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Related Experiment Video

Updated: Sep 4, 2025

Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody

Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody

Published on: May 16, 2020

Tumor-Associated Enzyme-Activatable Spherical Nucleic Acids.

Wuliang Zhang^1,2, Cassandra E Callmann^1,2, Brian Meckes^1,2

¹Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.

|July 18, 2022

Summary

This summary is machine-generated.

Researchers developed peptide-based, tumor-responsive coatings for nanomaterials. This strategy enhances tumor targeting, extends blood circulation, and reduces immune responses for effective nanomedicine delivery.

Keywords:

PEGylation immunogenicity matrix metalloproteinase-cleavable spherical nucleic acids tumor accumulation zwitterionic peptides

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Area of Science:

Nanomedicine
Biomaterials Science
Drug Delivery Systems

Background:

Systemic nanomedicine faces challenges in achieving efficient tissue targeting, avoiding rapid clearance, and minimizing immunogenicity.
Current strategies often struggle to balance these competing requirements for effective *in vivo* applications.

Purpose of the Study:

To develop a generalizable strategy for enhancing nanomaterial tumor accumulation, prolonging blood circulation, and limiting immune activation.
To investigate the efficacy of peptide-based, tumor-responsive, 'sheddable' coatings for spherical nucleic acids (SNAs).

Main Methods:

Synthesized SNAs with exterior coatings of zwitterionic polypeptides containing recognition sequences for tumor-associated proteases.
Evaluated the cleavage of the polypeptide coating by matrix metalloproteinases (MMPs) *in vitro* and *in vivo*.
Compared the tumor accumulation, blood circulation time, and cellular uptake of coated SNAs against controls.

Main Results:

The peptide-based coating was rapidly cleaved by MMPs, leading to increased SNA cellular uptake.
The zwitterionic nature of the coating shielded SNAs from immune recognition, extending circulation time.
Coated SNAs demonstrated improved tumor accumulation and *in vivo* cellular uptake compared to uncoated controls.

Conclusions:

Peptide-based, tumor-responsive, sheddable coatings offer a viable strategy to enhance nanoparticle tumor accumulation.
This approach effectively improves systemic delivery of nanomaterials with reduced immunogenicity.
The strategy holds promise for the *in vivo* delivery of oligonucleotides and other nanomedicines.