Recent progress in the development of upconversion nanomaterials in bioimaging and disease treatment

Abstract

Multifunctional lanthanide-based upconversion nanoparticles (UCNPs), which feature efficiently convert low-energy photons into high-energy photons, have attracted considerable attention in the domain of materials science and biomedical applications. Due to their unique photophysical properties, including light-emitting stability, excellent upconversion luminescence efficiency, low autofluorescence, and high detection sensitivity, and high penetration depth in samples, UCNPs have been widely applied in biomedical applications, such as biosensing, imaging and theranostics. In this review, we briefly introduced the major components of UCNPs and the luminescence mechanism. Then, we compared several common design synthesis strategies and presented their advantages and disadvantages. Several examples of the functionalization of UCNPs were given. Next, we detailed their biological applications in bioimaging and disease treatment, particularly drug delivery and photodynamic therapy, including antibacterial photodynamic therapy. Finally, the future practical applications in materials science and biomedical fields, as well as the remaining challenges to UCNPs application, were described. This review provides useful practical information and insights for the research on and application of UCNPs in the field of cancer.

Keywords: Bioimaging; Biomedical applications; Drug delivery; PDT; Upconversion; aPDT.

Fig. 1

a The basic composition of UCNPs and b schematic illustration of the mechanism of organic dye-sensitized UCNPs

Fig. 2

Upconversion energy transfer mechanism based on Yb³⁺ and Er³⁺, and on Yb³⁺ and Tm³⁺ under 980 nm excitation

Fig. 3

Main upconversion processes of doped UCNP

Fig. 4

Diagram of the liquid–solid-solution phase transfer hydrothermal synthesis mechanism

Fig. 5

a Schematic illustration of the hydrothermal preparation synthetic procedure of UCNPs@TiO₂ NCs [79]. b TEM images of the original NaYF₄:Yb³⁺,Tm³⁺ cores (scale bar = 50 nm). c Sol–gel method for synthesized 2-aminoethyl dihydrogen phosphate-stabilized NaYF₄:Yb³⁺,Er³⁺ nanoparticles (scale bar: 100 nm) [97]. d UPP@ovalbumin were prepared by microemulsion synthesis [98]. (Copyright 2015, 2012 and 2015. American Chemical Society. Reproduced with permission.)

Fig. 6

Commonly used methods of functionalizing UCNPs

Fig. 7

a Hydrophilic modification structural illustration of a multicolor core/shell UCNP, b–e TEM images of the UCNP before the growth of NaYF₄:Yb³⁺/Er³⁺ shell core and after functionalization of NaYF₄:Yb³⁺/Er³⁺ with zinc-dipicolylamine analog (TDPA-Zn²⁺) and MSNs [114]. ( Copyright 2015. American Chemical Society. Reproduced with permission.)

Fig. 8

Surface engineering of a UCLNP towards protein-reactive, multicolor upconverting labels

Fig. 9

Schematic diagram of the chemical coupling method to combine Fe₃O₄ with NaYF₄ nanomaterials for biomarker HeLa cells [120]. ( Copyright 2010. The National Center for Biotechnology Information. Reproduced with permission.)

Fig. 10

Schematic illustration of the design principle of DNA nanosensors based on upconversion fluorescent resonance energy transfer

Fig. 11

Schematic illustration of antigen-loaded UCNPs for dendritic cell (DC) stimulation, tracking and vaccination in DC-based immunotherapy [98]. ( Copyright 2015. American Chemical Society. Reproduced with permission.)

Fig. 12

Time-dependent in vivo upconversion luminescence imaging of subcutaneous U87MG tumor (left hind leg, indicated by short arrows) and MCF-7 tumor (right hind leg, indicated by long arrows) borne by athymic nude mice after intravenous injection of UCNP-RGD over a 24 h period [146]. ( Copyright 2009. American Chemical Society. Reproduced with permission.)

Fig. 13

In vivo lymphatic imaging using PoP-UCNPs in mice. a Traditional FL and b UC images c full anatomy PET, d merged PET/CT and e CL images and PA images f  [153]. (Copyright 2015. Advanced Materials. Reproduced with permission)

Fig. 14

UCNP and DOX were loaded into gel nanoparticles and modified with PEI and DMMA to construct a nanolongan schematic with multiple transformations and corresponding anticancer mechanisms. ( Copyright 2019. American Chemical Society. Reproduced with permission.)

Fig. 15

Synthesis route of photo-induced charge-variable cationic conjugated polyelectrolyte brush and its photolytic process. ( Copyright 2017. John Wiley and Sons. Reproduced with permission.)

Fig. 16

a Schematic illustration of the design of UCNP based drug delivery system for photodynamic therapy. b Plot for the potential molecular mechanism of inducing apoptosis with UCNPs@TiO₂-based NIR light-mediated PDT treatment [176]. c Scheme summarizing the mechanisms of combining NIR-mediated PDT with CTLA-4 checkpoint blockade for cancer immunotherapy. UCNP-Ce6-R837 nanoparticles under NIR light would enable effective photodynamic destruction of tumors [116]. ( Copyright 2015, 2017. American Chemical Society. Reproduced with permission.)

Fig. 17

Synthesis of NaYF₄:Yb³⁺,Tm³⁺@TiO₂ and mechanism of aPDT under NIR irradiation. Upon NIR irradiation, the UCNP nucleus converts NIR light into ultraviolet (UV) light and the UV light in turn excites TiO₂ to generate active oxygen, which eventually causes oxidative damage against the microorganisms. ( Copyright 2019. Elsevier. Reproduced with permission.)