A major breakthrough in cancer drug delivery took place in 1995, when the FDA approved the first nanodrug, Doxil—a liposomal formulation of doxorubicin engineered to preferentially accumulate in tumors. Since then, the agency has cleared dozens of additional nanoparticle-based cancer therapies.¹ A complementary milestone followed in 2000 with the approval of the first antibody-drug conjugate (ADC), Mylotarg, which used an anti-CD33 antibody to deliver a cytotoxic agent directly to leukemia cells.
These advances have laid the groundwork for a new generation of cancer delivery platforms. What innovations will define the landscape in 2026? To find out, we spoke with four leading companies whose solutions include novel catheter systems, nanotechnologies, and click chemistry approaches.
Introducing click chemistry
Despite the promise of ADCs in recent years, José M. Mejía Oneto, MD, PhD, CEO of Shasqi, notes several limitations.
He explains that ADCs consist of a toxic payload linked directly to a tumor-targeting antibody. However, as these antibodies are eliminated from the body, they are taken up nonspecifically by normal tissues, where they release their active payload. Over 99% of the payload is typically delivered to normal tissues, leading to unwanted toxicity.
“The premise for our company is that we want to separate the targeting process (typically involving an antibody) from the drug release (payload),” notes Travis Biechele, PhD, the head of research. “We call this pre-targeting.”
However, pre-targeting requires a technology that enables the reunion of the target and the toxic payload in the human body. For Shasqi, that technology is click chemistry, the development of which led to the 2022 Nobel Prize in Chemistry.
What is click chemistry? “The easy way to explain it is that you have Compound A and Compound B, which react with each other without disrupting biological processes,” notes Mejía Oneto. “An analogy is two sides of a seatbelt that click together while ignoring everything else in the car.”
“The beauty of click chemistry—which involves a rapid covalent interaction that is highly selective—is that the body can’t see it because it is a piece of chemistry,” he adds. “It does not interfere with any of the body’s natural processes.”
Biechele provides a more detailed description of the company’s Click Activated Protodrugs Against Cancer (CAPAC) platform. Briefly, a binder is first administered, which binds to the tumor antigen. The second step involves administering a payload, which is activated only at the site of the binder. Following the click chemistry reaction at the tumor, the binder activates the highly permeable payload at the cell surface. Finally, the payload permeates the tumor, killing the tumor cells.
“Ultimately, this allows you to activate the payload only at the site of the tumor antigen,” Biechele notes. “Anything that is not captured during the click reaction clears the body rapidly without toxicity.”
Shasqi was the first company to test click chemistry in the human body, with 50 patients tested so far. “It was amazing to confirm that our technology is working inside the human body,” says Mejía Oneto. “When you go into humans, you see the two pieces reacting with each other and releasing an active drug.”
As part of the first-in-human trial, participants received more than 15 times the standard dose of the chemotherapy drug doxorubicin every 21 days for up to one year. “Usually, a patient can only receive seven doses of doxorubicin before they have cardiac issues,” notes Mejía Oneto. “However, we never saw cardiac issues in our trial.”
Mechanical delivery of chemotherapy
Traditional chemotherapy is associated with many inherent limitations, notes Shaun R. Bagai, CEO of RenovoRx. “We generally give a systemic drug that circulates the whole body with the goal of getting some to the tumor,” he says. “However, this causes toxicity, and in many types of tumors, you may not get much drug into the tumor.”
Bagai explains that RenovoRx has developed a device that uses pressure to force drug delivery across the vessel wall near the tumor, bathing the targeted local tumor tissue in a process called trans-arterial micro-perfusion.
Briefly, a catheter (or small plastic tube) is inserted into the leg via a small incision and delivered to an artery adjacent to the tumor. The physician uses imaging guidance to position the device and deliver a full dose of chemotherapy at the tumor site.
“Instead of flooding the whole body with chemotherapy, it’s delivered locally to get high concentrations of the drug into the tumor tissue,” notes Bagai.
Thus far, pancreatic tumors have been a good candidate for RenovoRx’s technology because of their limited blood supply. “With pancreatic cancer—as well as bile duct cancers, glioblastomas, uterine tumors, and some lung cancers—very little of the circulating blood in the body gets into these tumors,” notes Bagai. “This renders them almost chemo-resistant.”
Bagai mentions the company’s Phase III trial for surgically unresectable stage 3 pancreatic cancer, which is nearing completion of enrollment. The trial is comparing systemic chemotherapy (the standard of care) to intra-arterial local delivery of gemcitabine with RenovoRx’s catheter system.
