Tumor Microenvironment Stimuli-Responsive Polymeric Prodrug Micelles for Improved Cancer Therapy

PURPOSE: The discovery of nano drug delivery system has rendered a great hope for improving cancer therapy. However, there are some inevitable obstacles that constrain its development, such as the physical and biological barriers, the toxicity of carrier materials and the physiological toxicity of drugs. Here, we report a polymeric prodrug micelle (PPM) with pH/redox dual-sensitivity, which was prepared using methoxy poly (ethylene glycol) (mPEG) with favorable biosafety to improve cancer therapy.

METHOD: The tumor microenvironment stimuli-responsive PPMs were prepared and characterized in vitro and in vivo.

RESULTS: Our data displayed that the PPMs with excellent biocompatibility exhibited the stimuli-responsive drug release behavior under the microenvironment of cancer cells, superior cellular internalization and lower cytotoxicity. A new method to control drug release behavior was proposed by comparing the release behavior of PPMs formed by PEG of different molecular weight. Furthermore, the fabricated PPMs exhibited the "oral-like" blood concentration curve, improved biodistribution, reduced tissue toxicity and excellent antitumor efficiency in vivo. Consistently, these results indicated that PPMs improved chemotherapeutic efficiency and reduced side effects of the model drug doxorubicin (DOX).

CONCLUSION: The prepared pH/redox dual-sensitive PPM enhanced the chemotherapy effect on the tumor site while reducing the physiological toxicity of DOX. Graphical Abstract.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:37

Enthalten in:

Pharmaceutical research - 37(2019), 1 vom: 10. Dez., Seite 4

Sprache:

Englisch

Beteiligte Personen:

Zhang, Zhiqiang [VerfasserIn]
Yu, Miao [VerfasserIn]
An, Tong [VerfasserIn]
Yang, Jun [VerfasserIn]
Zou, Meijuan [VerfasserIn]
Zhai, Yinglei [VerfasserIn]
Sun, Wei [VerfasserIn]
Cheng, Gang [VerfasserIn]

Links:

Volltext

Themen:

3WJQ0SDW1A
80168379AG
9004-74-4
Antineoplastic Agents
Controlled release
Delayed-Action Preparations
Doxorubicin
Drug Carriers
Journal Article
Micelles
Monomethoxypolyethylene glycol
PH/redox dual-sensitive
Polyethylene Glycols
Polymeric prodrug
Prodrugs
Stimuli-responsive

Anmerkungen:

Date Completed 15.01.2020

Date Revised 17.03.2020

published: Electronic

Citation Status MEDLINE

doi:

10.1007/s11095-019-2709-1

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM30424399X