Pioneering approaches for precise tumor removal involve fluorescence-guided surgery, while challenges persist, including the low fluorescence contrast observed at tumor boundaries and the potential for excessive damage to normal tissue at the edges. Lead/cadmium sulfide quantum dots (PbS@CdS QDs), boasting high quantum yields (QYs) and vivid fluorescence, have facilitated advancements in the second near-infrared window (NIR-II, 900–1700 nm). However, during fluorescent surgical navigation operations, hydrophilic coatings of these inorganic nanoparticles (NPs) guarantee biosafety; it also comes at the expense of losing a significant portion of QY and NIR-II fluorescence, causing heightened damage to normal tissues caused by cutting edges. Herein, we present hydrophilic core–shell PbS@CdS@PEG NPs with an exceptionally small diameter (∼8 nm) and a brilliant NIR-IIb (1500–1700 nm) emission at approximately 1600 nm. The mPEG-SH (MW: 2000) addresses the hydrophobicity and enhances the biosafety of PbS@CdS QDs. In vivo fluorescence-guided cervical tumor resection becomes achievable immediately upon injection of an aqueous solution of PbS@CdS@PEG NPs. Notably, this approach results in a significantly reduced thickness (100–500 μm) of damage to normal tissues at the margins of the resected tumors. With a high QY (∼30.2%) and robust resistance to photobleaching, NIR-IIb imaging is sustained throughout the imaging process.
Highly sensitive and specific discrimination of brain tumor margins from the surrounding parenchyma remains a formidable challenge. Limited by the short of photostable probes with deep tissue penetration and high efficiency of crossing the blood-brain-barrier (BBB), the development of fluorescence-guided surgery (FGS) of brain tumors was markedly constrained. Herein, we report the capability of the strong second near-infrared-IIb (NIR IIb, 1500−1700 nm) fluorescence from Er-based lanthanide nanoparticles in imaging-guided surgery of orthotopic glioma. We designed an energy-cascaded Er 3+ -Ce 3+ -A 3+ (A = Yb, Ho, Tm) system and prepared a series of NaErF 4 : [email protected] 4 @NaLuF 4 down-conversion nanoparticles (DCNPs) for optimizing the influence of NaAF 4 interlayer and Ce 3+ dopants. We modified the optimal NaErF 4 :2.5 % [email protected] 4 (0.9 nm)@NaLuF 4 DCNPs with Dye-brush polymer (Dye-BP) to facilitate 4 I 13/2 → 4 I 15/2 transition, which leads to an impressive 675-fold enhancement of 1525 nm fluorescence in aqueous solution under 808 nm excitation due to the excellent energy-cascaded downconversion (ECD), in comparison with that of NaErF 4 nanoparticles. We further modified these highly bright nanoparticles with tumor-targeting angiopep-2 peptide, and efficiently delivered them to the glioma by using the focused ultrasound sonication (FUS) to temporarily open the BBB. We obtained the highest tumor-to-background ratio (TBR = 12.5) ever reported in the targeted NIR IIb fluorescence imaging of small orthotopic glioma (size < 3 mm, depth> 3 mm) through intact skull and scalp, which was drastically improved to ∼150 after cardiac perfusion and craniotomy to ensure the precise resection of tumor. More importantly, the size of glioma measured from the width of fluorescence profile is very close to that from T 2 -weighted MRI images. Our work provides the insights into engineering NIR IIb fluorescence of lanthanide nanoparticles, and demonstrates the great potential of NIR IIb fluorescence imaging-guided surgery of tumor.
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