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Biomimetic nanoparticles delivered hedgehog pathway inhibitor to modify tumour microenvironment and improved chemotherapy for pancreatic carcinoma
- Source :
- Artificial cells, nanomedicine, and biotechnology. 46(sup1)
- Publication Year :
- 2018
-
Abstract
- The unique tumour microenvironment (TM) of pancreatic ductal adenocarcinoma (PDA) including highly desmoplastic ECM and low tumour perfusion supports a considerable barrier for effective delivery of nanomedicines. Effectively modulating PDA microenvironment to enhance tumour drug delivery represents a pinpoint in the field of PDA treatment. In this study, it was the first time that biomimetic nanoparticles, which were designed in the form of erythrocyte membrane-camouflaged PLGA nanoparticles (MNP), were utilized for PDA microenvironment modulation. Cyclopamine (CYC), an inhibitor of Hedgehog pathway that contributed a lot to desmoplastic ECM of PDA, was selected as the model drug and successfully encapsulated into MNP. Advantages of CYC-loaded MNP (CMNP) included favourable biocompatibility, long circulation time, and powerful TM modulation effect. CMNP could effectively deliver CYC to the tumour site, disrupt tumour ECM, increase functional vessels, and improve tumour perfusion significantly. The combination treatment with CMNP and PTX-loaded MNP (PMNP) successfully improved PTX delivery to tumour, resulting in remarkable tumour growth inhibition in vivo. Therefore, biomimetic nanoparticles provide a new strategy for modulating PDA TM and will have great potential to improve the therapeutic effects of nanomedicines for PDA patients.
- Subjects :
- 0301 basic medicine
Drug
Male
Cyclopamine
Biocompatibility
media_common.quotation_subject
medicine.medical_treatment
education
Biomedical Engineering
Pharmaceutical Science
Medicine (miscellaneous)
Antineoplastic Agents
02 engineering and technology
03 medical and health sciences
chemistry.chemical_compound
Mice
Polylactic Acid-Polyglycolic Acid Copolymer
In vivo
Biomimetic Materials
Cell Line, Tumor
medicine
Human Umbilical Vein Endothelial Cells
Tumor Microenvironment
Animals
Humans
Hedgehog Proteins
Tissue Distribution
media_common
Chemotherapy
Drug Carriers
Mice, Inbred BALB C
Veratrum Alkaloids
Biological Transport
General Medicine
021001 nanoscience & nanotechnology
Hedgehog signaling pathway
Pancreatic Neoplasms
030104 developmental biology
chemistry
Drug delivery
Cancer research
Nanoparticles
Growth inhibition
0210 nano-technology
Biotechnology
Signal Transduction
Subjects
Details
- ISSN :
- 2169141X
- Volume :
- 46
- Issue :
- sup1
- Database :
- OpenAIRE
- Journal :
- Artificial cells, nanomedicine, and biotechnology
- Accession number :
- edsair.doi.dedup.....00d3f3ef101e5ac170f7fc059389ebdd