Emerging applications of upconverting nanoparticles in intestinal infection and colorectal cancer

Figures & data

Figure 1 In vivo applications of UCNPs in intestinal infection, inflammation, and colorectal cancer.

Notes: In this figure, we depict potential (red arrows) and current (blue arrow) target areas where UCNPs can be used either for imaging or treating infection, inflammation, and colon cancer. Bacterial infection and/or inflammation leading to IBD and colorectal cancer are depicted with black arrows. UCNPs loaded with antimicrobial and anti-inflammatory compounds can be used to treat infection, inflammation, and cancer. Furthermore, hypoxia-sensitive UCNPs can be used to monitor the hypoxic state of the gastrointestinal tract. Due to the NIR excitation range, UCNPs are currently being used for localized PDT in certain cancer forms.

Abbreviations: IBD, inflammatory bowel disease; NIR, near infrared; PDT, photodynamic therapy; UCNPs, upconverting nanoparticles.

Figure 2 UCNP characteristics.

Notes: (A) A cross-sectional schematic representation of a typical UCNP. This includes an optically inert host crystal where optically active Ln³⁺ activator and sensitizer ions are embedded by replacing the cations of host matrix in the crystallization process. (B) Lanthanide-based UCNPs in colloidal solution are able to convert NIR light into different wavelengths in the VIS region of the EM. Reproduced from Zhong Y, Tian G, Gu Z, et al. Elimination of Photon Quenching by a Transition Layer to Fabricate a Quenching-Shield Sandwich Structure for 800 nm Excited Upconversion Luminescence of Nd³⁺-Sensitized Nanoparticles. Adv Mater. 2013;26(18):2831–2837.²⁹ Publisher: John Wiley and Sons. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. (C) Ln³⁺ ions exhibit different emission spectral bands under NIR excitation, spanning from NIR to VIS and UV regions as each Ln³⁺ has its unique energy level structure.

Abbreviations: EM, electromagnetic; NIR, near infrared; UCNP, upconverting nanoparticle; UV, ultraviolet; VIS, visible.

Table 1 List of published studies where UCNPs were used to detect bacteria

Type of UCNPs’ system used	UCNPs’ conjugation	Bacteria/bacterial metabolite detected	Advantage	Reference
Multicolor UCNPs (NaYF4:Yb, Tm NaYF4:Yb, Ho NaYF4:Yb, Er/Mn)	Antibacteria aptamer	S. aureus, Vibrio parahemolyticus, and S. typhimurium	High specificity, simultaneous detection	Wu et al^Citation69
NaYF4:Yb, Er	Anti-E. coli antibody	E. coli	High photostability	Ong et al^Citation70
NaYF4:Yb, Er	Anti-E. coli antibody	E. coli	Low detection limit – 10 CFU/mL	Pan et al^Citation71
NaYF4:Yb0.2, Tm 0.02	Anti-ochratoxin A aptamer	Ochratoxin A	High sensitivity	Dai et al ^Citation72
NaYF4:Tm@SiO2, NaYF4:Er@SiO2	Anti-P. gingivalis antibody	P. gingivalis	Low detection limit – 10 CFU/mL	Qin et al^Citation73
LET, Mn^2+-doped NaYF4:Yb, Tm as donor and Au nanorod as acceptor	Anti-Salmonella aptamer	S. typhimurium	Low detection limit – 11 CFU/mL	Cheng et al^Citation74
FRET, Au NP as donor and NaYF4:Yb/Er as acceptor	Antiaptamer cDNA	E. coli, B. subtilis, and S. aureus	Detect E. coli in real food and water samples	Jin et al^Citation75
Optical trapping, KLu2F7:Yb^3+, Er^3+	None	E. coli	Single bacteria detection	Xin et al^Citation76
Bio-microlens to enhance the upconversion fluorescence of NaYF4:Yb^3+/Tm^3+	None	E. coli	Single bacteria detection	Li et al^Citation77

Abbreviations: B. subtilis, Bacillus subtilis; E. coli, Escherichia coli; FRET, fluorescence resonance energy transfer; LET, luminescence energy transfer; NP, nanoparticle; P. gingivalis, Porphyromonas gingivalis; S. aureus, Staphylococcus aureus; S. typhimurium, Salmonella typhimurium; UCNPs, upconverting nanoparticles.

Figure 3 Mode of action of UCNPs in visualizing and killing bacteria.

Notes: In this figure, we summarize published work on UCNPs’ role in visualizing and killing bacteria. (A) Functionalized UCNPs targeting bacteria with NIR/VIS emission range is used to image the bacteria. (B) UCNPs loaded with antimicrobial compounds or with an UV emission range are used for localized antimicrobial activity.

Abbreviations: NIR, near infrared; UCNPs, upconverting nanoparticles; UV, ultraviolet; VIS, visible.

Table 2 Antimicrobial actions of UCNPs

Type of UCNPs’ system used	Antimicrobial	Target bacterium	Reference
β-NaYF4:Tm^3+ coated with TiO2	d-amino acid (d-tyrosine) and ROS	Individual B. subtilis and biofilm	Wei et al^Citation78
β-NaYF4:Yb, Tm	PFVCN	E. coli	Li et al^Citation79
Oleic acid capped β-NaYF4:23%Yb, 2%Er@NaYF4 zinc phthalocyanine as photosensitizer	OC and ROS inducing zinc phthalocyanine	Multidrug-resistant S. aureus and β-lactamase-producing E. coli	Li et al^Citation80

Abbreviations: B. subtilis, Bacillus subtilis; E. coli, Escherichia coli; OC, N-octyl chitosan; PFVCN, poly(9,9-bis[6,6-{N,N,N-trimethylaminium}-fluorene]-2,7-ylenevinylene)-co-alt-2,5-dicyano-1,4-phenylene]; S. aureus, Staphylococcus aureus; UCNPs, upconverting nanoparticles.

Table 3 Colorectal cancer detection and treatment using UCNPs

Type of UCNPs	UCNPs’ conjugation	Ligand specificity	Tumor model	Route of UCNPs’ administration	Type of tumor detected	Anticancer property used	Reference
NaGdF4:Yb, Er@NaGdF4 coated with PEG	FA	Folate-receptor overexpressing melanoma cells	Chemically induced primary colorectal cancer model	Intravenous injection	Primary colorectal cancer	None	Liu et al^Citation84
NaLuF4:Yb, Tm@NaLuF4 nanocrystals modified with citrates	None	Passive targeting	Kunming mice injected with human colorectal cancer LOVO cell line	Intraperitoneal and intravenous injected	Colorectal tumor	None	Gao et al^Citation85
PEGylated NaYF4 (Y/Yb/Er=78:20:2)	Ce6, a photosensitizer, and imiquimod (R837), a toll-like-receptor-7 agonist and an anti-CTLA-4, checkpoint inhibitor	None	BALB/c mice, subcutaneously injected CT26 cells	Intratumor injection	Colorectal tumor	PDT with checkpoint inhibitor	Xu et al^Citation86

Abbreviations: Ce6, Chlorin e6; FA, folic acid; PDT, photodynamic therapy; PEG, polyethylene glycol.

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