RESUMEN
Cancer remains the second leading cause of death after heart disease in the US. While metastasized cancers such as breast, prostate, and colon are incurable, before their distant spread, these diseases have invaded the lymphatic system as a first step in their progression. Hence, proper evaluation of the disease state of the lymphatics which drain a tumor site is crucial to staging and the formation of a treatment plan. Current lymphatic imaging modalities with visible dyes and radionucleotide tracers offer limited sensitivity and poor resolution; however, newer tools using nanocarriers, quantum dots, and magnetic resonance imaging promise to vastly improve the staging of lymphatic spread without needless biopsies. Concurrent with the improvement of lymphatic imaging agents, has been the development of drug carriers that can localize chemotherapy to the lymphatic system, thus improving the treatment of localized disease while minimizing the exposure of healthy organs to cytotoxic drugs. This review will focus on the use of various nanoparticulate and polymeric systems that have been developed for imaging and drug delivery to the lymph system, how these new devices improve upon current technologies, and where further improvement is needed.
Asunto(s)
Sistemas de Liberación de Medicamentos , Sistema Linfático/metabolismo , Neoplasias/patología , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Diagnóstico por Imagen/métodos , Portadores de Fármacos/química , Humanos , Metástasis Linfática , Nanopartículas , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Polímeros/químicaRESUMEN
BACKGROUND: Synthetic nanoparticles are emerging as versatile tools in biomedical applications, particularly in the area of biomedical imaging. Nanoparticles 1 - 100 nm in diameter have dimensions comparable to biological functional units. Diverse surface chemistries, unique magnetic properties, tunable absorption and emission properties, and recent advances in the synthesis and engineering of various nanoparticles suggest their potential as probes for early detection of diseases such as cancer. Surface functionalization has expanded further the potential of nanoparticles as probes for molecular imaging. OBJECTIVE: To summarize emerging research of nanoparticles for biomedical imaging with increased selectivity and reduced nonspecific uptake with increased spatial resolution containing stabilizers conjugated with targeting ligands. METHODS: This review summarizes recent technological advances in the synthesis of various nanoparticle probes, and surveys methods to improve the targeting of nanoparticles for their application in biomedical imaging. CONCLUSION: Structural design of nanomaterials for biomedical imaging continues to expand and diversify. Synthetic methods have aimed to control the size and surface characteristics of nanoparticles to control distribution, half-life and elimination. Although molecular imaging applications using nanoparticles are advancing into clinical applications, challenges such as storage stability and long-term toxicology should continue to be addressed.
Asunto(s)
Imagen Molecular/métodos , Nanopartículas , Animales , Humanos , Nanopartículas/efectos adversos , Nanopartículas/química , Nanopartículas/uso terapéutico , Nanotecnología/métodos , Especificidad de Órganos , Propiedades de SuperficieRESUMEN
In order to understand how electronic and other structural characteristics of biphenyl phosphine ligands affect Pd-catalyzed C-N and C-C bond-forming reactions, a new ligand, 2-(dicyclohexylphosphino)-4'-(N,N-dimethylamino)-1,1'-biphenyl, was synthesized. This compound is isomeric with the commercially available 2-(dicyclohexylphosphino)-2'-(N,N-dimethylamino)-1,1'-biphenyl that has been useful in C-N bond-forming reactions of nucleosides. The new p-dimethylamino biphenyl ligand bears electronic similarities to the o-dimethylamino isomer, but it also possesses structural similarities to 2-(dicyclohexylphosphino)biphenyl, such as the unsubstituted ortho positions in the non-phosphine ring. Whereas 2-(dicyclohexylphosphino)biphenyl can support catalysts for C-C bond formation, it was not effective in promoting aryl amination of a nucleoside substrate. However, the new ligand proved to be effective in promoting both aryl amination and C-C bond-forming reactions of nucleoside substrates, with some reactions even occurring at room temperature. Thus, the composite structural elements of this new ligand are thought to be criteria for reactivity of the catalytic system derived from it. We have probed the structures of the isomeric N,N-dimethylamino biphenyl ligands by X-ray crystallographic analysis. Interactions of the two ligands with Pd(OAc)(2) have been investigated by (31)P NMR, and they show substantial stoichiometry-dependent differences. These results have been compared to the interactions of Pd(OAc)(2) with 2-(dicyclohexylphosphino)biphenyl as well as 2-(di-tert-butylphosphino)biphenyl, and they reveal marked differences as well. In this process, three cyclopalladated biaryl derivatives have been isolated and characterized by X-ray analysis.
Asunto(s)
Compuestos de Bifenilo/química , Carbono/química , Nitrógeno/química , Fosfinas/química , Compuestos de Bifenilo/síntesis química , Catálisis , Cristalografía por Rayos X , Electrones , Ligandos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Conformación Molecular , Nucleósidos/química , Compuestos Organometálicos/química , Paladio/química , Relación Estructura-ActividadRESUMEN
[reaction: see text] Palladium catalyzed cross coupling of nucleoside arylsulfonates and arylboronic acids has been accomplished under mild conditions and at room temperature. Among three structurally similar ligands that differ in their steric and electronic properties, one yielded an effective catalyst in conjunction with Pd(OAc)2. Of the nucleoside arylsulfonates evaluated, the O6-(2,4,6-trimethylphenyl)sulfonate proved optimal, but other alkyl and alkoxy derivatives were also reasonably reactive. On the other hand, a 2-nitrophenyl and a 2-thienyl derivative were ineffective substrates. PhMe and THP were suitable as solvents, yielding good results in several cases, although reactions of some arylboronic acids were faster in PhMe. In contrast, reactions of arylboronic acids bearing strongly electron-withdrawing groups proceeded more successfully in THP. Interplay between several factors that include substituents on the nucleoside arylsulfonate, ligand substituents, and solvent is responsible for successful cross coupling. Using 31P NMR, an initial investigation has been conducted to study the interaction of Pd(OAc)2 with the ligand. At a 1:1 stoichiometry of ligand and Pd(OAc)2, a predominant species, likely a cyclopalladation product, was obtained. At a 2:1 ratio of ligand and Pd(OAc)2, a different species bearing chemically distinct phosphine ligands was observed. Both complexes display catalytic activity, although the 2:1 species may be superior.
Asunto(s)
Arilsulfonatos/síntesis química , Nucleósidos/síntesis química , Temperatura , Catálisis , Paladio , SolventesAsunto(s)
Arilsulfonatos/química , Nucleósidos/química , Paladio/química , Purinas/química , Aminación , Catálisis , Ligandos , Estructura MolecularRESUMEN
Pd-catalyzed coupling of the axially constrained, less reactive benzo[a]pyrene bay-region amino benzoates, derived from the tetrahydro and diol epoxides, with C-6 and C-2 halopurine deoxynucleosides offers an efficient approach to the synthesis of the corresponding nucleoside-epoxide adducts. Also reported are the first examples involving the coupling of a 6-chloropurine deoxynucleoside with these amines, a reaction that is difficult by direct halide displacement. Certain mechanistic aspects of this metal-catalyzed C-N bond formation are also discussed. [reaction--see text]