Polymeric dipicolylamine based mass tags for mass cytometry

Zhang, Yefeng; Liu, Peng; Majonis, Daniel; Winnik, Mitchell A.

doi:10.1039/d2sc00595f

Cited by 13 publications

(19 citation statements)

References 49 publications

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“…Recently, Ding group exploited Zr‐NMOFs for labeling lymphocytes (CD45 + ) in PBMCs [21] . Winnik group demonstrated the efficacy of MCP‐based mass tags for identifying T cells (CD45 + CD3 + ) and B cells (CD45 + CD3 − CD20 + ) from lymphocytes [12] . Here, we performed immunophenotyping of PBMCs for identifying CD4 + T helper (Th), CD8 + cytotoxic T lymphocyte (CTL), B, NK, and NKT subsets.…”

Section: Resultsmentioning

confidence: 99%

“…The sensitivity of MCP‐based CyTOF markers is limited by the total amounts of metals that can be chelated onto the polymer sidechains [4, 5] . More importantly, only a limited number of metals including Ln, [3, 8] Y, [3] In, [9] Bi, [10] Cd, [11] Pt [12] and Re [12] have been demonstrated in the MCP systems with effective CyTOF performance. Attempts to load more types of metals in MCPs have also been problematic due to the cross‐linking between polymer chains [22] and the potential interference with the antibodies for antigen recognition [3, 22] .…”

Section: Introductionmentioning

confidence: 99%

“…Current design strategies for CyTOF markers include metal-chelating polymers (MCP), [3][4][5][6][7][8][9][10][11][12][13] nanoscale aggregates of noble metals, [14,15] inorganic nanoparticles (NPs), [16][17][18][19][20] and coordinated metal-containing clusters. [21] However, these approaches still face difficulties in resolving the limited multiplexing capability of CyTOF.…”

Section: Introductionmentioning

confidence: 99%

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Metal‐Chelatable Porphyrinic Frameworks for Single‐Cell Multiplexing with Mass Cytometry

Chen

Wang

Wang³

et al. 2022

Angewandte Chemie

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Single-cell multiplexing is key to exploration of the heterogeneous cell populations in biological systems. Although the state-of-the-art mass cytometry (CyTOF) possesses high resolution and multiple dimensions, the lack of suitable marker materials prohibits fully exploiting the available CyTOF detection channels.Here we report a new design strategy for CyTOF markers using functionalized mesoporous porphyrinic frameworks (MPFs) as scaffolds for chelating metals that have been unachievable by conventional approaches. We developed surface modification for stably dispersing the MPF nanoparticles (< 40 nm) during the metalation and antibody conjugation processes. Our markers exhibit higher sensitivity and comparable specificity compared with a polymer-based commercial benchmark. Compatibility with commercial markers during co-staining was also confirmed. Furthermore, our markers show promising performance for immunophenotyping and potential implementation in CyTOF systems.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metal‐Chelatable Porphyrinic Frameworks for Single‐Cell Multiplexing with Mass Cytometry

Chen

Wang

Wang³

et al. 2022

Angewandte Chemie

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“…Winnik and co-workers recently reported dipicolylamine based mass cytometry tags that bound to soft metals, such as rhenium and platinum, instead of rare earth metals, and subsequently, employed thiol-maleimide or DBCO-azide reactions to conjugate antibodies for cellular profiling. 156 Inductively coupled plasma mass spectrometry (ICP-MS) can subsequently resolve and quantify metal tags internalized by target cells. Although mass cytometry offers a rapid and parallelized way (Figure 7) to measure perturbations in cellular states induced by small molecule drug libraries, 157 it is yet to be adopted for polymeric gene delivery.…”

Section: High-throughput Evaluation Of Polymeric Gene Delivery In Cel...mentioning

confidence: 99%

“…While fluorescence-based techniques such as microscopy and flow cytometry are limited by the number of channels that can be measured simultaneously, mass cytometry reduces interchannel overlap, as well as autofluorescence, enabling multiplexed analytical schemes and boosting sample throughput. − In this technique, heavy metal isotopes can be chelated to polymeric vehicles, − allowing us to label polyplexes using metal tags that vary in their mass to charge ratio. Winnik and co-workers recently reported dipicolylamine based mass cytometry tags that bound to soft metals, such as rhenium and platinum, instead of rare earth metals, and subsequently, employed thiol-maleimide or DBCO-azide reactions to conjugate antibodies for cellular profiling . Inductively coupled plasma mass spectrometry (ICP-MS) can subsequently resolve and quantify metal tags internalized by target cells.…”

