MALDI-MS Imaging Analysis of Noninflammatory Type III Rotaxane Dendrimers

Tao Wang, Zongwei CAI, Yanyan Chen, Wang Ka Lee, Chak Shing Kwan, Min LI, Albert S.C. Chan, Zhi Feng Chen, Ka Loon Allen CHEUNG, Ken C F LEUNG*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Rotaxane dendrimers with hyperbranched macromolecular interlocked structures and size modulation capacity demonstrate drug binding and release ability upon external stimuli. Mass spectrometry imaging (MSI) can offer the high-throughput screening of endogenous/exogenous compounds. Herein, we reported a novel method to display the in situ spatial distribution of label-free monodispersed type III rotaxane dendrimers (RDs) G1 (first generation, size ∼1.5 nm) and G2 (second generation, size ∼5 nm) that were explored as potential drug vehicles in spleen tissue by using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-MSI). Experimental results indicated that the trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene]malononitrile (DCTB) matrix exhibited the best performance for monodispersed type III RDs G1 and G2. The optimized method was successfully applied to map the in vivo spatial distribution of type III RDs G1 and G2 in the spleen from intraperitoneally injected mice. The MALDI-MSI images revealed that RDs G1 and G2 were relatively stable in the spleen within 24 h after administration. It was found that the identified type III RDs G1 and G2 penetrated through the tunica serosa and were predominantly localized in red pulp regions of spleens. They were also mapped in a marginal zone of spleens simultaneously. There was almost no toxicity of type III RDs G1 and G2 to mice spleens from the H&E results. Furthermore, the type III RDs did not induce the expression of inflammatory cytokines from peripheral blood mononuclear cells (PBMCs) or THP-1 monocytes. The MSI analysis not only demonstrated its ability to image select rotaxane dendrimers in a rapid and efficient manner but also provided tremendous assistance on the applications of the further treatment of cancerous tissue as safe drug carriers. Furthermore, the new strategy demonstrated in this study could be applied on other label-free mechanically interlocked molecules, molecular machines, and macromolecules, which opened a new path to evaluate the toxicological and pharmacokinetic characteristics of these novel materials at the suborgan level.

Original languageEnglish
Pages (from-to)2488-2494
Number of pages7
JournalJournal of the American Society for Mass Spectrometry
Volume31
Issue number12
DOIs
Publication statusPublished - 2 Dec 2020

Scopus Subject Areas

  • Structural Biology
  • Spectroscopy

User-Defined Keywords

  • dendrimer
  • label-free
  • MALDI mass spectrometry imaging
  • spatial distribution
  • tissue imaging

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