Molecular photoacoustic imaging of breast cancer using an actively targeted conjugated polymer

Abstract

Conjugated polymers (CPs) are upcoming optical contrast agents in view of their unique optical properties and versatile synthetic chemistry. Biofunctionalization of these polymer-based nanoparticles enables molecular imaging of biological processes. In this work, we propose the concept of using a biofunctionalized CP for noninvasive photoacoustic (PA) molecular imaging of breast cancer. In particular, after verifying the PA activity of a CP nanoparticle (CP dots) in phantoms and the targeting efficacy of a folate-functionalized version of the same (folate-CP dots) in vitro, we systemically administered the probe into a folate receptor-positive (FR+ve) MCF-7 breast cancer xenograft model to demonstrate the possible application of folate-CP dots for imaging FR+ve breast cancers in comparison to CP dots with no folate moieties. We observed a strong PA signal at the tumor site of folate-CP dots-administered mice as early as 1 hour after administration as a result of the active targeting of the folate-CP dots to the FR+ve tumor cells but a weak PA signal at the tumor site of CP-dots-administered mice as a result of the passive accumulation of the probe by enhanced permeability and retention effect. We also observed that folate-CP dots produced ~4-fold enhancement in the PA signal in the tumor, when compared to CP dots. These observations demonstrate the great potential of this active-targeting CP to be used as a contrast agent for molecular PA diagnostic imaging in various biomedical applications.

Intracellular delivery and ultrasonic activation of folate receptor-targeted phase-change contrast agents in breast cancer cells in vitro

“…Folate receptor-targeted nanovehicles have been used to deliver siRNA [37] and chemotherapeutic drugs [38, 39, 40, 41, 42] intracellularly within MDA-MB-231 and MCF-7 breast cancer cells. Nanoparticles ranging from 50 – 400 nm are capable of folate receptor-mediated endocytosis [36, 37, 40, 44], which overlaps with the sizing distribution of our 1:1 DFB/OFP nanodroplet formulation used in the present study [26]. For both MDA-MB-231 and MCF-7 breast cancer cells, one hour has proven sufficient for intracellular accumulation of nanoparticles via the folate receptor pathway [34, 36].…”

“…Recent efforts to quantify folate receptor isoform expression on the surface of breast cancer cells has shown that MDA-MB-231 cells have 1.76 times more FR-α expression relative to MCF-7 cells [35]. Folate receptor-targeted nanoparticles have been investigated for magnetic resonance imaging [34] and photoacoustic imaging [36] of breast tumors. In addition to imaging agents, targeted nanoparticles can deliver gene vectors or drugs to cancer cells, thereby maximizing the therapeutic payload and limiting off-target effects.…”

Controllable Cobalt Oxide/Au Hierarchically Nanostructured Electrode for Nonenzymatic Glucose Sensing

“…The photoacoustic signal is considered inherently weak due to the low intrinsic absorption of oxyhemoglobin and deoxyhemoglobin in the NIR [177,[373][374][375]. However, high spatial resolution and enhanced sensitivity were found to accompany the use of HAuNS in the PAT experiment reported by Lu et al [177].…”

Current and Emerging Clinical Applications of Multispectral Optoacoustic Tomography (MSOT) in Oncology

“…Utilization of nanoparticles for tumor imaging plus targeted drug delivery has been investigated using numerous nanoagents containing fluorescent dyes, gold, or silver for imaging and therapeutic drug delivery vehicles (32-35). To improve tumor delivery of nanoagents to tumors it is necessary to longitudinally track their biodistribution and accumulation, especially in the reticuloendothelial system, and to increase tumor accumulation and to decrease off-target uptake.…”

“…MSOT has identified tumor specific accumulation and biodistribution of targeted gold nanorods, mesoporous silica nanoparticles and liposomes in pancreatic tumors (9-11) and polymeric nanoparticles in breast tumors (35). Evaluation of tumor specificity, biodistribution and pharmacokinetics of tumor targeted nanoparticles, in the context of orthotopic and genetically modified organisms, represents an expanding, but inadequately developed use of MSOT; however, several light-absorbing materials, i.e.…”