# Mechanism of Intratumoral Transport of Particulate Drugs

> **NIH NIH R01** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2021 · $463,570

## Abstract

The tumor vasculature is generally considered as leaky, and thus allows accumulation of big molecules and
particles within a certain size range to penetrate and retain. Consequently, many cancer drugs have been
packaged into simple nanoparticles or composite drug particles in order to improve accumulation in the tumor
tissue and reduce toxicity to the normal organs. Yet there are multiple biological barriers that the particulate
drugs will encounter en route to the tumor such as the myeloid cells with a high phagocytic potential for the
drug particles in circulation and in organs of the mononuclear phagocyte system. In addition, the dense tumor
tissue is filled with extracellular matrix and tumor-associated myeloid cells. It is unclear how the particulate
drugs escape entrapment by the phagocytic cells at the system level and, for the particles that have arrived to
the tumor tissue, how they penetrate the multiple biological barriers inside the tumor and reach the cancer cells.
In this study, we will package doxorubicin in liposomes, micelles and composite particles, and apply them as
model drugs to study the mechanism of intratumoral transport of particulate drugs. We hypothesize that
myeloid cell-mediated transport is an important route of tumor entry and intratumoral distribution of the
particulate drugs. The overall study is divided into three specific aims. In the Aim 1 study, we will examine cell-
mediate tumor entry of particulate drugs. In the Aim 2 study, we will analyze the process of intratumoral
passage of drug particles. In the Aim 3 study, we will investigate potential impact on tumor microenvironment
and anti-tumor immunity as a result of effective intratumoral transport of particulate drugs. Knowledge
generated from this study will provide guidance on design and development of future particulate cancer drugs
with better therapeutic efficacy and low-to-no side effects.

## Key facts

- **NIH application ID:** 10053718
- **Project number:** 5R01CA222959-03
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** Haifa Shen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $463,570
- **Award type:** 5
- **Project period:** 2018-06-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053718

## Citation

> US National Institutes of Health, RePORTER application 10053718, Mechanism of Intratumoral Transport of Particulate Drugs (5R01CA222959-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10053718. Licensed CC0.

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