Carbona Medical Files IPO Prospectus: Pioneering Tumor-Specific Carbon Quantum Dots for Targeted Drug Delivery and Intraoperative Navigation

In October 2023, the Nobel Prize in Chemistry was awarded to Moungi G. Bawendi, Louis E. Brus, and Alexei I. Ekimov for their “discovery and synthesis of quantum dots, laying important seeds for nanotechnology.” When materials enter the nanoscale range, they exhibit properties such as quantum size effects, small-size effects, surface effects, and quantum tunneling effects, thereby displaying physicochemical properties that are markedly different from those of ordinary bulk materials.

Quantum Dots (QDs), also known as semiconductor nanocrystals, are ultra-small nanomaterials. As Johan Åqvist, Chair of the Nobel Committee for Chemistry, stated, “Quantum dots have many fascinating and unusual properties. Most importantly, their color depends on their size.” The emergence of quantum dots offers a novel approach to modulating and tailoring material properties, opening up endless possibilities for the broader application of nanotechnology.

Since 1998, quantum dot technology has been first applied in life sciences as biological fluorescent labels.For instance, quantum dots can be conjugated with biochemical molecules to map cells and organs; their potential utility in tracking tumor tissues in vivo is being investigated; and they are applied in surgical resection of tumor tissues, among other uses. However, quantum dots have long been composed primarily of heavy metals. Despite their excellent performance and wide application in fields such as bioimaging and energy conversion, heavy metal elements can cause environmental pollution and adversely affect biological health, thereby limiting their medical applications within the human body.

Beijing Carbon Medical Technology Co., Ltd. (hereinafter referred to as “Carbon Medical”), established in 2019, has independently developed carbon quantum dots (CQDs), a novel class of nanomaterials with tumor specificity that were synthesized for the first time worldwide.This novel nanomaterial holds promise for revolutionizing targeted cancer therapy and precision diagnostics.Recently, VCBeat interviewed Dr. Ouyang Zhaohuai, Founder and CEO of Carbon Medical.

Ouyang Zhaohuai, Founder and CEO of Carbon Medical, holds a Ph.D. from the United States and is a Professor-level Senior Engineer. He has 30 years of experience in drug R&D and management in both China and the United States. He previously served as Vice President of Beijing Inmei Future Biopharmaceutical Technology Co., Ltd., and as Vice President and Chief Scientist of Beijing BioCapital Crystal Diagnostics Biotechnology Co., Ltd.

As drug carriers, nanomaterials exhibit size-dependent effects based on their nanostructures, which can enhance the efficacy and safety of drugs, improve administration routes, and offer potential solutions for the targeted delivery of anticancer agents.CQDs refer to a novel class of fluorescent carbon nanomaterials primarily composed of carbon, with particle sizes less than 10 nm and possessing either a graphitic crystal structure or a diamond-like structure.

The targeting of nanocarrier drug delivery systems encompasses two mechanisms: passive targeting and active targeting. Due to the intrinsic properties of the materials, nearly all nanocarrier drug delivery systems exhibit passive targeting capabilities. The vascular walls in normal tissues have small intercellular gaps and maintain structural integrity. In contrast, tumor tissues are characterized by abundant vasculature, larger vascular wall gaps, and compromised structural integrity. Consequently, nanomaterials with appropriate dimensions can selectively accumulate in tumor tissues via the Enhanced Permeability and Retention (EPR) effect, thereby achieving passive targeting.

“However, there are differences in the gaps between vascular walls among different tumors, and passive targeting is not universally applicable and has low efficiency. Clinical results have shown that most nanodrugs based on the EPR effect accumulate in organs such as the liver, spleen, and bone marrow, making it difficult to achieve precise tumor targeting,” Ouyang Zhaohuai mentioned. “Active targeting of existing nano-delivery systems is achieved by coupling specific ligands or antibody components with cell surface-specific receptors. This binding can significantly improve drug efficacy, enhance the killing power against tumors, and reduce side effects. However, this active targeting also has some limitations, such as limited target receptors, difficulty in finding pan-cancer targets, and challenges in process and quality control.”

Therefore, the search for nanomaterials with inherent active tumor-targeting capabilities has become an urgent and top priority.

Compared with normal cells, cancer cells require abundant nutrients to meet the demands of their rapid proliferation; therefore, the L-type amino acid transporter LAT1 is overexpressed in a variety of tumor cells or tissues.Leveraging this property, the CQDs independently developed by Carbon Medical feature a structure analogous to large amino acids, enabling them to bind to LAT1 overexpressed in tumor cells. This allows for broad-spectrum, precise, and active targeting of tumor cells, regardless of their origin, location, or type.

