RBC Membrane Camouflaged Semiconducting Polymer Nanoparticles for Near-Infrared Photoacoustic Imaging and Photothermal Therapy

Abstract

Semiconducting conjugated polymer nanoparticles (SPNs) represent an emerging class of phototheranostic materials with great promise for cancer treatment. In this report, low-bandgap electron donor-acceptor (D-A)-conjugated SPNs with surface cloaked by red blood cell membrane (RBCM) are developed for highly effective photoacoustic imaging and photothermal therapy. The resulting RBCM-coated SPN (SPN@RBCM) displays remarkable near-infrared light absorption and good photostability, as well as high photothermal conversion efficiency for photoacoustic imaging and photothermal therapy. Particularly, due to the small size (< 5 nm), SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity. The RBCM endows the SPNs with prolonged systematic circulation time, less reticuloendothelial system uptake and reduced immune-recognition, hence improving tumor accumulation after intravenous injection, which provides strong photoacoustic signals and exerts excellent photothermal therapeutic effects. Thus, this work provides a valuable paradigm for safe and highly efficient tumor photoacoustic imaging and photothermal therapy for further clinical translation.

Keywords: Deep tumor penetration; Photoacoustic imaging; Photothermal therapy; Red blood cell membrane camouflage; Semiconducting conjugated polymer nanoparticles.

Scheme 1

Schematic illustration for the preparation of SPN@RBCM nanoparticles and their applications in photoacoustic imaging (PAI) and photothermal therapy (PTT)

Fig. 1

a Vis–NIR spectra of SP in THF, SPN and SPN@RBCM in PBS. b Vis–NIR spectra of SPN@RBCM in PBS at various concentrations ranged from 10 to 60 μg mL⁻¹. c Corresponding absorbance of SPN@RBCM at 808 nm in b. d TEM image of SPN, the inset picture is the enlarged image of a single nanoparticle, while the red dashed circle indicated its crystal structure. e DLS results of SPN and SPN@RBCM. f SDS-PAGE electrophoresis patterns of RBCM vesicles and SPN@RBCM

Fig. 2

a, b Temperature elevation of SCS@RBCM as a function of concentration for 1000 s, with a laser power density of 0.8 W cm⁻². c Photothermal performance of SCS@RBCM with laser irradiation for 1000 s (0.8 W cm⁻²) and then the laser was shut off. d Linear time data versus -ln θ obtained from the cooling period of Fig. 2d. e Photothermal stability of SCS@RBCM and ICG, upon four ‘‘On-to-Off’’ laser cycles. f Normalized absorbance of SCS@RBCM and ICG after irradiation with different times (0.8 W cm⁻²). g In vitro PA images of SCS@RBCM with different concentrations ranged from 10 to 60 µg mL⁻¹. h Linear dependence between the PA signals and concentrations of SPN@RBCM

Fig. 3

The in vitro therapeutic efficacy evaluated by CCK-8 assay (*p < 0.05, **p < 0.01, and ***p < 0.001; n = 4 per group) (a), live/dead assay (b), Scale bar: 200 μm, and Annexin V-FITC/PI apoptosis assay (c)

Fig. 4

a In vivo fluorescence imaging of 4T1 tumor-bearing mice as a function of time after intravenous injection of DiR-loaded SPN or SPN@RBCM. b Ex vivo fluorescence imaging of tumor and major organs harvested after 48 h of intravenous injection. c Normalized fluorescence intensity of SPN or SPN@RBCM in the serum at different time points after intravenous injection. d In vivo uptake of DiO-loaded SPN and SPN@RBCM by Macrophages which was analyzed by FACS. e In vivo PA imaging of 4T1 tumor-bearing mice as a function of time after intravenous injection of SPN or SPN@RBCM. f Schematic illustration of tumor tissue cut into three slices for fluorescence imaging. g Ex vivo fluorescence imaging of tumor slices. h Time-dependent ex vivo fluorescence imaging of major organs

Fig. 5

a IR thermal images of 4T1 tumor-bearing BALB/c mice under 808 nm laser irradiation (808 nm, 0.5 W cm⁻²) after PBS, SPN or SPN@RBCM injection. b–d Tumor growth curves (b), average tumor weight (c) and tumor photograph (d) after i.v. injection of PBS, SPN, and SPN@RBCM with or without 808 nm laser irradiation (*p < 0.05, **p < 0.01, and ***p < 0.001; n = 5 per group). e Optical microscopy images of tumor slices stained with H&E, antigen Ki67 and TUNEL after various treatments as indicated above. Scale bar: 100 μm. f, g Blood biochemistry (f) and routine indexes (g) of the BALB/c mice after i.v. injection of SPN@RBCM. h Histological H&E staining of major organs after various treatments as indicated above. Scale bar: 100 μm