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

Biomaterials
Aniruddha RoyShyh-Dar Li

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 (t1/2), 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 Cellduo group compared to free PPT. Against the lung metastatic model of EMT6-AR1, Celludo showed selective localization in the metastatic nodules and increased the median survival to 20 d compared to 6-8 d with docetaxel and PPT treatment. In the intraperitoneal metastatic model of human ovarian NCI-ADR/RES tumor, Celludo prolonged the median survival from 50 d to 70 d, whereas the standard therapy PEGylated liposomal doxorubicin showed no effect. No majo...Continue Reading

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Citations

Sep 10, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yongfei LiChang Yao
Oct 6, 2020·Macromolecular Bioscience·Anna E CaprificoGianpiero Calabrese
Feb 8, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Xiu ZhaoLijuan Chen
Apr 23, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Luzhou XuJun Cheng
May 18, 2021·Asian Journal of Pharmaceutical Sciences·Qiu WangJin Sun
Aug 28, 2021·Frontiers in Cell and Developmental Biology·Hua-Yang FanXin-Hua Liang

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