C'Dots encapsulate a near-infrared dye within a rigid silica shell which enhances its fluorescence. The silica shell is then coated with a layer of polyethylene glycol (PEG) allowing it to be functionalized with a wide variety of targeting ligands, therapeutic payloads and radioactive tracers. Due to their small size, C’Dots are rapidly eliminated from the circulation primarily through the kidneys.
The modular nature of the C-Dot platform is designed to make use of a portfolio of targeting capabilities to enable precision targeting of chosen cancer cells or mutations. A range of imaging and therapeutic payloads can also be attached.
The intrinsic capability of our ultra-small particle platform to target cancer cells, or clear safely from the body primarily via the renal system offers game-changing potential across the diagnosis and treatment of solid primary tumor and metastatic cancers.
a. Target or Clear™
C’Dot-Drug-Conjugates (CDCs) have an average hydrodynamic diameter around 7 nm (a nanometer is one billionth of a meter, or 10-9 meters). This ultra-small size, combined with favorable surface chemistry properties, enables efficient clearance from the circulation through the kidneys. Following systemic administration, CDC’s target and penetrate tumors, attach to cell surface antigens, and effectively deliver cytotoxic drug payload to the tumor cells. Residual circulating CDC’s are removed from the body through efficient renal clearance, thus reducing non-specific healthy organ accumulation and off-target toxicity.
The Target or Clear™ capability of our platform addresses the major limitations of traditional drug carriers (e.g. small molecular, polymers, liposomes, antibody, etc.) and offers game-changing potential for treating both primary and metastatic cancers.
b. Solid tumor penetration
An increasing number of studies have demonstrated the enhanced solid tumor penetration properties of the C’Dot platform. Conversely, traditional antibody-drug-conjugates (ADC) and liposome-based drug delivery system (DDS) are known for their limitations in solid tumor penetration due to their relatively large platform sizes, e.g. over tens or hundreds of nanometers.
c. Versatile surface chemistry
Elucida’s proprietary surface chemistry technique enables C’Dots’ post-synthesis functionalization with large amounts of toxic payloads, radionuclides, and cancer-targeting ligands. A single C’Dot can carry up to 80 molecules of synthetic drug payload without compromising the desired tumor active targeting and pharmacokinetic properties. In comparison, the optimal drug to antibody ratio (DAR) of traditional Antibody Drug Conjugates is limited to around 4 to 8 drug molecules.
d. Brain tumor targeting
To date, targeted delivery of toxic payloads to solid tumors in the brain has remained a major challenge in the care of patients with primary or metastatic brain tumors. Unlike many conventional targeted delivery platforms, C’Dots have demonstrated the ability to penetrate and distribute in brain tumors in patients (Phase I first-in-human clinical trials) and delivering toxic payloads to brain tumors in pre-clinical studies. This is attributed to their ultrasmall size and unique surface chemistry properties, enabling C’Dots to effectively cross the disrupted blood-brain-barrier (BBB) and diffuse through intratumoral compartments in these often hard to reach tumors.
e. Overcoming cancer heterogeneity
Although conventional antibody-drug-conjugates (ADCs) offer a highly specific targeted drug delivery approach, they are limited in their ability to deliver drug payload to low or non-antigen expressing cells. Considering that most tumors are a heterogeneous collection of tumor cells with variable antigen expression levels, ADC’s are often limited in their cell killing capacity. C’Dots differ from ADCs in that they can be taken up by tumor cells in both an active and passive process, enabling killing of both high and low antigen expressing cells.
The combination of the unique properties, including tumor penetration, high payload loading capacity, and capability to deliver drugs to low receptor expression cancer cells, endows the C’Dot platform with great potential to overcome tumor heterogeneity, which has been a major challenge for the conventional targeted delivery platforms, e.g. ADCs.