Janus nanoparticles: New generation of multifunctional nanocarriers in drug delivery, bioimaging and theranostics

Highlights

• Janus nanoparticles (JNPs) are colloidal dispersions with anisotropic nature.

• Masking, self-assembly, sputtering and microfluidics are used for JNPs synthesis.

• JNPs incorporates both hydrophobic and hydrophilic drugs simultaneously.

• JNPs are elaborately modified for molecular targeting and stimuli-responsiveness.

• JNPs are envisioned for theranostic applications in era of personalized medicine.

Abstract

Janus nanoparticles (JNPs) are anisotropic particles composed of two distinct sides with differences in chemical nature and/or polarity on each side. These particles have attracted much attention in recent years due to their dual functionality, anisotropic nature and potential applications in material science and biomedicine such as nanocorals, micro/nanomotors, catalyst, and stabilizers. With the presence of different functional group and various chemical compounds on each side, JNPs can simultaneously be modified for specific needs in drug delivery, such as loading two drugs, grafting with a targeting ligand and imaging agents. Moreover, the site-selective modification of each face allows combining different agents within a single particle without significant interaction, leading to their versatile usage in theranostics. This review discusses the main strategies used for synthesizing JNPs with controllable morphology in a wide range of sizes and surface functionality by highlighting JNPs important properties and applications in the field of drug delivery with a focus on theranostics.

Introduction

The term ‘Janus’ comes from an ancient Roman god, who has two different faces on both sides of his head [1]. Janus nanoparticles (JNPs) refer to anisotropic nanoparticles that are a combination of two distinct sides with differences in polarity and/or chemical nature [2]. Generally, there are two main groups of JNPs: patchy particles (particle with anisotropic on the surface) and compartmented particles (particle with anisotropic in composition and multiple eccentric phase-separated domains [3] (Fig. 1). Depending on the synthesis strategies, JNPs can be made from organic, inorganic and metallic materials [4]. Moreover, JNPs can be amphiphilic (If one hemisphere is hydrophilic and the other hydrophobic) or dipolar (if one hemisphere is negative charge and the other is positive charge), or they might possess other asymmetric properties. Due to different composition or surface functional groups, JNPs might also have asymmetric complex structures. Its various shapes have been synthesized, such as: simple sphere, di? ;erent kinds of dumbbell shape, vesicles/capsules and other anisotropic architectures as cylindrical or disk like. The most common structures of JNP’s are spherical shapes, commonly with one hydrophobic half and the other hydrophilic half [5].

Compared with homogenous nanoparticles, the beauty of JNPs is that these nanoparticles are asymmetric and as a single particle, have di? ;erent chemical or physical properties [6]. The homogenous nanoparticles enable co-delivery of two hydrophobic or two hydrophilic drugs while the complex JNPs can simultaneously encapsulate both hydrophobic and hydrophilic drugs [7,8]. This ability allows them to simultaneously deliver and release dissimilar drugs for producing synergistic effects at the target site. Anisotropic JNPs also have further advantages in drug delivery. Their large surface to volume ratio can be used for asymmetric optimization of various targeting ligands. They also be made of separate compartments for incorporation of imaging agents to enable real-time tracking of treatment. Since they have complex geometries, they can prevent initial contact with macrophages, allowing them to evade fast clearance by the reticuloendothelial system [7]; hence, JNPs can exhibit a desired pharmacokinetics, body distribution and pharmacodynamics. Therefore, due to its features and amphiphilicity properties, JNPs can act as multifunctional carriers, making them a promising tool in the field of drug delivery. Recently, many researches were conducted on the delivery of doxorubicin (DOX) [7,8], 6-mercaptopurine (6-MP) [9], paclitaxel [8,10], and curcumin [7] by JNPs. Moreover, these new nanoparticles can be used as "theranostic carriers” to concurrently diagnose and treat diseases. Although this can be achieved by a homogenous nanoparticle, it is difficult for two main reasons: First, sometimes drugs and diagnostic agents have different solubility; hence, the homogenous nanoparticles are not suitable for encapsulating both payloads. Second, mixing payloads with different physiochemical properties might cause complexity of the released profile [[11], [12], [13], [14]].

In this review, we introduced an overview of JNPs, discussed their synthesis methods, and went over the recent JNPs synthesis publications as well as their applications with focus on drug delivery, bioimaging, especially theranostics for the first time.