Different PEG‐PLGA Matrices Influence In Vivo Optical/Photoacoustic Imaging Performance and Biodistribution of NIR‐Emitting π‐Conjugated Polymer Contrast Agents

Abstract

The π‐conjugated polymer poly[2,6‐(4,4‐bis‐(2‐ethylhexyl)‐4H‐cyclopenta[2,1‐b;3,4‐b0]‐dithiophene)‐alt‐4,7‐(2,1,3‐benzothiadiazole)] (PCPDTBT) with deep‐red/near‐infrared (NIR) absorption and emission has been investigated as a contrast agent for in vivo optical and photoacoustic imaging. PCPDTBT is encapsulated within poly(ethylene glycol) methyl ether‐block‐poly(lactide‐co‐glycolide) (PEG2kDa–PLGA4kDa or PEG5kDa–PLGA55kDa) micelles or enveloped by the phospholipid, 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethylene glycol)‐2000] (PEG2kDa‐DPPE), to investigate the formulation effect on imaging performance, biodistribution, and biocompatibility. Nanoparticles that meet the quality requirements for parenteral administration are generated with similar physicochemical properties. Optical phantom imaging reveals that both PEG‐PLGA systems exhibit a 30% higher signal‐to‐background ratio (SBR) than PEG2kDa‐DPPE. This trend cannot be observed in a murine HeLa xenograft model following intravenous administration since dramatic differences in biodistribution are observed. PEG2kDa–PLGA4kDa systems accumulate more rapidly in the liver compared to other formulations and PEG2kDa‐DPPE demonstrates a higher tumor localization. Protein content in the “hard” corona differs between formulations (PEG2kDa‐DPPE < PEG2kDa–PLGA4kDa < PEG5kDa–PLGA55kDa), although this observation alone does not explain biodistribution patterns. PEG2kDa‐PLGA4kDa systems show the highest photoacoustic amplitude in a phantom, but also a lower signal in the tumor due to differences in biodistribution. This study demonstrates that formulations for conjugated polymer contrast agents can have significant impact on both imaging performance and biodistribution.

Thermal Lens Spectrometry Reveals Thermo-Optical Property Tuning of Conjugated Polymer Nanoparticles Prepared by Microfluidics

“…In addition to the size, the surface properties of nanoparticles designed for biomedical applications have an important effect on their circulation, distribution, and cellular internalization. , It is worth mentioning that PCPDTBT CPNs stabilized with both PEG 2k -PLGA 15k and PEG 5k -PLGA 55k assessed previously presented excellent biocompatibility with mammalian cells and human blood components and showed stable properties in relevant biological media . The zeta potential is related to the different material composition of a formulation, with the end groups on the nanoparticle surface influencing the charge present in each system .…”

Chemical Design of Activatable Photoacoustic Probes for Precise Biomedical Applications

“…According to the interactions between the PA contrast agent and the molecular target, contrast agent can be divided into nontargeted and targeted. Generally, nontargeted PA contrast agents refer to the imaging agents without any targeting unit, which are often used in biomedical research such as in vivo angiography, − biodistribution monitoring, − drug metabolism evaluation, ,, etc. In contrast, targeted PA contrast agents usually consist of a targeting unit such as aptamers, , antibodies, peptides, − and small-molecule ligands, − which connect with the additional PA generation components, enabling the specific readout of the biomarker or biological events in certain locations.…”

Exogenous Contrast Agents in Photoacoustic Imaging: An In Vivo Review for Tumor Imaging

“…Still, longer incubation times are required to measure blood circulation times and the use of targeting moieties for specific tissues and tumors to enhance tumor targeting abilities [ 56 , 57 ] (see Table 2 ). In general, the advantage of using conjugated polymers, aside from their NIR absorbance/emission for PAI and photothermal therapy, is the ability to modify side chains to achieve desired characteristics such as self-assembly, increased protein corona formation for better nanoparticle biodistribution and targeted applications with the band gap in their π-π* electronic transition influencing emitted spectra and leading to tunable optical properties [ 58 , 59 ].…”