nanomedicines for Advanced Stage Breast Cancer Patients
  • Funder: European Commission (EC)
  • Project Code: 648831
  • Funding stream: H2020 | ERC | ERC-COG
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