Affiliation:
1. School of Life Science and Engineering Southwest Jiaotong University Chengdu 610031 P. R. China
2. Key Laboratory of Advanced Technologies of Materials Ministry of Education School of Materials Science and Engineering Southwest Jiaotong University Chengdu 610031 P. R. China
Abstract
AbstractIn the treatment of solid tumors, the complex barriers composed of cancer‐associated fibroblasts (CAFs) prevent drug delivery and T cells infiltration into tumor tissues. Although nanocarriers hold great prospects in drug delivery, fibrosis causes the biological barrier and immunosuppressive tumor microenvironment (ITM) that impairs the anti‐tumor efficacy of nanocarriers. Here, a small dendritic macromolecule loaded with doxorubicin (PAMAM‐ss‐DOX) (DP) is synthesized and encapsulated into pH‐responsive nanoliposome, together with adjuvant toll‐like receptor 7/8 (TLR7/8) agonist resiquimod (R848) and losartan (LOS). The pH‐responsive liposome facilitates the simultaneous and effective delivery of DP, R848, and LOS, which can decompose and release these drugs under the acidic tumor microenvironment. The small sized DP (≈25 nm) with the ability to penetrate into tumor tissue and immunogenic cell death (ICD) can reverse the ITM and elicit immune response, which is equivalent to the effect of an in situ vaccine. Moreover, LOS reduces the activity of CAFs effectively, which can contribute to the infiltration of T cells. Therefore, this nano‐platform provides a new therapeutic strategy for enhanced chemo‐immunotherapy.
Funder
National Natural Science Foundation of China
Fundamental Research Funds for the Central Universities
Subject
General Materials Science,General Chemistry
Cited by
7 articles.
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