A Versatile Imaging and Therapeutic Platform Based on Dual-Band Luminescent Lanthanide Nanoparticles toward Tumor Metastasis Inhibition

Abstract

Upconversion (UC) luminescent lanthanide nanoparticles (LNPs) are expected to play an important role in imaging and photodynamic therapy (PDT) in vitro and in vivo. However, with the absorption of UC emissions by photosensitizers (PSs) to generate singlet oxygen ((1)O2) for PDT, the imaging signals from LNPs are significantly weakened. It is important to activate another imaging route to track the location of the LNPs during PDT process. In this work, Nd(3+)-sensitized LNPs with dual-band visible and near-infrared (NIR) emissions under single 808 nm excitation were reported to address this issue. The UC emissions in green could trigger covalently linked rose bengal (RB) molecules for efficient PDT, and NIR emissions deriving from Yb(3+) and magnetic resonance imaging (MRI) were used for imaging simultaneously. Notably, the designed therapeutic platform could further effectively avoid the overheating effect induced by the laser irradiation, due to the minimized absorption of biological media at around 808 nm. TdT-mediated dUTP nick end labeling (TUNEL) assay showed serious cell apoptosis in the tumor after PDT for 2 weeks, leading to an effective tumor inhibition rate of 67%. Benefit from the PDT, the tumor growth-induced liver and spleen burdens were largely attenuated, and the liver injury was also alleviated. More importantly, pulmonary and hepatic tumor metastases were significantly reduced after PDT. The Nd(3+)-sensitized LNPs provide a multifunctional nanoplatform for NIR light-assisted PDT with minimized heating effect and an effective inhibition of tumor growth and metastasis.

Advanced Functional Nanomaterials for Theranostics

“…For efficient replacement, the exchangeable ligands usually should coordinate with lanthanide ions. Surface ligands which have been reported for biological applications include poly(acrylic acid) (PAA), [202–204] hyaluronic acid (HA), [205] polyethylenimine (PEI), [206] polyethylene glycol (PEG), [207, 208] polyvinylpyrrolidone (PVP), [209] phospholipids, [195, 210, 211] and even photosensitizers [212, 213] . Other approaches include subjecting the hydrophobic outer shell (like oleic acid) to acid conditions with HCl aqueous solution, [214–216] , bioconjugating the surface, [217–219] using electronic-interactions between the UNCP core and hydrophilic molecule shells, [220] surface silanization, [221] amphiphilic polymer coating, [222, 223] and layer-by-layer assembly [224, 225] .…”

“…The longer excitation wavelengths of UCNP can eliminate interference from surrounding tissues, and emission light can further excite photosensitizers for photodynamic therapy. [231] Several photosensitizers have been combined with UCNPs for photodynamic therapy such as Rose Bengal (RB), [212, 213] Chlorin e6, [218, 232] a trans-platinum (IV) photosensitizer, [233, 234] and titanium dioxide [235–240] . In addition, by assembling UCNPs with gold-based materials, photothermal cancer therapy applications are possible [202, 228] .…”

808 nm-excited upconversion nanoprobes with low heating effect for targeted magnetic resonance imaging and high-efficacy photodynamic therapy in HER2-overexpressed breast cancer

“…Recently, considerable efforts have been devoted to developing novel upconversion nanoparticles excited by 808 nm laser. It was found that the Nd 3+ -sensitized upconversion nanoparticles exhibited efficient upconversion luminescence (UCL) under the excitation of 808 nm laser, in which Nd 3+ featured a sharp absorption band at 808 nm and acted as sensitizer [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. Moreover, the energy transfer from Nd 3+ to Yb 3+ to Er 3+ was expected to realize high-efficiency UCL with low heating effect and deep penetration under the excitation of 808 nm laser.…”

Cooperative and non-cooperative sensitization upconversion in lanthanide-doped LiYbF4 nanoparticles

“…[1][2][3][4][5][6][7][8][9] Yb 3+ , owing to its large absorption crosssection at ∼980 nm, is usually selected as a sensitizer in lanthanide (Ln 3+ )-doped UCNPs, which can effectively absorb near-infrared (NIR) photons and transfer the excitation energy to nearby activators to yield efficient upconversion (UC) luminescence. [10][11][12][13] …”