Multimodal Polymer Nanoparticles with Combined ¹⁹F Magnetic Resonance and Optical Detection for Tunable, Targeted, Multimodal Imaging in Vivo

Abstract

Understanding the complex nature of diseased tissue in vivo requires development of more advanced nanomedicines, where synthesis of multifunctional polymers combines imaging multimodality with a biocompatible, tunable, and functional nanomaterial carrier. Here we describe the development of polymeric nanoparticles for multimodal imaging of disease states in vivo. The nanoparticle design utilizes the abundant functionality and tunable physicochemical properties of synthetically robust polymeric systems to facilitate targeted imaging of tumors in mice. For the first time, high-resolution (19)F/(1)H magnetic resonance imaging is combined with sensitive and versatile fluorescence imaging in a polymeric material for in vivo detection of tumors. We highlight how control over the chemistry during synthesis allows manipulation of nanoparticle size and function and can lead to very high targeting efficiency to B16 melanoma cells, both in vitro and in vivo. Importantly, the combination of imaging modalities within a polymeric nanoparticle provides information on the tumor mass across various size scales in vivo, from millimeters down to tens of micrometers.

Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date

“…Nanoparticles were introduced to decrease some of the challenges of traditional drug delivery, but come with their own difficulties and limitations that will continue to be an important area of research. In vivo bio-distribution and toxicity studies currently guide particle design and clinical trial candidates, but the real world use of nanomedicines need Phase IV post-marketing review after clinical application to show the full benefits and limitations of these technologies (11,20,(83)(84)(85)(86). Several nanomedicine products have undergone clinical trials only to be later withdrawn due to efficacy or safety concerns e.g.…”

“…Particle size, shape, and surface chemistry are key factors that determine performance criteria, including the degree of protein adsorption, cellular uptake, biodistribution patterns, and clearance mechanisms (for a detailed review, see Nel, et al, 2009 (10)). Particle size plays a key role in clearance of these materials from the body, with small particles (<10 nm) being cleared via the kidneys, and larger particles (>10 nm) being cleared through the liver and the mononuclear-phagocyte system (MPS) (11)(12)(13)(14). The desired clearance mechanism can be a factor in the design of the nanomedicine; e.g.…”

Superfluorinated PEI Derivative Coupled with 99mTc for ASGPR Targeted 19F MRI/SPECT/PA Tri‐Modality Imaging

“…Moreover, successful examples of 19 F-based probes with preeminent targeting ability are limited. [12][13][14][15] PAI agents have similar characteristics. The cytotoxicity of these agents (including nanoparticles, such as gold NPs (nano particles), carbon nanotubes, silica NPs, and polymeric NPs) is debatable and often emerges in a dose-and timedependent manner.…”

Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents

“…Recently, RAFT has been applied in synthesis of classic hyperbranched or core cross-linked star polymer nanocontrast agents, which has demonstrated good control of polymer structure. [36][37][38]44,45 The novel dimethacrylate cross-linker 6 employed incorporates the DO3A macrocycles simultaneously during the branching process ensuring the DO3A macrocycles are …”