Co-Encapsulation of Doxorubicin With Galactoxyloglucan Nanoparticles for Intracellular Tumor-Targeted Delivery in Murine Ascites and Solid Tumors

摘要

Doxorubicin (Dox) treatment is limited by severe toxicity and frequent episodes of treatment failure. To minimize adverse events and improve drug delivery efficiently and specifically in cancer cells, encapsulation of Dox with naturally obtained galactoxyloglucan polysaccharide (PST001), isolated from Tamarindus indica was attempted. Thus formed PST-Dox nanoparticles induced apoptosis and exhibited significant cytotoxicity in murine ascites cell lines, Dalton’s lymphoma ascites and Ehrlich’s ascites carcinoma. The mechanism contributing to the augmented cytotoxicity of nanoconjugates at lower doses was validated by measuring the Dox intracellular uptake in human colon, leukemic and breast cancer cell lines. PST-Dox nanoparticles showed rapid internalization of Dox into cancer cells within a short period of incubation. Further, in vivo efficacy was tested in comparison to the parent counterparts - PST001 and Dox, in ascites and solid tumor syngraft mice models. Treatment of ascites tumors with PST-Dox nanoparticles significantly reduced the tumor volume, viable tumor cell count, and increased survival and percentage life span in the early, established and prophylactic phases of the disease. Administration of nanoparticles through intratumoral route delivered more robust antitumor response than the intraperitoneal route in solid malignancies. Thus, the results indicate that PST-Dox nanoparticles have greater potential compared to the Dox as targeted drug delivery nanocarriers for loco regional cancer chemotherapy applications.