Nanoparticle-based theranostic agents

Abstract

Theranostic nanomedicine is emerging as a promising therapeutic paradigm. It takes advantage of the high capacity of nanoplatforms to ferry cargo and loads onto them both imaging and therapeutic functions. The resulting nanosystems, capable of diagnosis, drug delivery and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine, and much research effort has been devoted toward that goal. A convenience in constructing such function-integrated agents is that many nanoplatforms are already, themselves, imaging agents. Their well-developed surface chemistry makes it easy to load them with pharmaceutics and promote them to be theranostic nanosystems. Iron oxide nanoparticles, quantum dots, carbon nanotubes, gold nanoparticles and silica nanoparticles, have been previously well investigated in the imaging setting and are candidate nanoplatforms for building up nanoparticle-based theranostics. In the current article, we will outline the progress along this line, organized by the category of the core materials. We will focus on construction strategies and will discuss the challenges and opportunities associated with this emerging technology.

Introduction

The term “theranostics” was coined to define ongoing efforts in clinics to develop more specific, individualized therapies for various diseases, and to combine diagnostic and therapeutic capabilities into a single agent [1]. The rationale arose from the fact that diseases, such as cancers, are immensely heterogeneous, and all existing treatments are effective for only limited patient subpopulations and at selective stages of disease development [2]. The hope was that a close marriage of diagnosis and therapeutics could provide therapeutic protocols that are more specific to individuals and, therefore, more likely to offer improved prognoses.

The emergence of nanotechnology has offered an opportunity to draw diagnosis and therapy closer [3]. Nanoparticle (NP)-based imaging and therapy have been investigated separately, and understanding of them has now evolved to a point enabling the birth of NP-based theranostics, which can be defined as nanoplatforms that can co-deliver therapeutic and imaging functions. This is in a way an extension of the traditional theranostics but focusing more on “co-delivery”. It adds to the previous paradigm for allowing imaging to be performed not only before or after, but also during a treatment regimen. It is convenient that many nanomaterials are already imaging agents and can be readily “upgraded” to theranostic agents by mounting therapeutic functions on them. One underlying driving force of such a combination is that imaging and therapy both require sufficient accumulation of agents in diseased areas. This common targeting requirement brings the two research domains closer and, ultimately, will blur the boundary between them, since many techniques to enhance imaging can, at least in theory, be readily transferred to the therapeutic domain, and vice versa.

Targeting strategies can be varied immensely to suit the desired targets. In the case of cancer, it is a common approach to identify a biomarker that is aberrantly expressed on the surface of cancer cells, and then to load its cognate binding vector onto probes/carriers to achieve recognition and tumor homing [4]. For nanoplatforms, the unique size scale of the particles enables achievement of an enhanced-permeability-and-retention (EPR) effect in tumor targeting [5]. In all efforts, however, care has to be taken with the particles' surfaces to avoid innate immunosystem recognition and to secure sufficiently long circulation half lives for the agents to reach their targets.

Nanoparticle-based imaging and therapy are each struggling to advance into clinical trials and, as descendants of the two, nanoparticle-based theranostics are still in their early stages of development. However, the push provided by advances in nanotechnology and the call for personalized medicine have already made nanoparticle-based theranostics a research hotspot. This review attempts to give a summary of the efforts made so far along this line. We will introduce theranostic agents, arranged by the category of their core nanomaterial, that hold potential in the theranostic setting. The techniques used to form linkage between nanoplatforms and functionally entities have been well developed and are summarized in Table 1. As mentioned above, most of the nanoplatforms to be described here already perform imaging functions and have been widely investigated for imaging related applications. However, imaging alone, without therapy, will not be the focus of this article, and readers are referred to several excellent reviews on that topic [5], [6], [7], [8]. Instead, we will focus on the buildup and application of theranostic agents, as well as the associated surface coating and coupling chemistry that may affect transport, delivery and release of cargos.