Intraperitoneal Injection of Nanoparticles Results in Near Perfect Localization Within Peritoneal Tumor Deposits

Technology

This invention is a novel nanoparticle that can deliver therapeutics, RNA, and imaging molecules to the intraperitoneal space. The nanoparticles are composed of block copolymers with a hydrophobic core and a hydrophilic corona. Drug and imaging molecules are covalently linked to the hydrophobic core of the nanoparticles, and the hydrophilic arms of the nanoparticle can carry an RNA cargo. As a proof of principle, the inventors used an in vivo mouse transplant model of ovarian cancer to demonstrate effective tumor targeting and dosing. When nanoparticles carrying NIR-II imaging molecules are injected into the IP cavity of tumor-bearing mice the nanoparticles target very specifically to the tumor and facilitate NIR imaging with a high signal to noise ratio. Additionally, the inventors loaded the nanoparticles with platinum-based chemotherapeutic agents and siRNA or CRISPR/Cas9 RNAs against the gene BCL-2, which has a known role in ovarian cancer recurrence. Mice treated with oxaliplatin-BCL-2 conjugated nanoparticles demonstrate striking reductions in tumor size and increased lifespan, even in mice with platinum-resistant tumors. In conclusion, this nanoparticle technology has tremendous potential as both an imaging tool and a drug delivery method for treating IP cancers.

Problems Addressed

The peritoneal cavity is the fluid filled space that surrounds the stomach, intestines, liver, and in women, ovaries. Cancers such as ovarian, colorectal, pancreatic, breast, and cervical cancers can metastasize and form tumors in the intraperitoneal (IP) space. IP metastases have poor prognosis, which is partially due to the lack of effective treatment strategies for IP tumors. Systemic intravenous treatment does not effectively deliver therapeutics to the peritoneum. Delivering drugs directly to the IP cavity can slightly increase efficacy, but most cancer therapeutics are designed for IV delivery and have suboptimal performance when delivered IP. There is therefore a great need for IP optimized drug delivery methods.

Advantages

• Specific and effective targeting of nanoparticles to IP tumors
• Modular design allows delivery of chemotherapeutics, RNAs, and/or imaging molecules
• Compatible with siRNA or CRISPR-Cas9 gene editing
• Therapeutic potential for treating platinum-resistant ovarian cancer
• Compatible with NIR imaging technologies