1. Intelligent micelles for on-demand drug delivery targeting extracellular matrix of pancreatic cancer.
- Author
-
Li C, Chen Q, and Jiang C
- Subjects
- Animals, Humans, Cell Line, Tumor, Carcinoma, Pancreatic Ductal drug therapy, Carcinoma, Pancreatic Ductal pathology, Silybin administration & dosage, Silybin pharmacology, Mice, Nude, Tumor Microenvironment drug effects, Mice, Inbred BALB C, Hyaluronan Receptors metabolism, Antineoplastic Agents administration & dosage, Antineoplastic Agents therapeutic use, Antineoplastic Agents pharmacokinetics, Micelles, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology, Gemcitabine, Deoxycytidine analogs & derivatives, Deoxycytidine administration & dosage, Deoxycytidine pharmacokinetics, STAT3 Transcription Factor antagonists & inhibitors, STAT3 Transcription Factor metabolism, Hyaluronic Acid chemistry, Extracellular Matrix metabolism, Drug Liberation, Drug Delivery Systems
- Abstract
As a key pathological feature of pancreatic ductal adenocarcinoma(PDAC), the dense extracellular matrix(ECM) limits the penetration of chemotherapy drugs and is involved in the formation of immunosuppressive microenvironment. Meanwhile, clinical practice has shown that the treatment strategy for ECM should consider its restriction of tumor cell metastasis, and the need for in-depth chemotherapy without destroying ECM is proposed. STAT3 inhibitors have been reported to regulate tumor microenvironment including interrupt the form of ECM. Therefore, we designed and established a micelle system MP@HA with in vivo targeting and responsive drug release function co-loading gemcitabine monophosphate and STAT3 inhibitor silibinin. The hyaluronic acid on the surface of the micelle can bind specifically to the CD44 molecule on the surface of tumor cells and help micelles accumulate at the tumor site. The nitroimidazole used to modify the polymeric skeleton can make the micellar structure collapse in response to hypoxia reduction conditions in the tumor environment, and release silibinin to widely regulate STAT3 molecules in the PDAC microenvironment. The polymer fragment attached with gemcitabine monophosphate can penetrate deep into PDAC tumors due to its small size and positive charge exposed, achieving deep chemotherapy. This research indicates a promising micelle system meeting complicated demands proposed in PDAC treatment to improve antitumor efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF