Rational Design of NIR-II Emitting Conjugated Polymer Derived Nanoparticles for Image-Guided Cancer Interventions.

Due to the reduced absorption, light scattering, and tissue autofluorescence in the NIR-II (1000-1700 nm) region, significant efforts are underway to explore diverse material platforms for in vivo fluorescence imaging, particularly for cancer diagnostics and image-guided interventions. Of the reported imaging agents, nanoparticles derived from conjugated polymers (CPNs) offer unique advantages to alternative materials including biocompatibility, remarkable absorption cross-sections, exceptional photostability, and tunable emission behavior independent of cell labeling functionalities. Herein, the current state of NIR-II emitting CPNs are summarized and structure-function-property relationships are highlighted that can be used to elevate the performance of next-generation CPNs. Methods for particle processing and incorporating cancer targeting modalities are discussed, as well as detailed characterization methods to improve interlaboratory comparisons of novel materials. Contemporary methods to specifically apply CPNs for cancer diagnostics and therapies are then highlighted. This review not only summarizes the current state of the field, but offers future directions and provides clarity to the advantages of CPNs over other classes of imaging agents.

Biomimetic-Membrane-Protected Plasmonic Nanostructures as Dual-Modality Contrast Agents for Correlated Surface-Enhanced Raman Scattering and Photoacoustic Detection of Hidden Tumor Lesions.

Optical imaging and spectroscopic modalities are of considerable current interest for in vivo cancer detection and image-guided surgery, but the turbid or scattering nature of biomedical tissues has severely limited their abilities to detect buried or occluded tumor lesions. Here we report the development of a dual-modality plasmonic nanostructure based on colloidal gold nanostars (AuNSs) for simultaneous surface-enhanced Raman scattering (SERS) and photoacoustic (PA) detection of tumor phantoms embedded (hidden) in ex vivo animal tissues. By using red blood cell membranes as a naturally derived biomimetic coating, we show that this class of dual-modality contrast agents can provide both Raman spectroscopic and PA signals for the detection and differentiation of hidden solid tumors with greatly improved depths of tissue penetration. Compared to previous polymer-coated AuNSs, the biomimetic coatings are also able to minimize protein adsorption and cellular uptake when exposed to human plasma without compromising their SERS or PA signals. We further show that tumor-targeting peptides (such as cyclic RGD) can be noncovalently inserted for targeting the ανß3-integrin receptors expressed on metastatic cancer cells and tracked via both SERS and PA imaging (PAI). Finally, we demonstrate image-guided resections of tumor-mimicking phantoms comprising metastatic tumor cells buried under layers of skin and fat tissues (6 mm in thickness). Specifically, PAI was used to determine the precise tumor location, while SERS spectroscopic signals were used for tumor identification and differentiation. This work opens the possibility of using these biomimetic dual-modality nanoparticles with superior signal and biological stability for intraoperative cancer detection and resection.