Co-Delivery of Paclitaxel Prodrug, Gemcitabine and Porphine by Micelles for Pancreatic Cancer Treatment via Chemo-Photodynamic Combination Therapy.

Content Provider	Europe PMC
Author	Wu, Qiwei Ma, Xiaodong Zhou, Wenhui Yu, Rong Rosenholm, Jessica M. Tian, Weizhong Zhang, Lirong Wang, Dongqing Zhang, Hongbo
Editor	Kachrimanis, Kyriakos Medarevic, Djordje
Copyright Year	2022
Abstract	Pancreatic carcinoma is an aggressive subtype of cancer with poor prognosis, known for its refractory nature. To address this challenge, we have established a stable nanoplatform that combines chemotherapy with photodynamic therapy (PDT) to achieve better curative efficacy. First, we designed and synthesized a disulfide-bonded paclitaxel (PTX)-based prodrug, which was further mixed with gemcitabine (GEM) and photosensitizer THPP in an optimized ratio. Subsequently, the mixture was added dropwise into amphiphilic polymer DSPE-PEG water solution to form micelles composed of DSPE-PEG nanoparticles (TPG NPs). The TPG NPs were around 135 nm, and showed great ability of DTT stimulated release of PTX and GEM. Moreover, the TPG NPs can be efficiently uptaken by pancreatic cancer PANC-1 cells and effectively kill them, especially when combined with 650 nm laser irradiation. Finally, the TPG NPs have shown enhanced long-term circulation ability and also exhibited efficient anti-tumor activity in combination with 650 nm laser irradiation in a pancreatic cancer mouse model. In summary, the designed TPG NPs possesses great potential for co-delivery of paclitaxel prodrug, GEM and THPP, which enables combined chemo-photodynamic therapy for cancer treatment. In addition, the stimulated release of PTX prodrug and GEM also allows for better targeting of tumor cells and the increased therapeutic effect against cancer cells. Overall, the TPG NPs can serve as a good candidate for pancreatic cancer treatment.
Journal	Pharmaceutics
Volume Number	14
PubMed Central reference number	PMC9698062
Issue Number	11
PubMed reference number	36365099
e-ISSN	19994923
DOI	10.3390/pharmaceutics14112280
Language	English
Publisher	MDPI
Publisher Date	2022-10-25
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2022 by the authors.
Subject Keyword	photodynamic therapy prodrug combination therapy pancreatic carcinoma
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science