3 research outputs found
Iron-Loaded Magnetic Nanocapsules for pH-Triggered Drug Release and MRI Imaging
Magnetic
nanocapsules were synthesized for controlled drug release,
magnetically assisted delivery, and MRI imaging. These magnetic nanocapsules,
consisting of a stable iron nanocore and a mesoporous silica shell,
were synthesized by controlled encapsulation of ellipsoidal hematite
in silica, partial etching of the hematite core in acid, and reduction
of the core by hydrogen. The iron core provided a high saturation
magnetization and was stable against oxidation for at least 6 months
in air and 1 month in aqueous solution. The hollow space between the
iron core and mesoporous silica shell was used to load anticancer
drug and a T<sub>1</sub>-weighted MRI contrast agent (Gd-DTPA). These
multifunctional monodispersed magnetic “nanoeyes” were
coated by multiple polyelectrolyte layers of biocompatible poly-l-lysine and sodium alginate to control the drug release as
a function of pH. We studied pH-controlled release, magnetic hysteresis
curves, and T<sub>1</sub>/T<sub>2</sub> MRI contrast of the magnetic
nanoeyes. They also served as MRI contrast agents with relaxivities
of 8.6 mM<sup>–1</sup> s<sup>–1</sup> (<i>r</i><sub>1</sub>) and 285 mM<sup>–1</sup> s<sup>–1</sup> (<i>r</i><sub>2</sub>)
Monitoring pH-Triggered Drug Release from Radioluminescent Nanocapsules with X‑ray Excited Optical Luminescence
One of the greatest challenges in cancer therapy is to develop methods to deliver chemotherapy agents to tumor cells while reducing systemic toxicity to noncancerous cells. A promising approach to localizing drug release is to employ drug-loaded nanoparticles with coatings that release the drugs only in the presence of specific triggers found in the target cells such as pH, enzymes, or light. However, many parameters affect the nanoparticle distribution and drug release rate, and it is difficult to quantify drug release <i>in situ</i>. In this work, we show proof-of-principle for a “smart” radioluminescent nanocapsule with an X-ray excited optical luminescence (XEOL) spectrum that changes during release of the optically absorbing chemotherapy drug, doxorubicin. XEOL provides an almost background-free luminescent signal for measuring drug release from particles irradiated by a narrow X-ray beam. We study <i>in vitro</i> pH-triggered release rates of doxorubicin from nanocapsules coated with a pH-responsive polyelectrolyte multilayer using HPLC and XEOL spectroscopy. The doxorubicin was loaded to over 5% by weight and released from the capsule with a time constant <i>in vitro</i> of ∼36 days at pH 7.4 and 21 h at pH 5.0, respectively. The Gd<sub>2</sub>O<sub>2</sub>S:Eu nanocapsules are also paramagnetic at room temperature with similar magnetic susceptibility and similarly good MRI <i>T</i><sub>2</sub> relaxivities to Gd<sub>2</sub>O<sub>3</sub>, but the sulfur increases the radioluminescence intensity and shifts the spectrum. Empty nanocapsules did not affect cell viability up to concentrations of at least 250 μg/mL. These empty nanocapsules accumulated in a mouse liver and spleen following tail vein injection and could be observed <i>in vivo</i> using XEOL. The particles are synthesized with a versatile template synthesis technique which allows for control of particle size and shape. The XEOL analysis technique opens the door to noninvasive quantification of drug release as a function of nanoparticle size, shape, surface chemistry, and tissue type
Additional file 1 of Transcriptomic signatures of individual cell types in cerebral cavernous malformation
Additional file 1: Supplemental Methods, Supplemental Results, Figure S1, Figure S2 and Table S1