Persistent Luminescent Nanoparticles Containing Hydrogels for Targeted, Sustained, and Autofluorescence-Free Tumor Metastasis Imaging

Abstract

Metastasis is the primary cause of cancer morbidity and mortality. To obtain an effective diagnosis and treatment, precise imaging of tumor metastasis is required. Here we prepared persistent luminescent nanoparticles (PLNPs) containing a hydrogel (PL-gel) for targeted, sustained, and autofluorescence-free tumor metastasis imaging. PLNPs offered renewable long-lasting near-infrared (NIR) emitting without in situ radiation, favoring deep tissue penetration imaging without background interference. PLNPs were conjugated with 4-carboxyphenyl boronic acid (CPBA) to yield PLNPs-CPBA, which specifically recognized metastatic breast cancer cells (MBA-MD-231 cells) and enabled receptor-mediated endocytosis for specific cancer cell labeling. The PLNPs-CPBA-labeled cancer cells enabled sensitive imaging performance and high viability without influencing the migration and invasiveness of cancer cells for long-term tracking. PLNPs-CPBA were further encapsulated inside alginate to generate PL-gel for sustained PLNPs-CPBA release and tumor cell labeling, and the PL-gel showed enhanced renewable persistent luminescence compared to the PLNPs-CPBA suspension. The metastasis in the mouse breast cancer model was continuously tracked by persistent luminescence imaging, showing that PL-gel achieved noninvasive and highly selective imaging of tumor metastasis without background interference. Our PL-gel could be rationally designed to specifically target other types of cancer cells and thus provide a powerful and generic platform for the study of tumor metastasis.

Surface Modified Persistent Luminescence Probes for Biosensing and Bioimaging: A Review

“…prepared a NIR PLNPs probe for imaging of the metastasis process. [ 71 ] Zn 1.1 Ga 1.8 Ge 0.1 O 4 :Eu 0.009 , Cr 0.09 PLNPs were modified with 4‐carboxyphenyl boronic acid (CPBA) which allowed the receptor‐ mediated endocytosis for breast cancer cells labeling. After further being coated with alginate to generate persistent luminescence hydrogel (PL‐gel), PLNPs‐CPBA can be released sustainably and thus the increased renewable afterglow was realized.…”

Synthesis and Biomedical Applications of Lanthanides-Doped Persistent Luminescence Phosphors With NIR Emissions

“…In addition to inorganic materials, organic lanthanides co-doped system also shows the persistent luminescence phenomenon. Li et al synthesized an organic Er 3+ complex Er(F-TPIP) 3 [tetrakis(pentafluorophenyl)imidodiphosphinate] successfully (Li H.-F. et al, 2020). This complex had the NIR emission at around 1,500 nm due to the 4 I 13/2 -4 I 15/2 transition of Er 3+ .…”

“…As mentioned in the first part, PLPs are ideal materials for bioimaging since they can effectively avoid spontaneous fluorescence of biological tissues (Abdukayum et al, 2013;Li et al, 2020). However, the PLPs synthesized by traditional hightemperature reactions lack appropriate modifiable group on the surface (Du et al, 2017).…”

“…Lanthanidesdoped PLPs have good promise in tumor tracking and metastasis imaging due to their bright and rechargeable persistent luminescence. Zhao et al synthesized alginate containing PLPs Zn 1.1 Ga 1.8 G e0.1 O 4 :Eu 0.009 ,Cr 0.09 with the emission at around 698 nm, and they covalently modified the PLPs with 4carboxyphenylboric acid to target breast cancer cells (Zhao et al, 2020). The PLP probe was not interfered by spontaneous fluorescence and could achieve long-term tumor imaging.…”

pH‐Responsive Torpedo‐Like Persistent Luminescence Nanoparticles for Autofluorescence‐Free Biosensing and High‐Level Information Encryption

“…Recent advances in material synthesis via solvothermal route, [1i, 3] microwave‐assisted approach, [4] sol–gel process, [5] and template method [6] have continually improved the optical and physicochemical properties of PLNPs. In particular, hydrothermal method provides huge possibility for preparing monodisperse PLNPs [1g, 7] . Nonetheless, the preparation of uniform‐size and regular‐shape PLNPs with good afterglow features still remains a challenge.…”