A chemotherapeutic self-sensibilized drug carrier delivering paclitaxel for the enhanced chemotherapy to human breast MDA-MB-231 cells

Lingli Zhang; Chengguang Wu; Shansong Mu; Wei Xue; Dong Ma

doi:10.1016/j.colsurfb.2019.06.052

A chemotherapeutic self-sensibilized drug carrier delivering paclitaxel for the enhanced chemotherapy to human breast MDA-MB-231 cells

Colloids Surf B Biointerfaces. 2019 Sep 1:181:902-909. doi: 10.1016/j.colsurfb.2019.06.052. Epub 2019 Jun 24.

Authors

Lingli Zhang¹, Chengguang Wu¹, Shansong Mu², Wei Xue¹, Dong Ma³

Affiliations

¹ Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China.
² Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China. Electronic address: tmuss@jnu.edu.cn.
³ Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China. Electronic address: tmadong@jnu.edu.cn.

PMID: 31382339
DOI: 10.1016/j.colsurfb.2019.06.052

Abstract

To enhance the chemotherapy effect to MDA-MB-231, a glutathione (GSH)-sensitive amphiphilic hyperbranched poly (amide-amine) (mPEG-PLGA-HPAA) was synthesized, and the anti-cancer drug, paclitaxel (PTX) was then encapsulated into the mPEG-PLGA-HPAA micelles. The mPEG-PLGA-HPAA containing a large number of disulfide bonds could degrade and then consume the GSH intracellularly, which was expected to enhances the sensitivity of MDA-MB-231 cells to PTX. It was found that the mPEG-PLGA-HPAA/PTX nanoparticles could respond to the GSH and showed a GSH-controlled PTX release. Simultaneously, the mPEG-PLGA-HPAA/PTX nanoparticles significantly enhanced the efficacy of PTX by inhibiting MDA-MB-231 cells proliferation and inducing cells apoptosis, performing the self-sensitization effect of chemotherapy. Moreover, the drug carrier of mPEG-PLGA-HPAA exhibited excellent biocompatibility in vitro and in vivo. These results indicated that the self-sensitized drug carrier is a promising route to maximize the therapeutic effect and minimize the side effects of chemotherapy drugs used currently in clinical.

Keywords: Drug delivery; Hyperbranched poly (amide amine); Redox; Self-sensitization.

MeSH terms

Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Drug Carriers / chemical synthesis
Drug Carriers / chemistry
Drug Delivery Systems*
Drug Screening Assays, Antitumor
HEK293 Cells
Humans
Molecular Structure
Paclitaxel / chemistry
Paclitaxel / pharmacology*
Particle Size
Polyamines / chemical synthesis
Polyamines / chemistry*
Polyesters / chemical synthesis
Polyesters / chemistry*
Polyethylene Glycols / chemical synthesis
Polyethylene Glycols / chemistry*
Surface Properties
Surface-Active Agents / chemical synthesis
Surface-Active Agents / chemistry*

Substances

Antineoplastic Agents, Phytogenic
Drug Carriers
Poly(amidoamine)
Polyamines
Polyesters
Surface-Active Agents
methoxypolyethyleneglycol-poly(lactic-co-glycolic acid)
Polyethylene Glycols
Paclitaxel