# Improving the in Vivo Delivery and Antitumor Efficacy of Antisense Drugs

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $340,177

## Abstract

Abstract
Nucleotide-based drugs, such as antisense (ASO), represent an essential class of drug types that are
particularly useful for those so-called “undruggable” targets by small molecules and antibodies. However, one
of the biggest hurdles in the translation of ASO drugs is the poor in vivo delivery. Several barriers exist to
prevent ASOs from efficiently reaching their target cells in vivo: rapid renal clearance, nuclease degradation,
unspecific absorption, low efficiency to penetrate across the endothelium and spread in extravascular tissue.
In this proposal, I aim to apply the technologies of peptide targeting and nanomaterial to enhance the delivery
efficiency of ASOs into solid tumors.
 To prevent renal filtration and nuclease degradation, ASOs will be encapsulated within porous silicon
nanoparticles (pSiNPs). pSiNPs are biodegradable and have low or no toxicity in vivo. More importantly,
pSiNPs have likely the highest loading efficiency for ASOs and other oligonucleotides. The most important
goal of our proposal is to help ASOs preferentially accumulate in tumors, and penetrate across tumor vessels
to access to those target cells far away from the circulation. Our tumor-penetrating CendR peptides are one
of the few tools available to achieve this goal. By engaging with certain receptor on the tumor vessels, CendR
peptides activate an active transport process across tumor vessels along with a wide range of cargo types,
including pSiNPs. In the Aim 1, I will synthesize CendR-functionalized, ASO-loaded pSiNPs. Besides
chemical characterization, I will also validate the cell entry and gene-silencing efficacy of this system in vitro.
In the Aim 2, I will evaluate the in vivo toxicity, pharmacokinetics and tissue distribution. In the Aim 3, the
gene modulation and tumor-inhibitory efficacy of CendR-pSiNP-ASO will be determined using animal tumor
models. My proposed studies hold great potential for improving the tumor delivery and antitumor efficacy of
ASOs, and accelerating the transition of prototype ASO drugs into the clinic.

## Key facts

- **NIH application ID:** 10219981
- **Project number:** 5R01CA214550-06
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Hongbo Pang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $340,177
- **Award type:** 5
- **Project period:** 2017-12-29 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219981

## Citation

> US National Institutes of Health, RePORTER application 10219981, Improving the in Vivo Delivery and Antitumor Efficacy of Antisense Drugs (5R01CA214550-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10219981. Licensed CC0.

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