Surface modification of doxorubicin-loaded nanoparticles based on polydopamine with pH-sensitive property for tumor targeting therapy

Dongdong Bi,Lei Zhao,Runqi Yu,Haowen Li,Yifei Guo,Xiangtao Wang,Meihua Han

doi:10.1080/10717544.2018.1440447

Abstract

One major challenge of current surface modification of nanoparticles is the demand for chemical reactive polymeric layers, such modification is always complicated, inefficient, and may lead the polymer lose the ability to encapsulate drug. To overcome this limitation, we adopted a pH-sensitive platform using polydopamine (PDA) as a way of functionalizing nanoparticles (NPs) surfaces. All this method needed to be just a brief incubation in weak alkaline solution of dopamine, which was simple and applicable to a variety of polymer carriers regardless of their chemical reactivity. We successfully conjugated the doxorubicin (DOX)-PDA-poly (lactic-co-glycolic acid) (PLGA) NPs with two typical surface modifiers: folate (FA) and a peptide (Arg-Gly-Asp, RGD). The DOX-PDA-FA-NPs and DOX-PDA-RGD-NPs (targeting nanoparticles) were characterized by particle size, zeta potential, and surface morphology. They were quite stable in various physiological solutions and exhibited pH-sensitive property in drug release. Compared to DOX-NPs, the targeting nanoparticles possessed an excellent targeting ability against HeLa cells. In addition, the in vivo study demonstrated that targeting nanoparticles achieved a tumor inhibition rate over 70%, meanwhile prominently decreased the side effects of DOX and improve drug distribution in tumors. Our studies indicated that the DOX-PLGA-NPs modified with PDA and various functional ligands are promising nanocarriers for targeting tumor therapy.

Highlights

Cervical cancer is the most common cancer among females, especially in developing countries (Dasari et al, 2015)
The DOX-NPs were immersed in the dopamine solution to form a tight PDA surface layer
The weak alkaline condition is an essential process for oxidation of dopamine and conjugation of ligand (FA and RGD) to PDA coated NPs according to Michael addition or Schiff-base reaction (Xing et al, 2017)

Summary

Introduction

Cervical cancer is the most common cancer among females, especially in developing countries (Dasari et al, 2015). Doxorubicin (DOX), known as adriamycin (ADM) is a widely used treatment strategy for solid tumors, cervical cancer (Zhong et al, 2017a). DOX takes effect by affecting the activity of topoisomerase II and inhibiting the synthesis of DNA to suppress cell growth (both normal and cancer cells) (Czeczuga-Semeniuk et al, 2004; Pranatharthiharan et al, 2016). The serious side effects of DOX, such as myelotoxicity and cumulative cardiotoxicity, limited its therapeutic indexes (Singal et al, 1987; Crider et al, 2012). In order to solve this problem, many efforts have been devoted to enhancing the delivery of DOX to tumors (Lammers et al, 2008; Loomis et al, 2011; Mallick & Choi, 2014)

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Conclusion