Section: High-throughput Evaluation Of Polymeric Gene Delivery In Cel...mentioning

confidence: 99%

Materiomically Designed Polymeric Vehicles for Nucleic Acids: Quo Vadis?

Kumar

2022

ACS Appl. Bio Mater.

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Despite rapid advances in molecular biology, particularly in site-specific genome editing technologies, such as CRISPR/Cas9 and base editing, financial and logistical challenges hinder a broad population from accessing and benefiting from gene therapy. To improve the affordability and scalability of gene therapy, we need to deploy chemically defined, economical, and scalable materials, such as synthetic polymers. For polymers to deliver nucleic acids efficaciously to targeted cells, they must optimally combine design attributes, such as architecture, length, composition, spatial distribution of monomers, basicity, hydrophilic−hydrophobic phase balance, or protonation degree. Designing polymeric vectors for specific nucleic acid payloads is a multivariate optimization problem wherein even minuscule deviations from the optimum are poorly tolerated. To explore the multivariate polymer design space rapidly, efficiently, and fruitfully, we must integrate parallelized polymer synthesis, high-throughput biological screening, and statistical modeling. Although materiomics approaches promise to streamline polymeric vector development, several methodological ambiguities must be resolved. For instance, establishing a flexible polymer ontology that accommodates recent synthetic advances, enforcing uniform polymer characterization and data reporting standards, and implementing multiplexed in vitro and in vivo screening studies require considerable planning, coordination, and effort. This contribution will acquaint readers with the challenges associated with materiomics approaches to polymeric gene delivery and offers guidelines for overcoming these challenges. Here, we summarize recent developments in combinatorial polymer synthesis, high-throughput screening of polymeric vectors, omics-based approaches to polymer design, barcoding schemes for pooled in vitro and in vivo screening, and identify materiomics-inspired research directions that will realize the long-unfulfilled clinical potential of polymeric carriers in gene therapy.

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Metal‐Chelatable Porphyrinic Frameworks for Single‐Cell Multiplexing with Mass Cytometry

Chen

Wang

Wang³

et al. 2022

Angew Chem Int Ed

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Single‐cell multiplexing is key to exploration of the heterogeneous cell populations in biological systems. Although the state‐of‐the‐art mass cytometry (CyTOF) possesses high resolution and multiple dimensions, the lack of suitable marker materials prohibits fully exploiting the available CyTOF detection channels. Here we report a new design strategy for CyTOF markers using functionalized mesoporous porphyrinic frameworks (MPFs) as scaffolds for chelating metals that have been unachievable by conventional approaches. We developed surface modification for stably dispersing the MPF nanoparticles (<40 nm) during the metalation and antibody conjugation processes. Our markers exhibit higher sensitivity and comparable specificity compared with a polymer‐based commercial benchmark. Compatibility with commercial markers during co‐staining was also confirmed. Furthermore, our markers show promising performance for immunophenotyping and potential implementation in CyTOF systems.

show abstract

Polymeric dipicolylamine based mass tags for mass cytometry

Abstract: Mass cytometry is an emerging powerful bioanalytical technique for high-dimensional single-cell analysis. In this technique, cells are stained with metal-isotope-tagged antibodies and are analyzed by an inductively coupled plasma time-of-flight...

Cited by 13 publications

References 49 publications

Metal‐Chelatable Porphyrinic Frameworks for Single‐Cell Multiplexing with Mass Cytometry

Metal‐Chelatable Porphyrinic Frameworks for Single‐Cell Multiplexing with Mass Cytometry

Materiomically Designed Polymeric Vehicles for Nucleic Acids: Quo Vadis?

Metal‐Chelatable Porphyrinic Frameworks for Single‐Cell Multiplexing with Mass Cytometry

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