PLGA-amine from PolySciTech used in development of doxorubicin delivery for bone cancer therapy

 

Bone cancer is difficult to treat due to the poor vascularization and drug delivery in bone tissue. Researchers from Seoul National University used PLGA-NH2 (Cat# AI017) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create alendronate-decorated PLGA-chondroitin sulfate particles for bone-tissue targeting. This research holds promise to improve treatments for this potentially fatal disease. Read more: Kang, Nae-Won, Voradanu Visetvichaporn, Duy-Thuc Nguyen, Da-Han Kim, Min-Jae Kim, So-Yeol Yoo, Jae-Young Lee, and Dae-Duk Kim. "Bone Tumor-Homing Nanotherapeutics for Prolonged Retention in Tumor Microenvironment and Facilitated Apoptotic Process Via Mevalonate Pathway Inhibition." Available at SSRN 4155152. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4155152

“Bone malignancy features a mineralized extracellular matrix primarily composed of hydroxyapatite, which interferes with the distribution and activity of antineoplastic agents. Herein, we report bone tumor-homing polymeric nanotherapeutics consisting of alendronate-decorated chondroitin sulfate A-graft-poly(lactide-co-glycolide) and doxorubicin (DOX), named PLCSA-AD, which displayed a prolonged retention profile in the tumor microenvironment and augmented therapeutic efficacy via inhibition of the mevalonate pathway. PLCSA-AD exhibited a 1.72-fold lower IC50 value than free DOX and a higher affinity for hydroxyapatite than PLCSA in HOS/MNNG cell-based 2D bone tumor-mimicking models. The inhibition of the mevalonate pathway by PLCSA-AD in tumor cells was verified by investigating the cytosolic fraction of unprenylated proteins, where blank PLCSA-AD significantly increased the expression of cytosolic Ras and RhoA without changing their total cellular amounts. In a bone tumor-mimicking xenografted mouse model, AD-decorated nanotherapeutics significantly increased tumor accumulation (1.73-fold) compared with PLCSA, and higher adsorption to hydroxyapatites was observed in the histological analysis of the tumor. As a result, inhibition of the mevalonate pathway and improvement in tumor accumulation led to markedly enhanced therapeutic efficacy in vivo, suggesting that PLCSA-AD could be promising nanotherapeutics for bone tumor treatment. Keywords: bone tumors, alendronate, mevalonate pathway inhibition, hydroxyapatites, tumor distribution, apoptosis”