Ultrasmall Conjugated Polymer Nanoparticles with High Specificity for Targeted Cancer Cell Imaging

Abstract

Fluorescent and biocompatible organic nanoparticles have attracted great interest in cancer detection and imaging, but the nonspecific cellular uptake has limited the detection specificity and sensitivity. Herein, the authors report the ultrasmall conjugated polymer nanoparticles (CPNs) with bright far‐red/near‐infrared emission for targeted cancer imaging with high specificity. The sizes of the ultrasmall CPNs are around 6 nm (CPN6), while large CPNs show sizes around 30 nm (CPN30). Moreover, CPN6 exhibits largely improved fluorescence quantum yield (η) of 41% than CPN30 (25%). Benefiting from the ultrasmall size, bare CPN6 shows largely suppressed nonspecific cellular uptake as compared to CPN30, while cyclic arginine‐glycine‐aspartic acid (cRGD) functionalized CPN6 (cRGD‐CPN6) possesses excellent selectivity toward αvβ 3 integrin overexpressed MDA‐MB‐231 cells over other cells in cell mixtures. The faster body clearance of CPN6 over CPN30 indicates its greater potentials as a noninvasive nanoprobe for in vivo and practical applications.

Conjugated Polymer Nanoparticles toward In Vivo Theranostics – Focus on Targeting, Imaging, Therapy, and the Importance of Clearance

“…In the nanoprecipitation approach, we also start with a solution of conjugated polymer, which is injected into a nonsolvent for the conjugated polymer . By contrast, this nonsolvent is miscible with the solvent of the conjugated polymer, leading to fine precipitation of CPNs of diameters down to <10 nm . Here also, surfactants can be added to control the size of the CPNs and impart colloidal stability after nanoprecipitation.…”

“…Additionally, a maleimide carrying block copolymer stabilizer has been added during particle formation. The free maleimide groups can be used to attach anti‐HER2 affibodies or RGD peptides to the surface of the particles for tumor cell targeting . The particles fluoresce red (λ em = 612 nm) when excited in the green‐blue spectrum.…”

Ultrasmall Semiconducting Polymer Dots with Rapid Clearance for Second Near‐Infrared Photoacoustic Imaging and Photothermal Cancer Therapy

“…However, the S‐Pdots exhibit a quicker decrease than L‐Pdots because the clearance of L‐Pdots is largely through the biliary pathway while that of the S‐Pdots can be excreted through both the biliary pathway and urethral system. [ 34 ] In particular, the fluorescence intensity change of S‐Pdots and L‐Pdots in blood was also compared and displayed in Figure S11 (Supporting Information). The quick fluorescence intensity reduction of S‐Pdots in blood further validates its fast body clearance as compared to that of L‐Pdots.…”

“…[ 30–33 ] Therefore, the degradation and discharge of nanoparticles from living body is still an unresolved issue and now under further investigation. Very recently, Liu's group inspected ultrasmall conjugated polymer nanoparticles (6 nm in diameter) for targeted cancer cell imaging, [ 34 ] whereas Pu and co‐workers demonstrated that NIR‐II absorbing SPNs can be metabolizable with gradual clearance from living bodies after PAI. [ 35 ] However, it is still a great challenge to develop a phototheranostic nanoplatform for cancer therapy with excellent biocompatibility, efficient body clearance, visibility on clinical imaging, and high photothermal conversion efficiency.…”

Encapsulation-Dependent Enhanced Emission of Near-Infrared Nanoparticles Using in vivo Three-Photon Fluorescence Imaging

“…Thus, the depth of fluorescence imaging is usually limited, which is a bottleneck in practical biomedical applications. Among these imaging techniques, near infrared (NIR) fluorescence imaging (Shao et al, 2015;Li et al, 2016;Song et al, 2016;Feng et al, 2017) and multi-photon excited fluorescence microscopy have become two deep-tissue fluorescence imaging approaches because of their potential abilities to overcome tissue absorption and scattering. Three-photon fluorescence microscopy, which has the advantages of a high signal-to-noise ratio, high penetration depth and spatial resolution, shines in the field of biological imaging.…”