Small upconverting fluorescent nanoparticles for biomedical applications.

Fluorescent labels have been widely used for biological applications, primarily in imaging and assays. Traditional fluorophores such as fluorescent dyes are mainly based on downconversion fluorescence, which have several drawbacks such as photobleaching, high background noise from autofluorescence, and considerable photodamage to biological materials. Upconverting fluorescent nanoparticles emit detectable photons of higher energy in the near-infrared (NIR) or visible range upon irradiation with an NIR light in a process termed 'upconversion.' They overcome some of the disadvantages faced by conventional downconversion labels, thus making them an ideal fluorescent label for biological applications. This review looks at the development of these particles, critically examines the reported applications, and discusses their future in biomedicine.

Upconverting nanoparticles as nanotransducers for photodynamic therapy in cancer cells.

BACKGROUND: Photodynamic therapy (PDT) involves killing of diseased cells by excitation of photosensitizer chemicals with high-energy light to produce cytotoxic oxygen species from surrounding dissolved oxygen. However, poor tissue penetration of high-energy light and hydrophobic photosensitizers limits the effectiveness to superficial pathologies. Upconversion phosphor nanoparticles convert low-energy radiation to higher-energy emissions. AIM: To create upconverting 'nanotransducers' to enable PDT in deep tissues. RESULTS: Monodisperse, 50 nm PEI/NaYF(4):Yb(3+),Er(3+) nanoparticles producing green/red emission on near-infrared (NIR) excitation were targeted to folate receptors on human colon cancer cells and imaged with high signal-to-background ratio. It was demonstrated that these particles could be excited after deep intramuscular injection in rats. On NIR excitation, the particles, modified with zinc phthalocyanin photosensitizer, released singlet oxygen and, after targeted binding to cancer cells, resulted in significant cell destruction. CONCLUSION: Potential clinical use of these nanoparticles includes imaging and PDT of cancer in deep tissues.

Upconversion fluorescence imaging of cells and small animals using lanthanide doped nanocrystals.

Upconversion fluorescence imaging technique with excitation in the near-infrared (NIR) region has been used for imaging of biological cells and tissues. This has several advantages, including absence of photo-damage to living organisms, very low auto-fluorescence, high detection sensitivity, and high light penetration depth in biological tissues. In this report we demonstrate the use of a new upconversion fluorophore, lanthanide doped nanocrystals, for imaging of cells and some deep tissues in animal. Polyethyleneimine (PEI) coated NaYF(4):Yb,Er nanoparticles were synthesized, which produce very strong upconversion fluorescence when excited at 980 nm by a NIR laser. The nanoparticles were shown to be stable in physiologic buffered saline (PBS), non-toxic to bone marrow stem cells, and resistant to photo-bleaching. The nanoparticles delivered into some cell lines or injected intradermally and intramuscularly into some tissues either near the body surface or deep in the body of rats showed visible fluorescence, when exposed to a 980 nm NIR laser. To the best of our knowledge, this represents the first demonstration of use of upconversion fluorophores for cellular and tissue imaging.