Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-muscle invasive bladder cancer is one of the most frequent forms of cancer. Commonly, the superficial tumor is removed by a minimal invasive surgery, mostly followed by the intravesical instillation of cytostatic agents. Although the initial treatment is usually successful, the recurrence rate is extraordinary high, which might be grounded in limiting factors during instillation, such as the high resistance of the bladder wall and the constant dilution with the permanently produced urine reducing the probability of interaction between the drug and the target cell. To overcome these limitations, we introduce a lectin-mediated drug delivery system consisting of wheat germ agglutinin as targeter, poly-l-glutamic acid as backbone and the active pharmaceutical ingredient (API) doxorubicin that should prolong the residence time in the bladder cavity. The optimized WGA-PGA-Doxo conjugate revealed an API load of 81 molecules per mole backbone and convinced in urothelial cell monolayer studies with an up to 56-fold higher cell-binding potential than pure doxorubicin. Additionally, the highly substituted drug delivery system not only internalized into urothelial cells, but also inhibited cell viability up to 99%. The combination of the high drug load with the promising cell-associative properties, which also revealed a higher affinity to malignant than to healthy urothelial cells, and the proven cytotoxic potential might lead to an improved efficacy of intravesical chemotherapy.
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PMID:A doxorubicin loaded colloidal delivery system for the intravesical therapy of non-muscle invasive bladder cancer using wheat germ agglutinin as targeter. 2996 15

Animal models are effective for assessing tumor localization of nanosystems but difficult to use for studying penetration beyond the vasculature. Here, we have used well-characterized HCT116 colorectal cancer spheroids to study the effect of nanoparticle (NP) physicochemical properties on penetration and uptake. Incubation of spheroids with Hoechst 33342 resulted in a dye gradient, which facilitated discrimination between the populations of cells in the core and at the periphery of spheroids by flow cytometry. This approach was used to compare doxorubicin and liposomal doxorubicin (Caelyx) and a range of model poly(styrene) nanoparticles of different sizes (30 nm, 50 nm, 100 nm) and with different surface chemistries (50 nm uniform plain, carboxylated, aminated and a range of NPs and polyethylene glycol modified NPs prepared from a promising new functionalized biodegradable polymer (poly(glycerol-adipate), PGA). Unmodified poly(styrene) nanoparticles (30 nm/50 nm) were able to penetrate to the core of HCT116 spheroids more efficiently than larger poly(styrene) nanoparticles (100 nm). Surprisingly, penetration of 30 and 50 nm particles was as good as clinically relevant doxorubicin concentrations. However, penetration was reduced with higher surface charge. PGA NPs of 100 nm showed similar penetration into spheroids as 50 nm poly(styrene) nanoparticles, which may be related to polymer flexibility. PEG surface modification of polymeric particles significantly improved penetration into the spheroid core. The new model combining the use of spheroids Hoechst staining and flow cytometry was a useful model for assessing NP penetration and gives useful insights into the effects of NPs' physical properties when designing nanomedicines.
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PMID:Penetration and Uptake of Nanoparticles in 3D Tumor Spheroids. 3094 70