Importantly, CQDs can be loaded with various anticancer drugs while retaining their specific tumor-targeting capability. This targeting ability has been observed in experiments involving more than 40 types of tumor cells and over six animal models.

Selective enrichment of CQDs in mice, image provided by the interviewee

This unique CQD material was developed in the laboratory of Professor Fan Louzhen at Beijing Normal University. Building on nearly three decades of accumulated expertise in nanomaterials research, she was the first to discover that this novel class of CQDs exhibits specificity toward a wide variety of tumor cells. Subsequent animal studies and mechanistic validations have consistently demonstrated clear active targeting effects.

Compared with traditional semiconductor quantum dots, carbon quantum dots (CQDs) not only inherit superior optical properties but also address their shortcomings in terms of cytotoxicity and environmental and biological hazards. Furthermore, CQDs exhibit favorable characteristics such as good water solubility, chemical stability, low cost, ease of surface functionalization, and scalability for mass production.

With the publication of research findings and the filing of PCT international patent applications, Professor Fan Louzhen discussed this clinically significant R&D achievement with her college classmate Ouyang Zhaohuai, who brings 30 years of experience in biomedical R&D and management across China and the United States (formerly Vice President and Chief Scientist at Beijing BioCapital Crystal Diagnostics Co., Ltd., and Vice President at Inmi Future). After conducting in-depth evaluations of the project and its industrial potential, the two found common ground and co-founded Carbon Medical, embarking on their entrepreneurial journey.

To date, Carbon Medical has built a research and development as well as industrial team with specialized expertise, extensive professional experience, and a global perspective. The company has also appointed Mike Shepard, one of the inventors of Herceptin—the first monoclonal antibody targeting HER2-positive breast cancer—and winner of the 2019 Lasker Award, as its Chief Medical Officer (CMO).

At the therapeutic end, the broad-spectrum tumor affinity and active targeting capabilities of CQDs can be leveraged to develop a drug delivery system with the characteristics of a universal platform. “As a platform technology, CQD-based nanodelivery offers immense potential. It enables the conversion of conventional non-targeted drugs into cancer-targeted therapies, thereby achieving highly efficient delivery and improved therapeutic efficacy.”Compared with currently marketed nanodelivery systems, carbon quantum dots (CQDs) exhibit superior, label-free active targeting effects and can be applied to various cancer therapies, including chemotherapy, biotherapy, radiotherapy (PET, neutron), phototherapy, and immunotherapy.”

Taking doxorubicin, the most widely used chemotherapy drug in malignant tumor treatment, as an example, it demonstrates significant efficacy in clinical applications for gynecological tumors, liver cancer, lung cancer, breast cancer, lymphoma, multiple myeloma, and head and neck tumors. However, doxorubicin is associated with severe adverse reactions; while killing tumor cells, it also damages healthy cells, leading to side effects such as cardiotoxicity and hair loss, which seriously impair patients' quality of life and survival.

“Existing nanomedicines (such as liposomes) alter drug metabolic pathways and tissue distribution during delivery, thereby reducing damage to normal tissues. However, they can only achieve a limited degree of toxicity reduction and efficacy enhancement. Due to their active targeting capability, carbon quantum dots (CQDs) can effectively deliver drugs specifically to tumor cells, thus reducing systemic side effects, increasing the maximum tolerated dose, and significantly improving therapeutic outcomes.”

Furthermore, CQD-based drug delivery systems exhibit in vivo stability and enable controlled release under appropriate conditions. CQDs can improve drug water solubility, offer flexible administration routes, and provide ease of operation and control. Currently,CQDs can bind covalently or non-covalently with various drugs; more than 20 small-molecule chemotherapeutic agents, including doxorubicin, and siRNA nucleic acid molecules have been tested. CQDs, either alone or in drug-conjugated form, can cross the blood–brain barrier and target intracranial tumors.

Ouyang Zhaohuai introduced, “Compared with the existing nanodelivery systems currently on the market, our CQDs do not require conjugation with tumor-recognizing ligands; instead, they rely on the inherent active targeting capability of the material itself to specifically recognize and enter tumor cells.”This enables Carbon Medical to adopt simpler processes and production methods, facilitating easier mass production and industrialization of its products. Our laboratory has already achieved scale-up of CQDs from the milligram to gram level, and scaling up to kilogram-level mass production is not an issue.”

