当前位置： SCI文献检索 > LIFE SCIENCES期刊下所有文献 > Codelivery of STAT3 and PD-L1 siRNA by hyaluronate-TAT trimethyl/thiolated chitosan nanoparticles suppresses cancer progression in tumor-bearing mice.

Codelivery of STAT3 and PD-L1 siRNA by hyaluronate-TAT trimethyl/thiolated chitosan nanoparticles suppresses cancer progression in tumor-bearing mice.

Abstract：

:Immunotherapy methods using potential tumor microenvironment modulators have elicited durable therapeutic responses in cancer treatment. Immune checkpoint molecule programmed cell death-ligand 1 (PD-L1) and oncogenic transcription factor STAT3 (signal transducer and activator of transcription-3) assigned as inhibitory targets of our study and particular delivery system designed to deliver small interfering RNAs (siRNAs) to silence the targeted genes. Generated trimethyl chitosan (TMC) and thiolated chitosan (TC) nanoparticles (NPs) conjugated with HIV-1-derived TAT peptide and HA (hyaluronic acid) exhibited eligible physicochemical characteristics, notable siRNA encapsulation, serum stability, non-toxicity, controlled siRNA release, and extensive cellular uptake by cancer cells. Dual inhibition with STAT3/PD-L1 siRNA-loaded HA-TAT-TMC-TC NPs led to promising results, including significant downregulation of PD-L1 and STAT3 genes, striking suppressive effects on proliferation, migration, and angiogenesis of breast and melanoma cancer cell lines, and restrained tumor growth in vivo. These findings infer the capability of HA-TAT-TMC-TC NPs containing STAT3/PD-L1 siRNAs as a novel tumor-suppressive candidate in cancer treatment.

journal_name

Life Sci

journal_title

Life sciences

authors

Bastaki S,Aravindhan S,Ahmadpour Saheb N,Afsari Kashani M,Evgenievich Dorofeev A,Karoon Kiani F,Jahandideh H,Beigi Dargani F,Aksoun M,Nikkhoo A,Masjedi A,Mahmoodpoor A,Ahmadi M,Dolati S,Namvar Aghdash S,Jadidi-Niaragh F

doi

10.1016/j.lfs.2020.118847

subject

Has Abstract

pub_date

2021-02-01 00:00:00

pages

118847

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(20)31600-3

journal_volume

266

pub_type

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