Open AccessA Space‐Time Conversion Vehicle for Programmed Multi‐Drugs Delivery into Pancreatic Tumor to Overcome Matrix and Reflux Barriers
Author(s) -
Huo Taotao,
Zhang Xiaoyi,
Qian Min,
Nie Huifang,
Liang Dong,
Lin Chenteng,
Yang Yafeng,
Guo Wei,
Lächelt Ulrich,
Huang Rongqin
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202200608
Subject(s) - extracellular matrix , drug delivery , efflux , chemistry , drug , extracellular , mesoporous silica , nanotechnology , materials science , pharmacology , cancer research , biophysics , mesoporous material , medicine , biochemistry , biology , catalysis
The numerous biological barriers, which limit pharmacotherapy of pancreatic carcinoma, including inadequate drug accumulation in the tumor environment, a dense extracellular matrix (ECM) and efficient drug‐efflux mechanisms, illustrate the requirement of multifunctional delivery systems to overcome the individual barriers at the right place at the right time. Herein, a space–time conversion vehicle based on covalent organic framework (COF)‐coated mesoporous silica nanospheres (MSN) with a sandwiched polyethyleneimine (PEI) layer (MPCP), is designed. The space‐specific drugs‐loaded vehicle (M G P P C L P) is obtained by separately incorporating a chemotherapeutic agent (gemcitabine, G) into the MSN core, a P glycoprotein inhibitor (LY 335979, P) into the PEI layer, and an extracellular matrix disruptor (losartan, L) into the COF shell. Thereafter, a programmed drug delivery is achieved via the ordered degradation from COF shell to MSN core. Sequential release of the individual drugs, synergized with a change of nanoparticle surface charge, contribute to an obvious extracellular matrix distraction, distinct drug efflux inhibition, and consequently enhance chemotherapeutic outcomes in pancreatic carcinoma. This MPCP‐based vehicle design suggests a robust space–time conversion strategy to achieve programmed multi‐drugs delivery and represents a new avenue to the treatment of pancreatic carcinoma by overcoming extracellular matrix and drug reflux barriers.