The Technology
Sono-dynamic therapy (SDT) is anti-cancer therapy that utilizes deep tissue-penetrating therapeutic ultrasound (US) waves to activate a sonosensitizer, thereby locally generating reactive oxygen species (ROS) in the tumor microenvironment and triggering cancer cell apoptosis. SDT is localized and minimizes side effects in off-target body sites. Usually, sonosensitizers are organic molecules that undergo biodistribution based on physicochemical properties such as any drug, and with limited targeting to the tumor. Nanoparticulate sonosensitizers that accumulate in the tumor according to their size are under preclinical investigation with limited success due to the inability to actively target cancer cells. We developed a novel family of hybrid nanomaterials composed of amorphous titanium dioxide (aTiO2) and amphiphilic poly(ethylene)-b-poly(propylene) block copolymers (PEO-PPO) with fine-tunable size between 30 and 350 nm and surface properties for actively targeted SDT of solid tumors. The aTiO2 matrix is an efficient sonosensitizer, while the PEO-PPO copolymer confers surface PEGylation. In addition, a plethora of targeting ligands (sugars, peptides) can be conjugated to the block copolymer to produce hybrid nanoparticles with a modified surface that actively target receptors/transporters overexpressed in specific cancers. Hydrophobic PPO blocks in the block copolymer also enable the encapsulation of hydrophobic anti-cancer cargos for combination therapies. Our hybrid nano-sonosensitizers pave the way for the personalization of cancer treatments based on the solid tumor features and microenvironment (e.g., vascularization, parenchyma) to maximize accumulation and efficacy. We have demonstrated the feasibility of our novel nanotechnology for the precise and efficacious actively targeted SDT of a sarcoma overexpressing glucose transporter using glucosylated hybrid aTiO2/PEO-PPO nanomaterials initially in 2D and 3D cancer cell cultures in vitro and then, in a murine subcutaneous model in vivo with outstanding results (see exemplary figures).
Advantages
- Local, focused cancer treatment
- Deep tissue penetration.
- Simple, reproducible, flexible, and cheap method to synthesize drug-free hybrid sonosensitizer nanoparticles of controlled size.
- Adaptable nanoparticle size between 30 and 350 nm (dynamic light scattering).
- Easy and modular nanoparticle surface modification for active, personalized targeting to tumors.
Applications and Opportunities
- Sono-dynamic cancer therapy
- Targeted drug delivery with combination therapy (SDT + Drug)
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