The impact of enzymatic degradation on the uptake of differently sized therapeutic molecules.

Background: The extracellular matrix represents a major barrier for drug delivery. This work compares the effects of collagenase and hyaluronidase on tumour uptake and distribution of two differently sized therapeutic molecules, IgG and liposomal doxorubicin.

Materials And Methods: The enzymes were injected i.

Diffusion measured by fluorescence recovery after photobleaching based on multiphoton excitation laser scanning microscopy.

Fluorescence recovery after photobleaching (FRAP) is a widely used method to measure diffusion. The technique is normally based on one-photon excitation, which limits diffusion to two dimensions due to extended photobleaching in the axial direction. Multiphoton excitation, on the other hand, creates a well-defined focal volume.

Second-harmonic generation in collagen as a potential cancer diagnostic parameter.

The fibrillar collagen network in tumor and normal tissues is different due to remodeling of the extracellular matrix during the malignant process. Collagen type I fibers have the crystalline and noncentrosymmetric properties required for generating the second-harmonic signal. The content and structure of collagen were studied by imaging the second-harmonic generation (SHG) signal in frozen sections from three tumor tissues, osteosarcoma, breast carcinoma, and melanoma, and were compared with corresponding normal tissues, bone/femur, breast, and dermis/skin.

Physical and chemical modifications of collagen gels: impact on diffusion.

The extracellular matrix (ECM) represents a major barrier for delivery of therapeutic drugs, and the transport is determined by the ECM composition, structure, and distribution. Because of the high interstitial fluid pressure in tumors, diffusion becomes the main transport mechanism through ECM. The purpose of this work was to study the impact of the structure of the collagen network on diffusion, by studying to what extent the orientation and chemical modification of the collagen network influenced diffusion.

Quantification of the second-order nonlinear susceptibility of collagen I using a laser scanning microscope.

Characteristic changes in the organization of fibrillar collagen can potentially serve as an early diagnostic marker in various pathological processes. Tissue types containing collagen I can be probed by pulsed high-intensity laser radiation, thereby generating second harmonic light that provides information about the composition and structure at a microscopic level. A technique was developed to determine the essential second harmonic generation (SHG) parameters in a laser scanning microscope setup.