Protein triggered fluorescence switching of near-infrared emitting nanoparticles for contrast-enhanced imaging

Abstract

Sub-100 nm colloidal particles which are surface-functionalized with multiple environmentally-sensitive moieties have the potential to combine imaging, early detection, and the treatment of cancer with a single type of long-circulating "nanodevice". Deep tissue imaging is achievable through the development of particles which are surface-modified with fluorophores that operate in the nearinfrared (NIR) spectrum and where the fluorophore's signal can be maximized by "turning-on" the fluorescence only in the targeted tissue. We present a general approach for the synthesis of NIR emitting nanoparticles that exhibit a protein triggered activation/deactivation of the emission.Dispersing the particles into an aqueous solution, such as phosphate buffered saline (PBS), resulted in an aggregation of the hydrophobic fluorophores and a cessation of emission. The emission can be reinstated, or activated, by the conversion of the surface-attached fluorophores from an aggregate to a monomeric species with the addition of an albumin. This activated probe can be deactivated and returned to a quenched state by a simple tryptic digestion of the albumin. The methodology for emission switching offers a path to maximize the signal from the typically weak quantum yield inherent in NIR fluorophores.

A simple but efficient zwitterionization method towards cellulose membrane with superior antifouling property and biocompatibility

“…Then the mixture was stirred for 12 h at 298 K. The crude product was rinsed with acetone for three times followed by drying under vacuum at 303 K. The monomer was stored at 298 K before polymerization. 1 synthesized using a method similar to the literature [34]. A mixture of (N, N-dimethyl-3-aminopropyl)-trimethoxysilane (7.5 mL, 0.033 mol) and 1, 4-butanesultone (3.5 mL, 0.034 mol) was heated at 333 K for 2 h. The obtained precipitate was rinsed with acetone and dried under vacuum at 303 K. The product SBPT was stored at 298 K before polymerization.…”

Mini-review: fluorescence imaging in cancer cells using dye-doped nanoparticles

“…Co-localization studies were performed to establish that the uptake of the PA-azSQ particles was through endocytosis and in vitro fluorescence imaging was carried out in UMSCC22A (head and neck) and A549 (lung) cancer cells. 131 In 2011, Palma and colleagues, prepared BF 2 chelated tetraarylazadipyrromethene (near infrared dye) conjugated poly(styrene-co-methacrylic acid) particles. The dye was attached to the nanoparticles via a standard N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) coupling reaction.…”

“…These drawbacks are overcome easily when the fluorophore is covalently conjugated to the outside of the particle. 26,131 For the inner core, hydrophobic polymers such as poly(lactic-co-glycolic acid) (PLGA), poly(3-caprolactone) (PCL) and poly(methyl methacrylate) (PMMA) are preferred, as the hydrophobic matrix provides a strong affinity for the entrapment of poorly water solubilized fluorophores and drugs. 132,133 Typical nanoparticle size varies from 50 -500 nm, and the optimum nanoparticle size for tumor accumulation is between 70 and 200 nm as the nanoparticle uptake by the RES is in the size range between 150 and 300 nm.…”

“…134,135 In addition, it has been well established that a coating of PEG on the hydrophobic particle is necessary to render the nanoparticles biocompatible, avoid rapid clearance by the RES, and increase the circulation lifetime, which increases accumulation and allows distribution in different tissues. 26,131,[136][137][138] As mentioned previously poly(lactic acid) (PLA) based systems are the most popular choice for nanoparticles. PLA and its copolymers are one of the most extensively investigated matrix materials for nanoparticle-based diagnostic and drug delivery applications as they offer excellent biocompatibility, biodegradability into metabolizable moieties, and manufacturability.…”

Aminosquaraines as potential photodynamic agents: Synthesis and evaluation of in vitro cytotoxicity

“…Notwithstanding a considerable number of squaraine compounds has been designed and synthesized with the purpose of PDT sensitizers, the in vitro assessment of their photodynamic ability has been barely addressed [15][16][17][18][19][20][21][22][23][24]. The reports of in vivo evaluation are even scarcer [17,18,21,[25][26][27].…”