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“Advanced, Multifunctional Imaging and Therapy of Lymphoma by Molecularly Tailored
Nanoparticles”
We have rationally designed and created a tunable, synthetic delivery platform that is based on
cyclodextrin-containing polymers (CDPs). When combined with therapeutic and imaging agents, the
polymer delivery platform creates multifunctional nanoparticles. Through experimentation, we have
demonstrated that targeted particles of 50 nm in diameter are the most appropriate for systemic use.
These nanoparticles show excellent systemic biocompatibility and efficacious anti-tumor behavior
when carrying either small molecule chemotherapeutic agents or short interfering RNAs (siRNA) and
administered intravenous in rodent models. One variant of this platform is schedule to begin human
clinical trials this year. Here, we propose efforts that involve research groups at Caltech where the
polymer platform was invented and the Lymphoma Specialized Program of Research Excellence
(SPORE) at the City of Hope to develop an effective nanotechnology platform for the systemic
imaging and treatment of lymphoma.
We propose to evaluate the hypothesis that properly designed and engineered, synthetic
CDP-based nanoparticles that are ca. 50 nm in diameter can effectively provide targeted therapeutics
and imaging agents for lymphoma.
Specific Aims:
1.
2.
3.
4.
Create targeted nanoparticles ca. 50 nm diameter for the effective MRI imaging of
lymphoma that have sizes and surface properties (including surface presentation of
protein targeting ligands) that are analogous to those used with the targeted
therapeutics so that the imaging and therapeutic agents have the same biodistribution in
mammals.
Create targeted nanoparticles with the same surface properties as those prepared in
Specific Aim 1 that also contain payloads that are able to provide intracellular,
molecular-level readouts of therapeutic targets.
Create targeted nanoparticles of ca. 50 nm diameter using CDPs with small molecule
chemotherapeutic agents and protein targeting ligands, and test their ability to target
and treat lymphoma in rodent animal models.
Create targeted nanoparticles of ca. 50 nm diameter using CDPs with siRNAs and
protein targeting ligands, and test their ability to target and treat lymphoma in rodent
animal models.
Significance:
The development of an effective, targeted, synthetic platform for imaging and treating patients
in a systemic manner would provide new therapeutic methods for treating lymphoma and metastatic
cancer in general.
Long-term Goals:
The potential for providing new disease treatments for metastatic cancer has been restricted
by limitations in the safe and effective delivery of therapeutic agents. The long-term objective of our
work is to design and engineer a generalized, synthetic platform for ultimately providing targeted
therapies for metastatic cancer. While lymphoma is used here as the cancer type for proof of concept
experiments, the concepts investigated and anticipated outcomes will be readily generalizable to
other forms of cancer.