A plasmonic fluorescent ratiometric temperature sensor for self-limiting hyperthermic applications utilizing FRET enhancement in the plasmonic field.

Nanoparticle mediated photo-induced hyperthermia holds much promise as a therapeutic solution for the management of diseases like cancer. The conventional methods of temperature measurements do not measure the actual temperature generated in the vicinity of the nanoparticles during illumination. In contrast, nano temperature sensors built on hyperthermic nanoparticles can relay local temperatures around the nanoparticles during thermal induction. In this study, we present a core shell construct consisting of a plasmonic core and a silica shell encapsulating a FRET pair of organic dyes for such application. The plasmonic core imparts photo-induced hyperthermic properties to the nanoconstruct, while the fluorescent shell enables ratiometric sensing of temperature. We see that even at a low dye encapsulation concentration, the shell displays a linear ratiometric fluorescence response to temperature and high energy transfer between the dye pair. Interestingly, Monte Carlo simulations, without considering the plasmonic core, show that the energy transfer in the system should be much smaller than that observed, confirming plasmon enhancement in the FRET energy transfer. We also show the ratiometric temperature measurement using these particles during photoinduced hyperthermia. This study suggests the use of plasmonic nanoparticles in the next generation "self-limiting" photothermal therapy.

Folate targeting self-limiting hyperthermic nanoparticles for controlled photothermal therapy.

Photothermal therapy utilizes photothermal agents and the use of nanoparticle agents is deemed advantageous for multiple reasons. Common nano-photothermal agents normally have high conversion efficiencies and heating rates, but bulk temperature measurement methods do not adequately represent the nanoscale temperatures of these nanoheaters. Herein, we report on the fabrication of self-limiting hyperthermic nanoparticles that can simultaneously photoinduce hyperthermia and report back temperature ratiometrically. The synthesized nanoparticles utilize a plasmonic core to achieve the photoinduced hyperthermic property and fluorescent FRET pairs entrapped in a silica shell to impart the ratiometric temperature sensing ability. The studies demonstrate the photoinduced hyperthermia with simultaneous temperature measurement using these particles and show that the particles can achieve a conversion efficiency of 19.5% despite the shell architecture. These folate-functionalized self-limiting photothermal agents are also used to demonstrate targeted photoinduced hyperthermia in a HeLa cell model.

Ultrabright fluorescent silica nanoparticles for in vivo targeting of xenografted human tumors and cancer cells in zebrafish.

New ultrabright fluorescent silica nanoparticles capable of the fast targeting of epithelial tumors in vivo are presented. The as-synthesized folate-functionalized ultrabright particles of 30-40 nm are 230 times brighter than quantum dots (QD450) and 50% brighter than the polymer dots with similar spectra (excitation 365 nm and emission 486 nm). To decrease non-specific targeting, particles are coated with polyethylene glycol (PEG). We demonstrate the in vivo targeting of xenographic human cervical epithelial tumors (HeLa cells) using zebrafish as a model system. The particles target tumors (and probably even individual HeLa cells) as small as 10-20 microns within 20-30 minutes after blood injection. To demonstrate the advantages of ultrabrightness, we repeated the experiments with similar but 200× less bright particles. Compared to those, ultrabright particles showed ∼3× faster tumor detection and ∼2× higher relative fluorescent contrast of tumors/cancer cells.

Ultrabright fluorescent cellulose acetate nanoparticles for imaging tumors through systemic and topical applications.

Cellulose acetate (CA), viscose, or artificial silk are biocompatible human-benign derivatives of cellulose, one of the most abundant biopolymers on earth. While various optical materials have been developed from CA, optical CA nanomaterials are nonexistent. Here we report on the assembly of a new family of extremely bright fluorescent CA nanoparticles (CA-dots), which are fully suitable for in vivo imaging / targeting applications. CA-dots can encapsulate a variety of molecular fluorophores. Using various commercially available fluorophores, we demonstrate that the fluorescence of CA-dots can be tuned within the entire UV-VIS-NIR spectrum. We also demonstrate excellent specific targeting of tumors in vivo, when injected in blood in zebrafish (xenograft model of human cervical epithelial cancer), and unusually strong ex-vivo topical labeling of colon cancer in mice utilizing CA folate-functionalized nanoparticles.

Data on ultrabright fluorescent cellulose acetate nanoparticles for imaging tumors through systemic and topical applications.

Characterization data of fluorescent nanoparticles made of cellulose acetate (CA-dots) are shown. The data in this article accompanies the research article "Ultrabright fluorescent cellulose acetate nanoparticles for imaging tumors through systemic and topical applications" [1]. The measurements and calculation of brightness of individual CA-dots are presented. The description of conjugation procedure Pluronic F127-Folic Acid copolymer and folic acid is shown. Identification of composition of CA dots using Raman and absorbance spectroscopy is demonstrated. The methods for image analysis of efficiency of CA-dot targeting of epithelial tumors xenografted in zebrafish is presented.

Ultrabright fluorescent mesoporous silica nanoparticles for prescreening of cervical cancer.

We report on the first functional use of recently introduced ultrabright fluorescent mesoporous silica nanoparticles, which are functionalized with folic acid, to distinguish cancerous and precancerous cervical epithelial cells from normal cells. The high brightness of the particles is advantageous for fast and reliable identification of both precancerous and cancerous cells. Normal and cancer cells were isolated from three healthy women and three cancer patients. Three precancerous cell lines were derived by immortalization of primary cultures of normal cells with human papillomavirus type-16 (HPV-16) DNA. We observed substantially different particle internalization by normal and cancerous/precancerous cells after a short incubation time of 15 minutes. Compared to HPV-DNA and cell pathology tests, which are currently used for prescreening of cervical cancer, we demonstrated that the specificity of our method was similar (94-95%), whereas its sensitivity was significantly better (95-97%) than the sensitivity of those currently used tests (30-80%). FROM THE CLINICAL EDITOR: This team of investigators reports on the development of a new screening test for cervical cancer using ultrabright fluorescent mesoporous silica nanoparticles functionalized with folic acid, enabling significantly better sensitivity (95-97% vs. 30-80%) and maintained specificity (94-95%) compared with current clinical tests. This test should find a way to clinical use in the near future.