Spatially targeting and regulating tumor-associated macrophages using a raspberry-like micellar system sensitizes pancreatic cancer chemoimmunotherapy
Ting Li, Dong Chen, Houqin Liu, Tao Yuan, Xuan He, Shuya Zang, Jiaxin Li, Ling Zhang, Man Li, Ji Liu, Qin He
Abstract
a cathepsin B (CTSB) substrate peptide to obtain raspberry-like GD@PP/Wtmn micelles. Upon arrival at the TME, GD was released in response to highly expressed CTSB, allowing deep penetration of the tumor and overcoming of the stromal barrier, while PP/Wtmn remained in the perivascular area where TAMs abundantly resided. By inhibiting the PI3K pathway, the M2-like TAMs were repolarized into M1-like TAMs and then activated antitumor immunity, further synergizing with GEM to suppress tumor growth. This tumor and TAMs dual targeting nanoplatform provides an alternative approach to sensitize chemoimmunotherapy against pancreatic cancer.
Topics & Concepts
ChemoimmunotherapyCancer researchPancreatic cancerImmunityChemistryMedicineCancerImmunotherapyImmune systemImmunologyInternal medicineImmune cells in cancerPhagocytosis and Immune RegulationNanoplatforms for cancer theranostics