Novel multi-stimuli responsive functionalized PEG-based co-delivery nanovehicles toward sustainable treatments of multidrug resistant tumor

Jingwen Xu; Xiangji Yan; Xin Ge; Mingzhen Zhang; Xugang Dang; Yan Yang; Feng Xu; Yanling Luo; Guoliang Li

doi:10.1039/d0tb02192j

Novel multi-stimuli responsive functionalized PEG-based co-delivery nanovehicles toward sustainable treatments of multidrug resistant tumor

Jingwen Xu
, Xiangji Yan
, Xin Ge
, Mingzhen Zhang
, Xugang Dang
, Yan Yang
, Feng Xu
, Yanling Luo
, Guoliang Li

Health Science Center

Shaanxi University of Science and Technology
Xi'an Jiaotong University
University of Science and Technology of China
Shaanxi Normal University

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

The efficacy of ongoing anticancer treatment is often compromised by some barriers, such as low drug content, nonspecific release of drug delivery system, and multidrug resistance (MDR) effect of tumors. Herein, in the research a novel functionalized PEG-based polymer cystine-(polyethylene glycol)₂-b-(poly(2-methacryloyloxyethyl ferrocenecarboxylate)₂) (Cys-(PEG₄₅)₂-b-(PMAOEFC)₂) with multi-stimuli sensitive mechanism was constructed, in which doxorubicin (DOX) was chemical bonded through Schiff base structure to provide acid labile DOX prodrug (DOX)₂-Cys-(PEG₄₅)₂-b-(PMAOEFC)₂. Afterwards, paclitaxel (PTX) and its diselenide bond linked PTX dimer were encapsulated into the prodrug through physical loading, to achieve pH and triple redox responsive (DOX)₂-Cys-(PEG₄₅)₂-b-(PMAOEFC)₂^@PTXand (DOX)₂-Cys-(PEG₄₅)₂-b-(PMAOEFC)₂^@PTX dimerwith ultrahigh drugs content. The obtained nanovehicles could self-assemble into globular micelles with good stability based on fluorescence spectra and TEM observation. Moreover, there was a remarkable “reassembly-disassembly” behavior caused by phase transition of micelles under the mimic cancerous physiological environment. DOX and PTX could be on-demand released in acid and redox stress mode, respectively. Meanwhile,in vivoanticancer studies revealed the significant tumor inhibition of nanoformulas. This work offered facile strategies to fabricate drug nanaovehicles with tunable drug content and types, it has a profound significance in overcoming MDR effect, which provided more options for sustainable cancer treatment according to the desired drug dosage and the stage of tumor growth.

Original language	English
Pages (from-to)	1297-1314
Number of pages	18
Journal	Journal of Materials Chemistry B
Volume	9
Issue number	5
DOIs	https://doi.org/10.1039/d0tb02192j
State	Published - 7 Feb 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1039/d0tb02192j

Cite this

@article{da5828a5db9e4957b374c5cbaf8a6549,

title = "Novel multi-stimuli responsive functionalized PEG-based co-delivery nanovehicles toward sustainable treatments of multidrug resistant tumor",

abstract = "The efficacy of ongoing anticancer treatment is often compromised by some barriers, such as low drug content, nonspecific release of drug delivery system, and multidrug resistance (MDR) effect of tumors. Herein, in the research a novel functionalized PEG-based polymer cystine-(polyethylene glycol)2-b-(poly(2-methacryloyloxyethyl ferrocenecarboxylate)2) (Cys-(PEG45)2-b-(PMAOEFC)2) with multi-stimuli sensitive mechanism was constructed, in which doxorubicin (DOX) was chemical bonded through Schiff base structure to provide acid labile DOX prodrug (DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2. Afterwards, paclitaxel (PTX) and its diselenide bond linked PTX dimer were encapsulated into the prodrug through physical loading, to achieve pH and triple redox responsive (DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2@PTXand (DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2@PTX dimerwith ultrahigh drugs content. The obtained nanovehicles could self-assemble into globular micelles with good stability based on fluorescence spectra and TEM observation. Moreover, there was a remarkable “reassembly-disassembly” behavior caused by phase transition of micelles under the mimic cancerous physiological environment. DOX and PTX could be on-demand released in acid and redox stress mode, respectively. Meanwhile,in vivoanticancer studies revealed the significant tumor inhibition of nanoformulas. This work offered facile strategies to fabricate drug nanaovehicles with tunable drug content and types, it has a profound significance in overcoming MDR effect, which provided more options for sustainable cancer treatment according to the desired drug dosage and the stage of tumor growth.",