Although patients in the company’s Phase I and II trials had a historical life expectancy of just 12 to 18 months, Bagai highlights that select patients have survived for up to five years.
“We have also seen a massive reduction in systemic exposure to chemotherapy because we are giving the drug locally,” he says. “And while most patients undergoing systemic chemotherapy are very tired and sick, our patients often feel fine almost the next day.”
The device component of the drug-device combination is FDA-cleared, and the company has initiated commercialization. Patients can now receive the treatment, which is broadly indicated for the delivery of any therapy (including chemotherapy) through the peripheral vasculature.
“There are several companies working on Trojan horse-type drugs like nanotherapies or immunotherapies, where they try to mask the drug for better tumor cell uptake,” notes Bagai. “In the future, we see our technology actually delivering many of these new agents that wouldn’t ordinarily find their way into tumor cells.”
Fighting cancer with physics
Laurent Levy, PhD, CEO of Nanobiotix, explains how the company’s engineered nanotherapeutics harness the laws of physics at a subcellular level.
The company’s lead technology—called a nanoradioenhancer—comprises a suspension of crystalline, inorganic nanoparticles that are directly injected into solid tumors. When activated by radiation, the nanoradioenhancer absorbs and releases energy that destroys the tumor from within, without increasing damage to surrounding healthy tissue.
“In simple terms, we make the localized tumor-killing effect of radiotherapy significantly more powerful,” notes Levy. And because the treatment is localized and patient-agnostic, it does not depend on a tumor’s genetic profile or immune status.
Administration via intratumoral injection allows the nanoradioenhancer to integrate seamlessly into existing radiotherapy workflows—without the need for new machines, new specialists, or an added burden on the patient.
The company’s lead investigational nanoradioenhancer, JNJ-1900 (NBTXR3–invented at Nanobiotix and now globally licensed to Johnson & Johnson), is in a pivotal Phase III study for locally advanced head and neck cancer. This trial targets participants who are ineligible for standard-of-care platinum-based chemotherapy and therefore have limited treatment options.
Beyond that, JNJ-1900 is also being investigated across a broad pan-tumor program, including other head and neck cancer indications, non-small cell lung cancers, pancreatic cancer, esophageal cancer, and melanoma. Favorable safety profiles have been observed across all clinical trials conducted to date.
“We believe that we are only scratching the surface of what physics-based nanotherapeutics can do for the treatment of major diseases,” notes Levy. “While biology and chemistry have brought us important advances over the past several decades, physics opens an entirely new dimension—one that can be applied more broadly and more predictably.”
Melting tumors with nanorods
Sona Nanotech is also developing novel nanotherapeutics with special properties near the atomic scale, explains David Regan, CEO.
The company’s gold nanorods are 40–50 nanometers in length, while the aspect ratio (the length-to-width ratio) is engineered to permit these particles to resonate at specific wavelengths.
Sona’s gold nanorods—which are inert, nontoxic, and uniquely biocompatible—are first injected into a solid cancer tumor. Next, the tumor is exposed to near-infrared light, allowing non-thermal light energy to harmlessly penetrate about 2.5 cm of tissue. When tuned to the matching wavelength, the light energy causes the nanorods to resonate, which converts the non-thermal energy into heat.
“The underlying phenomenon here is similar to how a tuning fork works,” notes Regan.
The temperature in the tumor is then maintained between 42°C and 46°C for five minutes. Within this range, cancer cells undergo apoptotic cell death, while healthy cells, which can withstand temperatures up to 52°C, remain unaffected.
Cell death also releases neoantigens—antigens not previously recognized by the immune system—that can prime the immune system to attack the tumor. Notably, this mechanism appears to enhance the effectiveness of immunotherapies such as Keytruda.
The company has just completed its first-in-human feasibility study. Notably, six of ten patients (for whom immunotherapy drugs had been ineffective) experienced a complete clearance of melanoma in the tumor, with no major side effects.
Although this first study was in melanoma patients, preclinical studies suggest that the technology may also be useful for other solid cancer types, including triple-negative breast cancer and colorectal cancer.
“We are also working on advanced concepts to conjugate our gold nanorods to antibodies and drug molecules so that this treatment could be used in a tumor-targeting fashion,” notes Regan.
References
- Pavelić K, Kraljević Pavelić S, Bulog A, et al. Int J Mol Sci. 2023;24(16):12827. doi: 10.3390/ijms241612827.
