A ROS-response hyaluronic acid-coated/chitosan polymer prodrug for enhanced tumour targeting efficacy of SN38

Ethyl-10-hydroxycamptothecin (SN38) is a camptothecin derivative with significant anti-tumour therapeutic potential, while the clinical application of SN38 was limited by its poor water solubility and low stability. Herein, a core-shell polymer prodrug hyaluronic acid chitosan-S-SN38 (HA@CS-S-SN38) was designed by CS-S-SN38 as the core and the HA as the shell, which aims to overcome the limitations of the clinical application of SN38, while realising the high tumour targeting of polymer prodrug and the controllable release of drug in tumour cells. HA@CS-S-SN38 showed the high responsiveness of the tumour microenvironment and the safe stability of blood circulation. Furthermore, HA@CS-S-SN38 exhibited the begin uptake efficiency and favourable apoptosis in the 4T1 cells. More importantly, compared with irinotecan hydrochloride trihydrate (CPT-11), HA@CS-S-SN38 significantly improved the conversion efficiency of the prodrug to SN38, and showed excellent tumour targeting and retention in vivo by combining passive and active targeting strategies. In tumour-bearing mice treatment, HA@CS-S-SN38 showed the perfect anti-tumour effect and therapeutic safety. These results indicated that the polymer prodrug designed by ROS-response/HA-modification strategy is a safe and efficient drug delivery system, which provides a new idea for clinical utilisation of SN38 and warrants further evaluation.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:31

Enthalten in:

Journal of drug targeting - 31(2023), 6 vom: 14. Juli, Seite 623-633

Sprache:

Englisch

Beteiligte Personen:

Qin, Jianpeng [VerfasserIn]
Sun, Meng [VerfasserIn]
Zhen, Yanli [VerfasserIn]
Li, Ji [VerfasserIn]
Wang, Dongkai [VerfasserIn]

Links:

Volltext

Themen:

7-ethyl-10-hydroxycamptothecin
7673326042
9004-61-9
9012-76-4
Camptothecin
Chitosan
Hyaluronic Acid
Hyaluronic acid-coating
Irinotecan
Journal Article
Polymer prodrug
Polymers
Prodrugs
ROS sensitivity
Reactive Oxygen Species
Research Support, Non-U.S. Gov't
Tumour therapy
XT3Z54Z28A

Anmerkungen:

Date Completed 27.06.2023

Date Revised 27.06.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1080/1061186X.2023.2216401

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM35718890X