RESUMO
The major challenge in current chemotherapy is to increase local effective therapeutic concentration of drugs as well as to minimize toxicity and side effects for patients. The targeted delivery of drugs to their desired site of action in a controlled manner plays an essential role in the development of drug formulations. A photocage refers to a caged molecule rendered biologically inert by a photolabile protecting group. Molecules are illuminated with light to liberate the caged group and then become active forms. In this study, we formulate upconversion nanoparticles (UCNPs) as the NIR-triggered targeting and drug delivery vehicles that successfully deliver in vitro and in vivo for near-infrared light photocontrolled targeting, bioimaging, and chemotherapy. It is noted that there has been no report on the systemic administration UCNP-based drug delivery agents for evaluation of bioimaging and chemotherapy. To achieve phototargeting, the tumor-homing agent (i.e., folic acid) has been constructed as a photoresponsive molecule. For the chemotherapeutic effect, the antitumor drug doxorubicin is thiolated on the surface of UCNPs, forming a disulfide bond that can be cleaved by lysosomal enzymes within the cells. The caged UNCPs can serve as a platform for the improvement of selective targeting and possible reduction of adverse side effects from chemotherapy.
Assuntos
Antineoplásicos/administração & dosagem , Raios Infravermelhos , Nanopartículas , Antineoplásicos/efeitos adversos , Sistemas de Liberação de Medicamentos , Células HeLa , Humanos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Espectrometria de Fluorescência , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
We synthesize a NIR MHI-148 dye, a lipophilic heptamethine cyanine, with capability in tumor-targeting property to accumulate in the mitochondria of tumor. In the context of MHI-148 dye, we demonstrate effective tumor targeting and NIR fluorescence in vitro and in vivo for MHI-148 as compared to ICG. A series of porous Gd silicates related nanoparticles, i.e. Gd silicate, Gd silicate@mSiO(2) (mSiO(2): mesoporous silica shell), and Gd(3+)-chelated Gd silicate@mSiO(2) (Gd(3+)-DOTA chelated on the mSiO(2)) are fabricated to demonstrate their magnetic resonance (MR) contrast imaging effects. Those Gd silicates related nanoparticles exhibit dual MR effect, expressing T(1)-brightened and T(2)-darkened effects, in lower magnetic field. In high magnetic field, an abnormal enhanced transverse relaxivity (r(2)) appears, showing an effective T(2)-lowering effect, possibly due to concentrated Gd amount and porous architecture. The r(2) value increases 4-5 times as the field strength increased from 3T to 7T. The Gd(3+)-chelated Gd silicate@mSiO(2) has given large r(2) (T(2)-lowering effect) up to 343.8 s(-1) mM(-1), which is even larger than the reported magnetic Fe(3)O(4) nanoparticles measured at the same field. Using a 9.4T animal micro MRI system we have seen effectively darken in signal for those porous Gd silicates related NPs, while no such phenomenon appears in commercial Gd-DOTA agent. The MHI-148 is then conjugated on the porous Gd silicate@mSiO(2) nanoparticles for a new paradigm with three functionalities for in vivo tumor targeting, near-infrared fluorescent and MR imaging by means of only using MHI-148 dye.