In Vivo Real-Time Pharmaceutical Evaluations of Near-Infrared II Fluorescent Nanomedicine Bound Polyethylene Glycol Ligands for Tumor Photothermal Ablation

Abstract

Pharmaceutical evaluations of nanomedicines are of great significance for their further launch into industry and clinic. Near-infrared (NIR) fluorescence imaging plays essential roles in preclinical drug development by providing important insights into the biodistributions of drugs in vivo with deep tissue penetration and high spatiotemporal resolution. However, NIR-II fluorescence imaging has rarely been exploited for in vivo real-time pharmaceutical evaluations of nanomedicine. Herein, we developed a highly emissive NIR-II luminophore to establish a versatile nanoplatform to noninvasively monitor the in vivo metabolism of nanomedicines bound various polyethylene glycol (PEG) ligands in a real-time manner. An alternative D–A–D conjugated oligomer (DTTB) was synthesized to achieve NIR-II emission peaked at ∼1050 nm with high fluorescence QYs of 13.4% and a large absorption coefficient. By anchoring with the DTTB molecule, intrinsically fluorescent micelles were fabricated and bound with PEG ligands at various chain lengths. In vivo NIR-II fluorescence and photoacoustic imaging results revealed that an appropriate PEG chain length could effectively contribute to the longer blood circulation and better tumor targeting. In vivo therapeutic experiments also confirmed the optimized nanomedicines have efficient photothermal elimination of tumors and good biosafety. This work offered an alternative highly fluorescent NIR-II material and demonstrated a promising approach for real-time pharmaceutical evaluation of nanomedicine in vivo.

NIR‐II Organic Nanotheranostics for Precision Oncotherapy

“…FLI image: Reproduced with permission. [59] Copyright 2020, American Chemical Society. PTT image: Reproduced with permission.…”

“…Li et al designed a new thiadiazolobenzotriazole (BTZ) acceptor as a NIR-II core to develop a NIR-II SM DTTB, which showed a high fluorescence QY of 13.4% (IR1061 as the reference with QY of 0.75% in DCM) and a large absorption coefficient of 4.9 × 10 4 L mol −1 cm −1 at 808 nm. [59] Three amphiphilic polymers with different lengths of PEG chains were used to encapsulate DTTB to form the nanomicelles of DTTB@PEG-1K, DTTB@PEG-3K, and DTTB@PEG-5K with different surface morphology. The three nanomicelles with similar size distribution exhibited an absorption and emission peak at 750 and 1050 nm, respectively.…”

Conjugated Polymers: Optical Toolbox for Bioimaging and Cancer Therapy

“…Apart from fluorescence emission in the visible region, CPs can extend their emission spectra into NIR region through D-A design, and thus were used in NIR imaging to improve the penetration depth and sensitivity of bioimaging in biological tissue and living animals. [39,52,53] Liu et al first reported a far-red/ NIR fluorescent CP PFBTDBT which consisted of fluorene and benzothiadiazole. After further fabrications, the PFBTDBT was prepared into a NIR nanoparticle with an emission maximum at 698nm, which offered an attractive fluorescence material for in vivo imaging.…”

Activatable NIR‐II Fluorescent Probes Applied in Biomedicine: Progress and Perspectives

“…Benefitting from continuous improvement in the research of NIR‐II AFPs, the probes can effectively actualize superior tissue visualization, accurate disease diagnosis and available therapy. In recent years, more and more NIR‐II‐based therapeutic applications such as drug delivery and release, [107–111] imaging‐guided surgery [112–115] and imaging‐guided photothermal therapy (PTT) [116–119] have made remarkable progress and demonstrated their superior advantages in diseases therapy.…”

“…Furthermore, Liang's group reported a NIR‐II fluorescent probe that was successfully applied in visualization for metabolic behaviors and real‐time drug assessment of nanomedicine in vivo [111] . The acquired NIR‐II probe was a D‐A‐D conjugated oligomer, which was constructed by using thiadiazolobenzotriazole (BTZ) as the NIR‐II acceptor core and then anchoring the oligomer into polyethylene glycolated micelles.…”