Paclitaxel-loaded and folic acid-modified PLGA nanomedicine with glutathione response for the treatment of lung cancer.

Wang Yao,Jialiang Yao,Tianle Luo,Jianhui Tian,Zhanxia Zhang,Zujun Que,Fangfang Qian,Dan Zheng,Pan Yu

doi:10.1093/abbs/gmab073

Abstract

Targeted delivery and smart response of nanomedicine hold great promise for improving the therapeutic efficacy and alleviating the side effects of chemotherapy agents in cancer treatment. However, availability of only a few studies that discuss organic nanomedicines with these properties limits the development prospects of nanomedicines. In the present study, folic acid (FA)-targeted delivery and glutathione (GSH) smart responsive nanomedicine were rationally designed for paclitaxel (PTX) delivery for the treatment of lung cancer. Compared with other stimuli-responsive nanomedicines, this nanocarrier was not only sensitive to biologically relevant GSH for on-demand drug release but also biodegradable into biocompatible products after fulfilling its delivery task. The nanomedicine first entered tumor cells via FA and its receptor-mediated endocytosis. After the lysosomal escape, poly(lactic-co-glycolic acid) (PLGA) nanomedicine was triggered by a higher level of GSH and released its cargo into the tumor microenvironment. In vitro and in vivo results revealed that the PLGA nanomedicine not only inhibited the proliferation and promoted the apoptosis of lung cancer cells significantly but also possessed less toxic side effects when compared with free PTX. Therefore, the proposed drug delivery system demonstrates the potential of a multifunctional nano-platform to enhance bioavailability and reduce the side effects of chemotherapy agents.

Highlights

Lung cancer is the malignant tumor with the highest morbidity (12%~13%) and mortality (22 ~ 24%) [1, 2]
Smart responsive PTX-loaded Folic acid (FA)-modified PLGA nanomedicine for the treatment of lung cancer
The PLGA nanomedicine was stimulated by intracellular high GSH level, and anticancer agent was released for inhibiting the proliferation of lung tumor cells

Summary

Introduction

Lung cancer is the malignant tumor with the highest morbidity (12%~13%) and mortality (22 ~ 24%) [1, 2]. The main chemotherapy agents include platinum complexes, paclitaxel, doxorubicin, decitabine, etc. [4] Paclitaxel (PTX) is a secondary metabolite extracted from the bark of yew. Its toxic side effects are obvious, such as anaphylaxis from its solvent (polyoxyethylene castor oil), myelosuppression, neurotoxicity and cardiovascular toxicity, etc. [7] how to reduce PTX toxicity and side effects is an urgent problem to be solved. To reduce its toxic side effects, scientists developed a series of PTX nanomedicines, such as albumin-bound PTX (Abraxane) and liposome-entrapped PTX (LEP), etc. [8] these nanomedicines reduce the toxic side effects of PTX, a new generation of nanomedicines should have the properties of tumor microenvironmental response and targeted delivery to improve their therapeutic effect To reduce its toxic side effects, scientists developed a series of PTX nanomedicines, such as albumin-bound PTX (Abraxane) and liposome-entrapped PTX (LEP), etc. [8] these nanomedicines reduce the toxic side effects of PTX, a new generation of nanomedicines should have the properties of tumor microenvironmental response and targeted delivery to improve their therapeutic effect

Methods

Results

Conclusion