Membrane-camouflaged supramolecular nanoparticles for co-delivery of chemotherapeutic and molecular-targeted drugs with siRNA against patient-derived pancreatic carcinoma.
10.1016/j.apsb.2022.02.007
- Author:
Honglin TANG
1
;
Yanan XUE
1
;
Bowen LI
2
;
Xiaojie XU
2
;
Fu ZHANG
1
;
Jiajing GUO
2
;
Qijun LI
1
;
Tingting YUAN
2
;
Yuan CHEN
2
;
Yubin PAN
1
;
Yuan PING
2
;
Da LI
1
Author Information
1. Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China.
2. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
- Publication Type:Journal Article
- Keywords:
Chemotherapy;
Drug antagonism;
Hybrid membrane;
Nanomedicine;
Pancreatic carcinoma;
Patient-derived tumor;
Target therapy;
siRNA
- From:
Acta Pharmaceutica Sinica B
2022;12(8):3410-3426
- CountryChina
- Language:English
-
Abstract:
Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine (GEM) with the molecular-targeted drug erlotinib (Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuli-responsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA (siRNA) for synergistic pancreatic cancer treatment. This "all-in-one" delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor (PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.
