Cancer associated fibroblasts (CAFs) are the most abundant, genetically stable stroma cells and localize near blood vessels within “finger-like” collagen-rich stroma, which lead to restrained drug transport in dense stroma instead of tumor cells inside tumor mass, especially for targeting micelles. Meanwhile, the bioactive cytokines secreted by stroma cells result in microenvironment mediated drug resistance (TMDR). Hence, a biologically inspired Telmisartan (Tel) grafting glycolipid micelles (Tel-CSOSA) are constructed, which can sequentially target angiotensin II type I receptor (AT1R) overexpressed on both CAFs and tumor cells. More Tel-CSOSA are demonstrated to specifically accumulate in tumor site compared to CSOSA. In addition, the retention of Tel-CSOSA is primarily prolonged around tumor vessel in virtue of CAFs targeting and the stroma barrier. In contrast, the elimination of “finger-like” ECM resulting from CAFs apoptosis by Tel-CSOSA/DOX contributes to a more uniform and deeper penetration post-administration, which can enforce subsequently tumor cells targeting. Meanwhile, cytokines are decreased along with CAFs apoptosis so that tumor cells are more vulnerable to chemotherapeutics. Collectively, this strategy of sequentially targeting CAFs and tumor cells could synergistically increase antitumor therapy with reversed TMDR.
Biomaterials – Elsevier
Published: Apr 1, 2018
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera