Fabrication of pH-responsive PLGA(UCNPs/DOX) nanocapsules with upconversion luminescence for drug delivery

Junwei Zhao,Jili Li,Hui Yang,Yujiang Wang,Xin Wang

doi:10.1038/s41598-017-16948-4

Abstract

The integration of anticancer drugs and inorganic nanocrystals in polymer nanocapsules is a widely used strategy to improve their functionality, stability and sustained release. However, the complexity in the preparation of functional nanocapsules and their reproducibility still challenge these promising drug carriers in clinical application. Here we introduce a simple one-step self-assembly strategy to prepare multifunctional nanocapsules based on simultaneous poly (DL-lactic-co-glycolic acid) (PLGA) encapsulation of antitumor drug doxorubicin hydrochloride (DOX) and NaYF4:Yb,Er@NaGdF4 upconversion nanoparticles (UCNPs) for cancer cell imaging and drug delivery. The obtained PLGA(UCNPs/DOX) nanocapsules with a small size of ≈150 nm possessed bright upconversion fluorescence and could act as T1-weighted contrast agents for magnetic resonance imaging (MRI). Moreover, the PLGA(UCNPs/DOX) nanocapsules exhibited pH-responsive drug releasing behavior, causing the loaded DOX easily releasing at cancer cells, and an obvious cytotoxicity via MTT assay. The endocytosis process of PLGA (UCNPs/DOX) nanocapsules is evaluated using optical microscopy and upconversion fluorescence microscopy. These results demonstrated that the developed PLGA nanocapsules could serve as multifunctional drug delivery systems for cancer imaging and therapy.

Highlights

Multifunctional nanocomposites that would simultaneously possess diagnosis, target and therapy function have attracted much attention for cancer treatment and tumor suppression[1]
The PLGA nanocapsules successfully encapsulating the inorganic nanocrystals as imaging agents and chemotherapeutic drug (DOX) were prepared by an oil-in-water (O/W) emulsion method and a subsequent solvent evaporation followed by polymer solidification at room temperature
The hydrophobic DOX and NaYF4:Yb,Er@NaGdF4 NPs were incorporated into the hydrophobic domain of PLGA molecules via hydrophobic interaction, and the PLGA vesicles were generated in the presence of poly(vinyl alcohol) (PVA) emulsifier

Summary

Introduction

Multifunctional nanocomposites that would simultaneously possess diagnosis, target and therapy function have attracted much attention for cancer treatment and tumor suppression[1]. The design of specific stimuli-responsive systems is prospective since the anticancer drugs are stable during delivery and may be released at the targeted cells in response to external stimuli such as temperature, light irradiation, redox reagents, pH, enzymes, and ionic strength[2,3,4,5,6,7,8,9,10,11] Among these “smart” carriers, a pH-responsive system for encapsulating anti-tumor drugs has been a hot research topic in view of the fact that the interstitial fluids of many solid tumors have lower pH values in contrast to the surrounding normal tissue[12,13,14]. We developed a simple one-step self-assembly strategy to prepare multifunctional PLGA nanocapsules, which incorporated simultaneously with anti-tumor drug DOX and NaYF4:Yb,Er@NaGdF4 UCNPs as MRI and fluorescence imaging agents, for bioimaging and drug delivery. The in vitro cytotoxic effects of the PLGA(UCNPs/DOX) nanocapsules were evaluated in H460 cancer cells

Methods

Results

Conclusion