Controlled Synthesis of Up-Conversion NaYF4:Yb,Tm Nanoparticles for Drug Release under Near IR-Light Therapy

Abstract

Up-Conversion materials have received great attention in drug delivery applications in recent years. A specifically emerging field includes the development of strategies focusing on photon processes that promote the development of novel platforms for the efficient transport and the controlled release of drug molecules in the harsh microenvironment. Here, modified reaction time, thermal treatment, and pH conditions were controlled in the synthesis of NaYF₄:Yb,Tm up-converted (UC) material to improve its photoluminescence properties. The best blue-emission performance was achieved for the UC3 sample prepared through 24 h-synthesis without thermal treatment at a pH of 5, which promotes the presence of the β-phase and smaller particle size. NaYF₄:Yb,Tm has resulted in a highly efficient blue emitter material for light-driven drug release under near-IR wavelength. Thus, NaYF₄:Yb,Tm up-converted material promotes the N-O bond cleavage of the oxime ester of Ciprofloxacin (prodrug) as a highly efficient photosensitized drug delivery process. HPLC chromatography and transient absorption spectroscopy measurements were performed to evaluate the drug release conversion rate. UC3 has resulted in a very stable and easily recovered material that can be used in several reaction cycles. This straightforward methodology can be extended to other drugs containing photoactive chromophores and is present as an alternative for drug release systems.

Keywords: Near IR-Light Therapy; Up-Conversion; drug-delivery.

Scheme 1

Representation of the methodology for photosensitized drug delivery based on cleaving the N-O covalent bond by means NaYF₄:Yb,Tm UC nanoparticles.

Figure 1

(A) Photoluminescence. Energy transitions sachem for NaYF₄:Yb,Tm materials (Inset) and (B) X-ray diffraction, and (C) SEM photographs of UC1, UC2, and UC3 samples.

Figure 2

(A) Photoluminescence, (B) X-ray diffraction XRD patterns match closely with that of hexagonal β-NaYF₄ phase (JCPDF 28–1192), and (C) SEM photographs of UC3-UC7 samples under different pH synthesis conditions.

Figure 3

(A) Normalized absorption spectra of ciprofloxacin derivatives (CF or CF-OE, 20 μM) in CH₂Cl₂ (black and red traces for CF or CF-OE, respectively) and in acidic media (purple shadow for CF-OE). The normalized photoluminescence spectrum of UC3 in solid (blue trace) is included for comparison. (B) Steady-state fluorescence for CF (red), CF-OE (black), and CF-OE un acidic media (blue) in dichloromethane. Inset: normalized decay traces.

Figure 4

(A) Conversion rate of CF (red) or CF-OE (blue) using UC3 upon increasing irradiation times (λ_exc = 980 nm), at 0.5 M of CF-OE in deaerated CH₂Cl₂ (10% FA v/v); (B) Reusability of UC3 by monitoring the conversion rate of the formation of CF upon increasing irradiation times (λ_exc = 980 nm) during five consecutive cycles. The graph shows the maximum percentage of CF formation after 90 min under irradiation.

Figure 5

(A) Transient absorption spectra (TAS, λ_exc = 980 nm) for UC3 in deaerated dichloromethane suspension solution immediately (blue trace) and after 10 ns (cyan trace) after the laser pulse. (B) Transient absorption spectra (λ_exc = 355 nm) for the mixture reaction in deaerated methylene chloride (10% FA v/v) upon irradiation times. The orange trace corresponds to the commercial BP reference.