We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
INTEGRA BIOSCIENCES AG

Download Mobile App




Cells Loaded with Prodrug-Containing Microparticles Selectively Destroy Prostate Cancer Tumors

By LabMedica International staff writers
Posted on 02 May 2016
Print article
Image: A confocal microscopy image of stem cells loaded with drug containing polymeric microparticles (Photo courtesy of Jeff Karp and Oren Levy, Brigham and Women\'s Hospital).
Image: A confocal microscopy image of stem cells loaded with drug containing polymeric microparticles (Photo courtesy of Jeff Karp and Oren Levy, Brigham and Women\'s Hospital).
A novel approach to treating metastatic prostate cancer with minimal adverse side effects is based on cellular transport of a harmless prodrug that is activated and becomes toxic only in the vicinity of the tumor microenvironment.

Investigators at Brigham and Women's Hospital (Boston, MA, USA) and colleagues at Johns Hopkins University (Baltimore, MD, USA) loaded human mesenchymal stem cells (MSCs) with poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) that encapsulated the macromolecule G114, a thapsigargin-based prodrug that was specifically activated by prostate specific antigen (PSA).

Thapsigargin, a sesquiterpene lactone extracted from a plant, Thapsia garganica is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase. The drug raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticula. Thapsigargin specifically inhibits the fusion of autophagosomes with lysosomes; the last step in the autophagic process. The inhibition of the autophagic process in turn induces stress on the endoplasmic reticulum, which ultimately leads to cellular death.

The investigators reported in the March 17, 2016, online edition of the journal Biomaterials that G114-particles (approximately 950 nanometers in size) were internalized by MSCs, followed by the release of G114 as an intact prodrug from the loaded cells. G114 released from G114 MP-loaded MSCs selectively induced death of the PSA-secreting prostate cancer cell line, LNCaP.

G114 MP-loaded MSCs inhibited tumor growth when used in proof-of-concept co-inoculation studies with CWR22 prostate cancer xenografts, suggesting that cell-based delivery of G114 did not compromise the potency of this pro-drug in vitro or in vivo.

"The prodrug only becomes toxic in the presence of the tumor microenvironment, which adds another layer of specificity to this targeted delivery system," said contributing author Dr. John Isaacs, professor of urology and oncology at Johns Hopkins University.

"In cancer therapeutics, one of the great challenges is finding how to specifically deliver high doses of chemotherapeutics to a tumor, but minimize the systemic toxicity," said senior author Dr. Jeffrey Karp, associate professor of medicine at Brigham and Women's Hospital.

Related Links:
Brigham and Women's Hospital
Johns Hopkins University
Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
Specimen Collection & Transport
Complement 3 (C3) Test
GPP-100 C3 Kit
New
Gold Member
Fully Automated Cell Density/Viability Analyzer
BioProfile FAST CDV

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: MOF materials efficiently enrich cfDNA and cfRNA in blood through simple operational process (Photo courtesy of Science China Press)

Blood Circulating Nucleic Acid Enrichment Technique Enables Non-Invasive Liver Cancer Diagnosis

The ability to diagnose diseases early can significantly enhance the effectiveness of clinical treatments and improve survival rates. One promising approach for non-invasive early diagnosis is the use... Read more

Hematology

view channel
Image: The low-cost portable device rapidly identifies chemotherapy patients at risk of sepsis (Photo courtesy of 52North Health)

POC Finger-Prick Blood Test Determines Risk of Neutropenic Sepsis in Patients Undergoing Chemotherapy

Neutropenia, a decrease in neutrophils (a type of white blood cell crucial for fighting infections), is a frequent side effect of certain cancer treatments. This condition elevates the risk of infections,... Read more

Pathology

view channel
Image: The OvaCis Rapid Test discriminates benign from malignant epithelial ovarian cysts (Photo courtesy of INEX)

Intra-Operative POC Device Distinguishes Between Benign and Malignant Ovarian Cysts within 15 Minutes

Ovarian cysts represent a significant health issue for women globally, with up to 10% experiencing this condition at some point in their lives. These cysts form when fluid collects within a thin membrane... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.