Toxicity and therapy of cisplatin-loaded EGF modified mPEG-PLGA-PLL nanoparticles for SKOV3 cancer in mice

Yunfei Wang; Peifeng Liu; Lihua Qiu; Ying Sun; Mingjie Zhu; Liying Gu; Wen Di; Yourong Duan

doi:10.1016/j.biomaterials.2012.12.033

Toxicity and therapy of cisplatin-loaded EGF modified mPEG-PLGA-PLL nanoparticles for SKOV3 cancer in mice

Biomaterials. 2013 May;34(16):4068-4077. doi: 10.1016/j.biomaterials.2012.12.033. Epub 2013 Mar 5.

Authors

Yunfei Wang¹, Peifeng Liu², Lihua Qiu¹, Ying Sun², Mingjie Zhu², Liying Gu¹, Wen Di³, Yourong Duan⁴

Affiliations

¹ Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Focus Construction Subject of Shanghai Education Department, Shanghai 200127, PR China.
² Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, PR China.
³ Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Focus Construction Subject of Shanghai Education Department, Shanghai 200127, PR China. Electronic address: [email protected].
⁴ Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, PR China. Electronic address: [email protected].

PMID: 23480957
DOI: 10.1016/j.biomaterials.2012.12.033

Abstract

Construction on the nanoparticles with lower toxicity and specific tumor targeting properties is challenging and requires careful design of composition, size, physicochemical properties tailored for the nanoparticles. Here the epidermal growth factor (EGF) modified methoxy polyethylene glycol-polylactic-co-glycolic acid-polylysine (mPEG-PLGA-PLL) encapsulated cisplatin (CDDP) nanoparticles (CDDP-NPs-EGF) was prepared to for solving the toxicity of CDDP and improving therapeutic efficiency. The remarkable features of CDDP-NPs-EGF are increasing cytotoxicity that attribute to effective cell cycle arrest and high cell apoptosis in vitro. In vivo, the CDDP-NPs-EGF change drug distribution, decrease the nephrotoxicity of CDDP and improve significantly therapeutic efficiency without inducing obvious system toxicity, verifying its key role of the CDDP-NPs-EGF in lowering drug toxicity and enhancing the antitumor efficiency for SKOV3 cancer in mice.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Apoptosis / drug effects
Cell Cycle / drug effects
Cell Death / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Cisplatin / pharmacology
Cisplatin / therapeutic use*
Epidermal Growth Factor / pharmacology*
Female
Flow Cytometry
Humans
Mice
Microscopy, Confocal
Nanoparticles / toxicity*
Nanoparticles / ultrastructure
Ovarian Neoplasms / drug therapy*
Ovarian Neoplasms / pathology
Polyesters / chemistry*
Polyethylene Glycols / chemistry*
Polylysine / chemistry*
Tissue Distribution / drug effects
Treatment Outcome
Xenograft Model Antitumor Assays

Substances

Antineoplastic Agents
Polyesters
methoxypolyethyleneglycol-poly(lactic-co-glycolic acid)
Polylysine
Polyethylene Glycols
Epidermal Growth Factor
Cisplatin