The invention relates to a multifunctional system stable in a physiological medium, which includes in the same platform an anti-carcinogenic molecule, an imaging agent and a directing molecule that interacts specifically with cancer-cell membrane receptors, the system allowing pathological tissue imaging and pharmacological action to be carried out jointly with high specificity. The intratumoral administration of the system facilitates selective diffusion to cancer cells and minimises the disadvantages of chemotherapy.

An aqueous synthesis methodology for the preparation of silica nanoparticles (SNPs), core-shell SNPs having, for example, a size of 2 to 15 nm and narrow size-dispersion with size control below 1 nm, i.e. at the level of a single atomic layer. Different types of dyes, including near infrared (NIR) emitters, can be covalently encapsulated within and brightness can be enhanced via addition of extra silica shells. The surface may be functionalized with polyethylene glycol (PEG) groups and, optionally, specific surface ligands. This aqueous synthesis methodology also enables synthesis of 2 to 15 nm sized fluorescent core and core-shell aluminosilicate nanoparticles (ASNPs) which may also be surface functionalized. Encapsulation efficiency and brightness of highly negatively charged NIR fluorophores is enhanced relative to the corresponding SNPs without aluminum.

Described is a versatile surface modification approach to, for example, modularly and orthogonally functionalize nanoparticles (NPs) such as, for example, PEGylated nanoparticles, ith various types of different functional ligands (functional groups) on the NP surface. It enables the synthesis of, for example, penta-functional PEGylated nanoparticles integrating a variety of properties into a single NP, e.g., fluorescence detection, specific cell targeting, radioisotope chelating/labeling, ratiometric pH sensing, and drug delivery, while the overall NP size remains, for example, below 10 nm.

Embodiments disclosed herein relate to internal combustion engines, combustion systems that include such internal combustion engines, and controls for controlling operation of the combustion engine. The internal combustion engine may include one or more mechanisms for injecting fuel, air, fuel-air mixture, or combinations thereof directly into one or more cylinders, and controls may operate or direct operation of such mechanisms.

A self-assembled nanostructure including an amphiphilic chitosan and a contrast agent compound is provided. The contrast agent compound is grafted to the amphiphilic chitosan. The chemical bonding between the amphiphilic chitosan and the contrast agent compound has a synergistic effect to further improve the contrasting ability of the contrast agent compound.

[Problem] To provide a novel fluorescent nanoparticle imaging probe having a switching function (a function to quench a fluorescent dye in a blood component and emit fluorescence in a tumor or an inflamed site to be imaged). [Solution] A fluorescent nanoparticle probe comprising: a molecular assembly composed of an amphiphilic block polymer having a hydrophilic block chain and a hydrophobic block chain; and a fluorescent dye encapsulated in the assembly, wherein (a) the hydrophilic block chain comprises, as an essential hydrophilic structural unit, a unit selected from a sarcosine unit and an alkylene oxide unit, (b) the hydrophobic block chain comprises, as an essential hydrophobic structural unit, a unit selected from the group consisting of an amino acid unit and a hydroxylic acid unit, and (c) the fluorescent dye is a polylactic acid-bound cyanine compound comprising: a fluorescent group represented by the formula (I): ##STR00001##
and a polylactic acid group having 5 to 50 lactic acid units, and two or more molecules of the fluorescent dye are encapsulated in the single molecular assembly.

Encompassed are embodiments of activatable nanoprobes useful for in vivo longitudinal imaging of drug hepatotoxicity with oxidative and nitrosative stress as the safety biomarkers. Both H.sub.2O.sub.2 and ONOO.sup.− are important mediators of radical stress. Two channels of optical detection, intrinsically free from cross-talk, were engineered into superconducting polymer nanoparticles to generate chemiluminescence resonance energy transfer between the conjugated polymer matrix of the nanoparticle and an incorporated chemiluminescent substrate allowing for the luminescent detection of H.sub.2O.sub.2 and fluorescence resonance energy transfer between the polymer matrix and an oxidation-degradable fluorophore for ratiometric detection of ONOO These nanoprobes have been applied for real-time in vivo monitoring of hepatotoxicity resulting from challenges from drugs. In addition to the ability of imaging the dose-dependence of oxidative and nitrosative stress, the positive detection of radical stress that precedes histological changes allow the early and longitudinal detection of drug-induced hepatotoxicity in vivo.

This application relates to nanoparticles, including nanoparticles derived from a plasma, and their use in the formation of conjugates. The nanoparticles can be stably conjugated to a wide variety of second species, forming conjugates which can be used, for example, in therapeutic, diagnostic and experimental methods.

Disclosed are branched PEG molecules, including branched PEG-lipids and branched-PEG proteins, as well as related compositions and methods for making branched PEG molecules. Also disclosed are related compositions, systems, and methods for in vivo delivery of therapeutic and diagnostic agents.

The present invention includes a vanillyl alcohol-containing copolyoxalate copolymer (PVAX). The present invention also includes a PVAX microparticle comprising PVAX. In one aspect, the compositions of the invention can be used as a drug delivery system, an antioxidant or anti-inflammatory composition, a composition for preventing or treating ischemic disease, a composition for inhibiting the side effects of anticancer drugs, a contrast agent, and/or a composition for diagnosing ischemic disease.