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Biomaterials. 2015 Jan;37:456-468. doi: 10.1016/j.biomaterials.2014.10.044. Epub 2014 Oct 31.

Telodendrimer nanocarrier for co-delivery of paclitaxel and cisplatin: A synergistic combination nanotherapy for ovarian cancer treatment.

Cai L#1,2, Xu G#1,3, Shi C1, Guo D1, Wang X1, Luo J1.

Author information

1
Department of Pharmacology, SUNY Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
2
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei 430022, China.
3
Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.
#
Contributed equally

Abstract

Cisplatin (CDDP) and paclitaxel (PTX) are two established chemotherapeutic drugs used in combination for the treatment of many cancers, including ovarian cancer. We have recently developed a three-layered linear-dendritic telodendrimer micelles (TM) by introducing carboxylic acid groups in the adjacent layer via "thio-ene" click chemistry for CDDP complexation and conjugating cholic acids via peptide chemistry in the interior layer of telodendrimer for PTX encapsulation. We hypothesize that the co-delivery of low dosage PTX with CDDP could act synergistically to increase the treatment efficacy and reduce their toxic side effects. This design allowed us to co-deliver PTX and CDDP at various drug ratios to ovarian cancer cells. The in vitro cellular assays revealed strongest synergism in anti-tumor effects when delivered at a 1:2 PTX/CDDP loading ratio. Using the SKOV-3 ovarian cancer xenograft mouse model, we demonstrate that our co-encapsulation approach resulted in an efficient tumor-targeted drug delivery, decreased cytotoxic effects and stronger anti-tumor effect, when compared with free drug combination or the single loading TM formulations.

KEYWORDS:

Cisplatin; Combination chemotherapy; Drug delivery; Ovarian cancer; Paclitaxel; Synergism

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