# Tumor-Targeted Chemo-Immunotherapy for Osteosarcoma Metastasis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $359,138

## Abstract

Abstract
The primary objective of this proposal is to develop a non-invasive and effective tumor-targeted chemo-
immunotherapy as a novel combination regimen for treating metastatic osteosarcoma tumors in the lungs. It is
well known that recurrent osteosarcoma almost exclusively metastasizes to the lungs and is resistant to single-
agent and combined chemotherapy. New treatment options such as immunotherapy are urgently needed for
combination with chemotherapy to control and eliminate these tumors. We hypothesize that tumor-targeted
delivery of a combination therapy that includes a chemo-drug (doxorubicin, routinely used in clinic to treat
osteosarcoma) and an immune stimulant (IL-12 protein) will demonstrate an improved anti-tumor efficacy
against metastatic osteosarcoma. To test this hypothesis, we will synthesize a novel tumor-targeted RBC-
membrane-cloaked nanoparticle (ttRBC-NP) delivery system and then test the anti-tumor efficacy of the
doxorubicin(DOX)-loaded ttRBC-NP, denoted ttRBC-NP(DOX), using a spontaneously formed post-surgery
metastatic osteosarcoma mouse lung model. The ttRBC-NP(DOX) will next be combined with tumor-targeted
IL-12 protein therapy, denoted ttIL-12, to examine potential synergistic effects on treating metastatic
osteosarcoma. Furthermore, we will explore the impact of this tumor-targeted chemo-immunotherapy on tumor
microenvironment in order to decipher the underlying mechanism. Overall, two specific aims will be pursued
in this proposal, including: (i) to synthesize ttRBC-NP(DOX) and test its anti-tumor efficacy in combination with
ttIL-12 protein therapy against metastatic osteosarcoma; and (ii) to study the underlying mechanisms by which
the targeted combination therapy boosts anti-tumor efficacy against metastatic osteosarcoma. The success of
this project will provide a new and effective treatment option for metastatic osteosarcoma by combining a novel
nanoparticle-based chemotherapy with a powerful IL-12 protein therapy. This work will also advance the
research of nanotechnology in medicine by developing a unique and robust biomimetic nanoparticle delivery
platform that utilizes natural RBC membranes to coat and thus camouflage synthetic drug nanocarriers to
evade the immune system. This work will also significantly improve the understanding of how combinatorial
chemo-immunotherapy impacts the tumor microenvironment and thus enhances the anti-tumor efficacy.

## Key facts

- **NIH application ID:** 9926814
- **Project number:** 5R01CA200574-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** SHULIN LI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $359,138
- **Award type:** 5
- **Project period:** 2016-06-15 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9926814

## Citation

> US National Institutes of Health, RePORTER application 9926814, Tumor-Targeted Chemo-Immunotherapy for Osteosarcoma Metastasis (5R01CA200574-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9926814. Licensed CC0.

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