Extravasation into tumors

Small pegylated liposomes have been shown to extravasate into tumors with leaky vasculature, and the prolonged circulation half-life has a positive effect on the extravasation. Passive tumor targeting of liposomes was visualized in a study of radio-labeled PEG-liposomes in patients with locally advanced cancers, and whole body gamma camera imaging was used to monitor biodistribution and tumor localization. Of 17 patients treated with In-DTPA (Diethylenetri-aminepentaacetic acid) labeled PEG-liposomes, tumor... 

Nanoparticles such as those of the heavy metals, like cadmium selenide, cadmium sulfide, lead sulfide, and cadmium telluride are potentially toxic [14,15]. The possible mechanisms by which nanoparticles cause toxicity inside cells are schematically shown in Fig. 2. They need to be coated or capped with low toxicity or nontoxic organic molecules or polymers (e.g., PEG) or with inorganic layers (e.g., ZnS and silica) for most of the biomedical applications. In fact, many biomedical imaging and detection applications of QDs encapsulated by complex molecules do not exhibit noticeable toxic effects [16]. One report shows that the tumor cells labeled with QDs survived in circulation and extravasated into tissues... 

Extravasation of tumor cells through blood vessel wall into secondary organ, and... 

Sufficient stable loading of drug in order to reach disease site with liposomes loaded with drug at a level needed to achieve therapeutic efficacy Extravasation into diseased tissue (tumor or inflamed sites)... 

Microspheres are particles ranging between 1 and 100 pm. They are typically formed from degradable polymeric materials such as albumin, polysaccharides, or poly(a-hydroxy acids) by precipitation or phase-separation emulsion techniques [6, 332]. The relatively large diameters of microspheres make their extravasation into the tumor mass difficult and the uptake of microspheres by the RES is very rapid. 

The biochemical alterations which provide malignant cells with the ability to invade adjacent tissues and to spread to other locations are poorly understood and are undoubtedly complex. This complexity manifests itself clearly in the process of metastasis, in which cells must go through a series of steps including tissue invasion, extravasation into blood vessels, thrombus formation, arrest, penetration through the wall of a lood vessel and growth, all in order to develop a secondary tumor. Each step of this sequence may require the precise temporal expression of specific biochemical functions, and some of these reactions, necessary for a step such as invasion, may be detrimental to other steps, such as the formation of a thrombus and arrest. 

Maruyama, K., et al., Immunoliposomes bearing polyethyleneglycol-coupled Fab fragment show prolonged circulation time and high extravasation into targeted solid tumors in vivo, FEBS Letters, 413(1) 177-180(1997). 

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