Synthesis of a targeted, dual pH and redox-responsive nanoscale coordination polymer theranostic against metastatic breast cancer in vitro and in vivo

ABSTRACT

Background

Nanoscale coordination polymers (nCP) have exhibited a great potential in designing of the theranostic platforms in the latest years. However, they have low selectivity for cancerous tissues and require to be modified for becoming effective cancer therapeutics. In this study, a novel nanoscale pH and redox-responsive coordination polymer with high selectivity was synthesized.

Methods

The nCP was synthesized by iron(III) chloride and dithiodiglycolic acid. After loading the prepared nCP with doxorubicin (DOX), nCP was coated with an amphiphilic copolymer composed of α-tocopheryl succinate-polyethylene glycol (VEP). Next, AS1411 aptamer was decorated on the VEP shell of the DOX-loaded nCP (Apt-VEP-nCP@DOX) to provide a guided drug delivery platform.

Results

The prepared platform demonstrated high DOX loading capacity and pH and redox-responsive DOX release. Apt-VEP-nCP@DOX displayed greater DOX internalization and toxicity toward breast cancer cells of 4T1 and MCF7 compared with that of non-targeted VEP-nCP@DOX. Also, the intravenous injection of Apt-VEP-nCP@DOX (a single dose) considerably suppressed the 4T1 tumor growth in vivo. Moreover, Apt-VEP-nCP@DOX showed outstanding magnetic resonance (MR) imaging capability for 4T1 adenocarcinoma diagnosis in ectopic 4T1 tumor model in mice.

Conclusions

The developed innovative intelligent Apt-VEP-nCP@DOX could serve as a safe and biocompatible theranostic platform appropriate for further translational purposes against breast cancer.

KEYWORDS:

• Nano coordination polymer
• theranostics
• doxorubicin
• breast cancer
• dithiodiglycolic acid
• magnetic resonance imaging
• AS1411 aptamer

Author contributions

Monireh Falsafi: Methodology, Investigation, Data curation, Formal analysis, Validation, Writing - original draft. Naeimeh Hassanzadeh Goji: Formal analysis, Visualization. Amir Sh. Saljooghi: Formal analysis, Writing - review & editing. Khalil Abnous: Investigation. Seyed Mohammad Taghdisi: Investigation & visualization, Sirous Nekooei: MRI imaging, Mohammad Ramezani: Supervision. Mona Alibolandi: Funding acquisition, Methodology, Project administration, Conceptualization, Supervision. All authors approve the final version of the manuscript to be published; and that all authors agree to be accountable for all aspects of the work.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

The authors greatly appreciate the support of Mashhad University of Medical Sciences (Grant no: 981365).