Selective targeting and therapy of metastatic and multidrug resistant tumors using a long circulating podophyllotoxin nanoparticle.

ABSTRACT: Treatment options for metastatic and multidrug resistant (MDR) tumors are limited, and most of the chemotherapeutic drugs exhibit low efficacy against MDR cancers. An anti-tubulin agent podophyllotoxin (PPT) displays high potency against MDR tumor cells. However, due to its poor solubility and non-specificity, PPT cannot be used systemically. We have developed a self-assembling nanoparticle dosage form for PPT (named Celludo) by covalently conjugating PPT and polyethylene glycol (PEG) to acetylated carboxymethyl cellulose (CMC-Ac) via ester linkages. Celludo displayed extended blood circulation with an 18-fold prolonged half-life (t_1/2), 9000-fold higher area under the curve (AUC), and 1000-fold reduced clearance compared to free PPT. Tumor delivery was 500-fold higher in the Ce

SUBMITTER: Roy A 

PROVIDER: S-EPMC5516947 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature