Tumor agnostic drug delivery with dynamic nanohydrogels

Area of Science:

• Biotechnology
• Nanomedicine
• Oncology

Background:

• RNA interference (RNAi) offers targeted oncogene regulation but faces significant delivery challenges in cancer therapy.
• Existing RNAi delivery strategies have shown limited clinical translation due to systemic obstructions and poor tumor localization.
• Developing effective and safe delivery systems is crucial for realizing the therapeutic potential of RNAi in oncology.

Purpose of the Study:

• To develop a novel nanohydrogel platform (SANGs) for efficient and selective delivery of RNAi payloads to solid tumors.
• To investigate the tumor-homing, cellular internalization, and payload-agnostic capabilities of the SANGs platform.
• To evaluate the therapeutic efficacy, safety, and underlying delivery mechanism of SANGs in preclinical cancer models.

Main Methods:

• Development of self-agglomerating nanohydrogels (SANGs) capable of carrying multiple RNAi payloads.
• Intravenous administration of SANGs in rodent models of aggressive cancers to assess tumor accumulation and retention.
• Evaluation of oncogene suppression, tumor sensitization to therapy, and safety profiles in simulated clinical applications across multiple species.

Main Results:

• SANGs demonstrated preferential accumulation and durable retention in primary and metastatic tumor sites across four aggressive cancer models.
• The SANGs platform successfully delivered multiple RNAi payloads, leading to significant oncogene expression suppression.
• Treated tumors showed sensitization to therapies, and SANGs exhibited a favorable safety profile in preclinical species, indicating potential for clinical use.

Conclusions:

• The SANGs platform provides an enabling technology for RNAi-based cancer therapeutics, overcoming key delivery barriers.
• Emergent material properties of SANGs facilitate durable solid-tumor delivery without the need for specific targeting ligands.
• SANGs are poised for advanced pharmaceutical development for treating multiple solid-tumor indications.