# Aptamer-Modified POSH Inhibitor Micelles as a Novel Leukemia Treatment Modality

> **NIH NIH R21** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $297,345

## Abstract

According to the American Cancer Society, approximately 25,000 people will die from leukemia this year. Despite
numerous treatment advances, patients with acute lymphoblastic leukemia (ALL) continue to be high-risk and
have a poor prognostic outlook. While some novel therapeutic modalities are being implemented, drug
resistance, cancer relapse, and off-target toxicity indicate a considerable clinical need still exists meaning safer,
more efficient treatment systems must be developed. This collaborative work brings together expertise from the
fields of chemical engineering, materials science, molecular biology, immunology, and clinical medicine to
provide a unique approach to this difficult problem. Preliminary data provides considerable evidence that
inhibition of the Plenty of SH3 Domains (POSH) scaffold complex leads to a blockade in proliferation and/or an
induction in significant apoptosis in the vast majority (15 of 16) of T cell and B cell leukemias evaluated to date.
While promising, the POSH inhibitor peptide therapeutic (POSHINHIB) is not readily internalized and does not
specifically target lymphocytes, both of which greatly limit its bioactivity. We hypothesize that by combining cell-
targeting aptamers (Apts), cell penetrating peptides (CPPs), and peptide amphiphile micelles (PAMs), a novel
biomaterial can be created capable of treating T cell and B cell leukemia. This hypothesis will be tested in Specific
Aim 1 by the synthesis and characterization of Apt-conjugated and CPP-modified POSHINHIB amphiphile micelles
(Apt~A/Tat-POSHINHIBAMs). In Specific Aim 2, Apt~A/Tat-POSHINHIBAM function and specificity for the in vitro
treatment of T cell and B cell ALL that do not respond well to conventional cancer therapeutics will be assessed.
Specific Aim 3 will consist of preliminary experiments designed to evaluate the in vivo antineoplastic effects of
Apt~A/Tat-POSHINHIBAM against human leukemia in a murine xenograft model. This work is expected to provide
a deeper understanding into how directed delivery and biomaterials structure influence the biological efficacy of
therapeutic peptides. While high risk, preliminary data support the substantial therapeutic potential of Tat-
POSHINHIB, show our capacity to fabricate POSHINHIBAMs, and demonstrate Apt~A/PAMs possess enhanced
selective targeting. The proposed research plan will build on these initial results to create a complex delivery
device capable of becoming a clinically applicable treatment. In addition, the modular nature of the nanoparticle
therapeutics developed in this research all them to serve as a platform technology that can be leveraged for the
treatment of other cancers as well as autoimmune diseases.

## Key facts

- **NIH application ID:** 10022329
- **Project number:** 5R21EB026560-02
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** MARK A. DANIELS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $297,345
- **Award type:** 5
- **Project period:** 2019-09-23 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022329

## Citation

> US National Institutes of Health, RePORTER application 10022329, Aptamer-Modified POSH Inhibitor Micelles as a Novel Leukemia Treatment Modality (5R21EB026560-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10022329. Licensed CC0.

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