Next Article in Journal
Poly(lactide-co-glycolide)/Hydroxyapatite Porous Scaffold with Microchannels for Bone Regeneration
Next Article in Special Issue
Stimuli-Responsive Block Copolymer-Based Assemblies for Cargo Delivery and Theranostic Applications
Previous Article in Journal
Polybenzoxazine/Polyhedral Oligomeric Silsesquioxane (POSS) Nanocomposites
Article Menu
Issue 6 (June) cover image

Export Article

Open AccessArticle
Polymers 2016, 8(6), 226; doi:10.3390/polym8060226

pH-Responsive Tumor-Targetable Theranostic Nanovectors Based on Core Crosslinked (CCL) Micelles with Fluorescence and Magnetic Resonance (MR) Dual Imaging Modalities and Drug Delivery Performance

Chinese Academy of Sciences Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, China
*
Author to whom correspondence should be addressed.
Academic Editor: Sebastien Lecommandoux
Received: 18 April 2016 / Revised: 30 May 2016 / Accepted: 2 June 2016 / Published: 7 June 2016
View Full-Text   |   Download PDF [3275 KB, uploaded 7 June 2016]   |  

Abstract

The development of novel theranostic nanovectors is of particular interest in treating formidable diseases (e.g., cancers). Herein, we report a new tumor-targetable theranostic agent based on core crosslinked (CCL) micelles, possessing tumor targetable moieties and fluorescence and magnetic resonance (MR) dual imaging modalities. An azide-terminated diblock copolymer, N3-POEGMA-b-P(DPA-co-GMA), was synthesized via consecutive atom transfer radical polymerization (ATRP), where OEGMA, DPA, and GMA are oligo(ethylene glycol)methyl ether methacrylate, 2-(diisopropylamino)ethyl methacrylate, and glycidyl methacrylate, respectively. The resulting diblock copolymer was further functionalized with DOTA(Gd) (DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakisacetic acid) or benzaldehyde moieties via copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) chemistry, resulting in the formation of DOTA(Gd)-POEGMA-b-P(DPA-co-GMA) and benzaldehyde-POEGMA-b-P(DPA-co-GMA) copolymers. The resultant block copolymers co-assembled into mixed micelles at neutral pH in the presence of tetrakis[4-(2-mercaptoethoxy)phenyl]ethylene (TPE-4SH), which underwent spontaneous crosslinking reactions with GMA residues embedded within the micellar cores, simultaneously switching on TPE fluorescence due to the restriction of intramolecular rotation. Moreover, camptothecin (CPT) was encapsulated into the crosslinked cores at neutral pH, and tumor-targeting pH low insertion peptide (pHLIP, sequence: AEQNPIYWARYADWLFTTPLLLLDLALLVDADEGTCG) moieties were attached to the coronas through the Schiff base chemistry, yielding a theranostic nanovector with fluorescence and MR dual imaging modalities and tumor-targeting capability. The nanovectors can be efficiently taken up by A549 cells, as monitored by TPE fluorescence. After internalization, intracellular acidic pH triggered the release of loaded CPT, killing cancer cells in a selective manner. On the other hand, the nanovectors labeled with DOTA(Gd) contrast agents exhibited increased relaxivity (r1 = 16.97 mM−1·s−1) compared to alkynyl-DOTA(Gd) small molecule precursor (r1 = 3.16 mM−1·s−1). Moreover, in vivo MRI (magnetic resonance imaging) measurements revealed CCL micelles with pHLIP peptides exhibiting better tumor accumulation and MR imaging performance as well. View Full-Text
Keywords: pH-responsive; tumor targeting; aggregation induced emission; MR imaging; pHLIP pH-responsive; tumor targeting; aggregation induced emission; MR imaging; pHLIP
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Tian, S.; Liu, G.; Wang, X.; Zhang, G.; Hu, J. pH-Responsive Tumor-Targetable Theranostic Nanovectors Based on Core Crosslinked (CCL) Micelles with Fluorescence and Magnetic Resonance (MR) Dual Imaging Modalities and Drug Delivery Performance. Polymers 2016, 8, 226.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Polymers EISSN 2073-4360 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top