# Organic nanoparticles for dual MRI-guided therapeutic selection and ovarian cancer drug delivery

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $509,485

## Abstract

Though combinations of cytotoxic drugs are routinely administered to cancer patients in the clinic, nanoparticle
(NP)-based combination therapy still represents an emerging frontier in cancer drug delivery. Effective
combination therapies are particularly necessary for ovarian cancer, as ovarian cancer cells often display
resistance to current clinical therapies such as platinum agents (cisplatin), paclitaxel, and PARP inhibitors
(PARPi), and systemic administration of these drugs in free from is precluded by extreme toxicity. Furthermore,
platinum and PARPi resistance is a major challenge in ovarian cancer therapy. NPs have the potential to
reduce the toxicity of chemotherapy, and they could maximize efficacy and overcome resistance through
rational drug choices that target several disparate DNA repair pathways simultaneously. In order to determine
if a particular drug combination is working, microenvironment-responsive imaging strategies that are clinically
translatable (e.g., MRI) are critically needed. The PI’s group has developed novel organic polymer NPs with
demonstrated advantages in combination ovarian cancer therapy as well as MRI. These studies inspired our
proposed NPs, which combine responsive organic MRI handles and rational drug combinations for image-
guided selection of optimal therapies for ovarian cancer. The proposed research combines a novel drug-NP
and imaging agent synthesis (from Johnson and Rajca) with clinical expertise in ovarian cancer
(Ghoroghchian) and biomedical imaging (Jasanoff) and fundamental cancer biology and targeting (Kufe lab) to
address chemoresistance in ovarian cancer through novel image-guided NP-based combination therapies. The
proposed research will create a new paradigm for ovarian cancer therapy, whereby combinations of several
therapeutic agents are packaged within the same non-toxic carrier and delivered selectively to tumors and MRI
contrast agents within the nanomaterial report on the success of the therapy, thus allowing one to select an
optimum drug combination and ratio for personalized therapy.
HYPOTHESIS: Simultaneous incorporation of multiple small-molecule therapeutic agents and responsive
imaging tags (MRI) into multi-drug-conjugated NPs will lead to novel therapies for ovarian cancer that delay the
development of acquired therapeutic resistance and provide for MRI-guided drug selection. In combination with
other established and experimental agents, one or more NPs will be established with improved activity in
platinum-resistant disease. The already proven safety, pharmacokinetics, biodistribution, and efficacy of 3-drug
containing NPs for high-grade serous ovarian cancer therapy will translate to novel drug combinations that are
effective in vivo, as will be demonstrated by activity in orthotopic patient-derived xenograft models of Pt- and
PARPi-resistant ovarian cancer. Inclusion of multiple drugs in one NP will lead to increased efficacy and
decreased toxicity compared to mixtures of ...

## Key facts

- **NIH application ID:** 9984308
- **Project number:** 5R01CA220468-04
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Jeremiah Allen Johnson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $509,485
- **Award type:** 5
- **Project period:** 2017-09-13 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984308

## Citation

> US National Institutes of Health, RePORTER application 9984308, Organic nanoparticles for dual MRI-guided therapeutic selection and ovarian cancer drug delivery (5R01CA220468-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984308. Licensed CC0.

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