In diagnostic applications, as a novel class of fluorescent labeling materials, carbon quantum dots (CQDs) offer unique advantages for long-term monitoring of biological activities and in vivo tracing.Compared with traditional organic fluorescent reagents, the emission intensity of CQDs fluorescence is 20 times stronger than that of organic fluorescent dyes, and their stability is more than 100 times higher.. Furthermore, it boasts numerous advantages, including a broad excitation spectrum, narrow emission spectrum, resistance to photobleaching, high photochemical stability, and resistance to decomposition, making it primarily suitable for real-time dynamic fluorescence observation and imaging in living cells.

Surgical resection is typically the preferred treatment for solid tumors, and the ability to achieve complete tumor removal significantly impacts patients’ postoperative survival and quality of life. Although various methods are currently available for tumor diagnosis and preoperative planning, there is still no effective means to provide real-time assistance in determining tumor margins due to limitations in equipment and other factors. Consequently, the assessment of complete resection relies primarily on the surgeon’s experience, posing a risk of positive surgical margins.

Intraoperative imaging agent technology provides surgeons with real-time guidance, facilitating visualization and further improving surgical success rates for patients, thus holding immense potential in a vast blue-ocean market. In November 2021, Cytalux, the world’s first near-tumor-targeted fluorescent imaging agent, received FDA approval for marketing. Cytalux is a near-infrared tumor-targeted contrast agent that targets folate receptors and has currently obtained New Drug Application (NDA) approvals for ovarian cancer and lung cancer.

Unlike Cytalux, which targets the folate receptor, the carbon quantum dots (CQDs) developed by Carbon Medical exhibit broad-spectrum tumor specificity and can be applied to intraoperative imaging for all solid tumors. Furthermore, owing to their optical properties, CQDs generate more stable, durable, and intense fluorescent signals. Consequently, CQD-based intraoperative navigation products will significantly surpass currently marketed alternatives in both versatility and performance.

Currently, Carbon Medical has secured multiple licensing collaborations for the application of CQDs in the field of in vitro diagnostics. The company will next fully advance the preclinical development of its first pipeline involving CQD-mediated delivery of chemotherapeutic agents and its intraoperative imaging pipeline.Ouyang Zhaohuai stated, “Carbon Medical is committed to building CQDs into the world’s unique platform for developing cancer-targeted drugs. We are pioneering unprecedented targeted nano-drugs for cancer therapy based on CQDs, while also licensing our technology to pharmaceutical companies to provide our partners with innovative and disruptive solutions and support.”

From the first application of quantum dot technology as biological fluorescent labels in life sciences in 1998, to the initial report of carbon dots (including carbon quantum dots, CQDs) in 2004, and their subsequent adoption in point-of-care testing (POCT) and biosensing, to today’s applications in intraoperative diagnosis and drug delivery, the trajectory of quantum dot technology illustrates the exploratory journey of a novel medical material driven by cutting-edge scientific research.

Certainly, foundational innovations often face more diverse competition—mass production implementation, process iteration, cost competition, translation of scientific research achievements, recognition from the industrial and industrial ends, and challenges in regulation and approval. Ouyang Zhaohuai mentioned, "The use of quantum dots themselves for drug delivery and therapeutic applications is indeed new. However, their essence remains that of a nanomaterial, and the approval can apply to the review standards for nano-drugs."

In 2021, the CDE issued the Technical Guidelines for Quality Control Research on Nanomedicines (Trial), the Technical Guidelines for Nonclinical Pharmacokinetic Studies of Nanomedicines (Trial), and the Technical Guidelines for Nonclinical Safety Evaluation of Nanomedicines (Trial).

“At the conclusion of the interview, Ouyang Zhaohuai noted that the safety and efficacy of carbon quantum dots (CQDs) have been well validated in small-animal studies conducted by Carbon Medical, and discussions with pharmaceutical companies regarding collaboration are underway. ‘We seek comprehensive support to systematically advance large-animal studies and secure Investigational New Drug (IND) approval as early as possible. This would represent a significant milestone for the entire CQDs platform, enhancing its recognition and paving the way for major collaborations and validation efforts, thereby accelerating our path toward commercialization.’”

For “First-in-class” new materials, their application value, utility, and platform potential require continuous exploration and discovery. Risks and opportunities coexist, and ultimately, the market and users will pay for the value delivered. However, before that happens, we must first ensure that source innovation survives the winter.