# Development of safe and effective immunotherapeutics for treatment of opioid abuse and overdose

> **NIH NIH R43** · VITAN-BIOTECH, LLC · 2020 · $224,940

## Abstract

Project Summary
 The abuse of opioids, which include heroin and synthetic opioids (e.g., fentanyl), is a growing
problem in the United States that is partly responsible for the recently declared National Emergency for
Opioid crisis. Between 2006 and 2015, the number of heroin-related deaths increased over 600% where
heroin laced synthetic opioids (e.g., the “killer opioids”) is responsible most of the deaths from abuse of
opioids. Although FDA-approved medications to treat opioid addiction are available, the utilization rate for
these medications is limited from side effects, tight prescription guidelines, and restricted availability. The
ongoing rise in opioid abuse creates a dire need for new therapy that offers long-lasting, safe, and cost-
effective interventions for overdoses and relapses but avoid side effects associated with current addiction
medications. Immunopharmacotherapy using drug-specific antibodies (i.e., immunoantagonists) to block
opioid drug activity and prevent the target opioids entering the brain are promising treatment approach
that have less side-effect than the traditional drug-based opioid replacement treatment. In this SBIR project,
we propose to develop a new class of immunotherapeutics-the nanobodies (e.g. the single domain
antibodies, sdAbs) that have high specificities and affinities to heroin, fentanyl for the treatment of “killer
opioids” overdose and abuse. We expect the opioid-specific nanobodies will be better
immunotherapeutics than traditional immunoglobulin G-based drug antibodies because nanobodies are
extremely robust, highly resistant to denaturation, have superior tissue penetration, and have ability to cross
blood brain barrier. Our goal is to achieve long-lasting and high titer antibodies to opioid drugs of abuse.
The phase I project will focus on in vitro methodologies for the generation of specific nanobodies with high
affinities to “killer opioids” from phage-display nanobody library. In the Phase I project, we will make
derivatives of opioid drugs such that they can be chemically conjugated at high density on magnetic
beads, and isolate high affinity nanobodies specific to heroin and fentanyl. Furthermore, we will engineer
and express individual single domain antibody to produce bivalent (multivalent) nanobody or multi-
nanobody-conjugated nanoparticles as new therapeutic modalities targeting two or more opioids
simultaneously. These nanobodies will improve upon current drug-specific antibody paradigms by
increasing multivalency and allowing pharmacokinetic customization, while avoiding interactions with
endogenous antibody receptor pathways. Successful completion of Phase I project will generate novel
opioid-specific nanobodies and provide a framework for the development of immunotherapeutics against
other drugs of abuse. In future Phase II, we will perform the pre-clinical in vitro and in vivo rodent
pharmacokinetic study of individual nanobodies and multivalent nanobody for therapeutic neutraliz...

## Key facts

- **NIH application ID:** 10010998
- **Project number:** 1R43DA051296-01
- **Recipient organization:** VITAN-BIOTECH, LLC
- **Principal Investigator:** XICHUN ZHOU
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $224,940
- **Award type:** 1
- **Project period:** 2020-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10010998

## Citation

> US National Institutes of Health, RePORTER application 10010998, Development of safe and effective immunotherapeutics for treatment of opioid abuse and overdose (1R43DA051296-01). Retrieved via AI Analytics 2026-06-05 from https://api.ai-analytics.org/grant/nih/10010998. Licensed CC0.

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