author = "Jingwen Xu and Xiangji Yan and Xin Ge and Mingzhen Zhang and Xugang Dang and Yan Yang and Feng Xu and Yanling Luo and Guoliang Li",

note = "Publisher Copyright: {\textcopyright} The Royal Society of Chemistry 2021.",

year = "2021",

month = feb,

day = "7",

doi = "10.1039/d0tb02192j",

language = "英语",

volume = "9",

pages = "1297--1314",

journal = "Journal of Materials Chemistry B",

issn = "2050-750X",

publisher = "Royal Society of Chemistry",

number = "5",

}

TY - JOUR

T1 - Novel multi-stimuli responsive functionalized PEG-based co-delivery nanovehicles toward sustainable treatments of multidrug resistant tumor

AU - Xu, Jingwen

AU - Yan, Xiangji

AU - Ge, Xin

AU - Zhang, Mingzhen

AU - Dang, Xugang

AU - Yang, Yan

AU - Xu, Feng

AU - Luo, Yanling

AU - Li, Guoliang

PY - 2021/2/7

Y1 - 2021/2/7

N2 - The efficacy of ongoing anticancer treatment is often compromised by some barriers, such as low drug content, nonspecific release of drug delivery system, and multidrug resistance (MDR) effect of tumors. Herein, in the research a novel functionalized PEG-based polymer cystine-(polyethylene glycol)2-b-(poly(2-methacryloyloxyethyl ferrocenecarboxylate)2) (Cys-(PEG45)2-b-(PMAOEFC)2) with multi-stimuli sensitive mechanism was constructed, in which doxorubicin (DOX) was chemical bonded through Schiff base structure to provide acid labile DOX prodrug (DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2. Afterwards, paclitaxel (PTX) and its diselenide bond linked PTX dimer were encapsulated into the prodrug through physical loading, to achieve pH and triple redox responsive (DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2@PTXand (DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2@PTX dimerwith ultrahigh drugs content. The obtained nanovehicles could self-assemble into globular micelles with good stability based on fluorescence spectra and TEM observation. Moreover, there was a remarkable “reassembly-disassembly” behavior caused by phase transition of micelles under the mimic cancerous physiological environment. DOX and PTX could be on-demand released in acid and redox stress mode, respectively. Meanwhile,in vivoanticancer studies revealed the significant tumor inhibition of nanoformulas. This work offered facile strategies to fabricate drug nanaovehicles with tunable drug content and types, it has a profound significance in overcoming MDR effect, which provided more options for sustainable cancer treatment according to the desired drug dosage and the stage of tumor growth.

AB - The efficacy of ongoing anticancer treatment is often compromised by some barriers, such as low drug content, nonspecific release of drug delivery system, and multidrug resistance (MDR) effect of tumors. Herein, in the research a novel functionalized PEG-based polymer cystine-(polyethylene glycol)2-b-(poly(2-methacryloyloxyethyl ferrocenecarboxylate)2) (Cys-(PEG45)2-b-(PMAOEFC)2) with multi-stimuli sensitive mechanism was constructed, in which doxorubicin (DOX) was chemical bonded through Schiff base structure to provide acid labile DOX prodrug (DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2. Afterwards, paclitaxel (PTX) and its diselenide bond linked PTX dimer were encapsulated into the prodrug through physical loading, to achieve pH and triple redox responsive (DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2@PTXand (DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2@PTX dimerwith ultrahigh drugs content. The obtained nanovehicles could self-assemble into globular micelles with good stability based on fluorescence spectra and TEM observation. Moreover, there was a remarkable “reassembly-disassembly” behavior caused by phase transition of micelles under the mimic cancerous physiological environment. DOX and PTX could be on-demand released in acid and redox stress mode, respectively. Meanwhile,in vivoanticancer studies revealed the significant tumor inhibition of nanoformulas. This work offered facile strategies to fabricate drug nanaovehicles with tunable drug content and types, it has a profound significance in overcoming MDR effect, which provided more options for sustainable cancer treatment according to the desired drug dosage and the stage of tumor growth.

UR - https://www.scopus.com/pages/publications/85100843612

U2 - 10.1039/d0tb02192j

DO - 10.1039/d0tb02192j

M3 - 文章

C2 - 33443252

AN - SCOPUS:85100843612

SN - 2050-750X

VL - 9

SP - 1297

EP - 1314

JO - Journal of Materials Chemistry B

JF - Journal of Materials Chemistry B

IS - 5

ER -

Novel multi-stimuli responsive functionalized PEG-based co-delivery nanovehicles toward sustainable treatments of multidrug resistant tumor

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this