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Targeting the tumour microenvironment with an enzyme-responsive drug delivery system for the efficient therapy of breast and pancreatic cancers
- Source :
- Chemical Science, Chemical Science, The Royal Society of Chemistry, 2017, 8 (5), pp.3427-3433. ⟨10.1039/C7SC00472A⟩
- Publication Year :
- 2017
- Publisher :
- HAL CCSD, 2017.
-
Abstract
- The development of novel therapeutic strategies allowing the destruction of tumour cells while sparing healthy tissues is one of the main challenges of cancer chemotherapy. Here, we report on the design and antitumour activity of a low-molecular-weight drug delivery system programmed for the selective release of the potent monomethylauristatin E in the tumour microenvironment of solid tumours. After intravenous administration, this compound binds covalently to plasmatic albumin through Michael addition, thereby enabling its passive accumulation in tumours where extracellular β-glucuronidase initiates the selective release of the drug. This targeting device produces outstanding therapeutic efficacy on orthotopic triple-negative mammary and pancreatic tumours in mice (50% and 33% of mice with the respective tumours cured), leading to impressive reduction or even disappearance of tumours without inducing side effects.
- Subjects :
- Drug
Cancer chemotherapy
media_common.quotation_subject
02 engineering and technology
010402 general chemistry
01 natural sciences
Monomethylauristatin E
Extracellular
Medicine
ComputingMilieux_MISCELLANEOUS
media_common
chemistry.chemical_classification
business.industry
Albumin
General Chemistry
[CHIM.CATA]Chemical Sciences/Catalysis
021001 nanoscience & nanotechnology
0104 chemical sciences
3. Good health
Enzyme
chemistry
Immunology
Drug delivery
Cancer research
0210 nano-technology
business
Subjects
Details
- Language :
- English
- ISSN :
- 20416520 and 20416539
- Database :
- OpenAIRE
- Journal :
- Chemical Science, Chemical Science, The Royal Society of Chemistry, 2017, 8 (5), pp.3427-3433. ⟨10.1039/C7SC00472A⟩
- Accession number :
- edsair.doi.dedup.....3bd61bda09672b28f56e60d15bcd742d