Folic Acid-Decorated β-Cyclodextrin-Based Poly(ε-caprolactone)-dextran Star Polymer with Disulfide Bond-Linker as Theranostic Nanoparticle for Tumor-Targeted MRI and Chemotherapy.

Huikang Yang,Liming Zhang,Nianhua Wang,Xinqing Jiang,Ruimeng Yang

doi:10.3390/pharmaceutics14010052

Huikang Yang, Liming Zhang + Show 3 more

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https://doi.org/10.3390/pharmaceutics14010052

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Abstract

β-cyclodextrin(βCD)-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, a well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)14) was synthesized via a couple reaction between βCD-based 14 arms poly(ε-caprolactone) (βCD-(PCL)14) and disulfide-containing α-alkyne dextran (alkyne-SS-Dex), and acted as theranostic nanoparticles for tumor-targeted MRI and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX), and superparamagnetic iron oxide (SPIO) particles were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to the folate receptor-mediated endocytosis process of the nanoparticles and glutathione (GSH), which triggered disulfide-bonds cleaving. Moreover, (FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO showed strong MRI contrast enhancement properties. In conclusion, folic acid-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.

Highlights

Polymeric nanoparticles have received great attention as theranostic nanoparticles with the ability to deliver drugs and contrasting agents to tumor tissue [1,2,3,4]
Nanoparticles were self-assembled from amphiphilic polymers, such as block, grafted, and star polymers in aqueous solution, where the hydrophobic inner core of the nanoparticles can be used to encapsulate a variety of hydrophobic guest molecules [9,10,11]
As Scheme 2 illustrates, folic acid-decorated β-cyclodextrin-based poly(ε-caprolactone)dextran star polymer was synthesized by combination of ring opening polymerization (ROP), a copper(I)-catalyzed azide-alkyne cycloaddition reaction, and a standard esterification between dextran and folic acid in the presence of EDCI and HOBt. (N3 )7 -βCD-(PCL)14 was obtained by the following two steps: first, the 7 primary hydroxyl groups of βCD were selectively modified into azido groups ((N3 )7 -βCD-(OH)14 ); and, second, the remaining

Summary

Introduction

Polymeric nanoparticles have received great attention as theranostic nanoparticles with the ability to deliver drugs and contrasting agents to tumor tissue [1,2,3,4]. Doxorubicin (DOX) is widely used in clinical practice, but it still has some drawbacks that need to be overcome, including poor water solubility, short residence times in circulation, and poor biodistribution. These drugs can cause serious side effects, including nausea, vomiting, cardiotoxicity, myelosuppression, mucositis, hair loss, and systemic toxicity [5,6,7,8]. Polymeric nanoparticles as drug cargo can effectively improve the water solubility and pharmacokinetics and prevent the premature burst-release of drugs, and enhance drug tumor selectivity [12,13]. 4.0/).

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