|
Glioblastoma is one of the most aggressive forms of brain cancer . Rather than presenting as a well-defined tumor, glioblastoma willoften infiltrate the surrounding brain tissue, making it extremelydifficult to treat surgically or with chemotherapy or radiation.Likewise, several mouse models of glioblastoma have provencompletely resistant to all treatment attempts. In a new study, ateam led by scientists at Sanford-Burnham Medical ResearchInstitute (Sanford-Burnham) and the Salk Institute for BiologicalStudies developed a method to combine a tumor-homing peptide, acell-killing peptide, and a nanoparticle that both enhances tumorcell death and allows the researchers to image the tumors. Whenused to treat mice with glioblastoma, this new nanosystemeradicated most tumors in one model and significantly delayed tumordevelopment in another. These findings were published the week ofOctober 3 in the Proceedings of the National Academy of Sciences of the USA. "This is a unique nanosystem for two reasons. First, linking thecell-killing peptide to nanoparticles made it possible for us todeliver it specifically to tumors, virtually eliminating the killerpeptide's toxicity to normal tissues. Second, ordinarilyresearchers and clinicians are happy if they are able to delivermore drugs to a tumor than to normal tissues. We not onlyaccomplished that, but were able to design our nanoparticles todeliver the killer peptide right where it acts - the mitochondria,the cell's energy-generating center," said Erkki Ruoslahti, M.D.,Ph.D., senior author of the study and distinguished professor inboth Sanford-Burnham's NCI-designated Cancer Center in La Jolla andthe Center for Nanomedicine, a Sanford-Burnham collaboration withthe University of California, Santa Barbara. The nanosystem developed in this study is made up of threeelements. First, a nanoparticle acts as the carrier framework foran imaging agent and for two peptides (short proteins). One ofthese peptides guides the nanoparticle and its payload specificallyto cancer cells and the blood vessels that feed them by bindingcell surface markers that distinguish them from normal cells. Thissame peptide also drives the whole system inside these targetcells, where the second peptide wreaks havoc on the mitochondria,triggering cellular suicide through a process known as apoptosis. Together, these peptides and nanoparticles proved extremelyeffective at treating two different mouse models of glioblastoma.In the first model, treated mice survived significantly longer thanuntreated mice. In the second model, untreated mice survived foronly eight to nine weeks. In sharp contrast, treatment with thisnanosystem cured all but one of ten mice. What's more, in additionto providing therapy, the nanoparticles could aid in diagnosingglioblastoma; they are made of iron oxide, which makes them - andtherefore the tumors they target - visible by MRI, the sametechnique already used to diagnose many health conditions. In a final twist, the researchers made the whole nanosystem evenmore effective by administering it to the mice in conjunction witha third peptide. Dr. Ruoslahti and his team previously showed thatthis peptide, known as iRGD, helps co-administered drugs penetratedeeply into tumor tissue. iRGD has been shown to substantiallyincrease treatment efficacy of various drugs against human breast,prostate, and pancreatic cancers in mice, achieving the same therapeutic effect as a normal dosewith one-third as much of the drug. Here, iRGD enhancednanoparticle penetration and therapeutic efficacy. "In this study, our patients were mice that developed glioblastomaswith the same characteristics as observed in humans with thedisease. We treated them systemically with the nanoparticles. Oncethe nanoparticles reached the tumors' blood vessels, they deliveredtheir payload (a drug) directly to the cell's power producer, themitochondria. By destroying the blood vessels and also somesurrounding tumor cells, we were able to cure some mice and extendthe lifespan of the rest," said Dinorah Friedmann-Morvinski, Ph.D.,co-first author of the study and post-doctoral research associatein the laboratory of Inder Verma, Ph.D. at the Salk Institute. Additional References Citations. We are high quality suppliers, our products such as Elight Hair Removal , RF Beauty Machine for oversee buyer. To know more, please visits ipl Laser Equipment.
Related Articles -
Elight Hair Removal, RF Beauty Machine,
|
