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Tumor-Targeting Micelles Based on Linear-Dendritic PEGPTX8 Conjugate for Triple Negative Breast Cancer Therapy Yujie Zhang, Yifei Lu, Yu Zhang, Xi He, Qinjun Chen, Lisha Liu, Xinli Chen, Chunhui Ruan, Tao Sun, and Chen Jiang Mol. Pharmaceutics, Just Accepted Manuscript • DOI: 10.1021/acs.molpharmaceut.7b00430 • Publication Date (Web): 23 Aug 2017 Downloaded from http://pubs.acs.org on August 24, 2017
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Molecular Pharmaceutics
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Tumor-Targeting Micelles Based on Linear-
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Dendritic PEG-PTX8 Conjugate for Triple
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Negative Breast Cancer Therapy
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Yujie Zhang, Yifei Lu, Yu Zhang, Xi he, Qinjun Chen, Lisha Liu, Xinli Chen,
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Chunhui Ruan, Tao Sun, Chen Jiang*
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Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key
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Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of
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Pharmacy, Fudan University, Shanghai 200032, China
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Corresponding author: Chen Jiang, Tel: +86-21-5198-0079; Fax: +86-21-5198-
0079; E-mail:
[email protected]. 1 ACS Paragon Plus Environment
Molecular Pharmaceutics
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Table of Contents/Abstract Graphic
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KEYWORDS: polymer-drug conjugates, linear-dendritic, micelle, triple negative breast cancer,
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tumor targeting
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ABSTRACT: Most small molecular chemotherapeutics have poor water-solubility, unexpected
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pharmacokinetics and toxicity to normal tissues. A series of nano drug delivery systems have
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been developed to solve the problems, among which micelle based on linear-dendritic polymer-
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drug conjugates (LDPDCs) is a promising strategy to deliver hydrophobic chemotherapeutics
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due to its small size, fine stability in blood circulation and high drug loading capacity. In this
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work we synthesized a novel amphiphilic linear-dendritic PEG-PTX8 conjugate which can also
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encapsulate extra free PTX and self-assemble into uniform ultra-small micelles with a hydrated
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diameter of 25.50±0.27 nm. To realize efficient drug delivery to tumor sites, a cyclic tumor
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homing and penetrating peptide iNGR was linked to the PEG-PTX8 conjugate. The biological
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evaluation was performed on a human triple negative breast cancer model. PTX accumulation in
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tumor at 24 h of the TNBC-bearing mice treated with iNGR-PEG-PTX8/PTX micelles was
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significantly enhanced (P
