Achieving targeted intratumoral drug delivery

19 Sep 2025 6min read

Drug treatments serve as a vital line of defense alongside surgery and radiotherapy. They include chemotherapy, hormone therapy, immunotherapy and targeted therapy. Most drug treatments are delivered systemically, circulating through the bloodstream to reach cancer cells. Systemic cancer drug delivery, however, presents challenges such as toxicity, poor tumor penetration and low efficacy, often requiring higher volumes of expensive drugs.

An alternative approach is targeted delivery. This can involve directly administering drugs to the tumor (intratumoral delivery) or developing targeted drug therapies designed to selectively interact with cancer cells, a principle that can also be applied to immunotherapy drugs.

Understanding current drug therapies for cancer treatment

Chemotherapy: Traditional chemotherapy agents inhibit cell proliferation but can affect both cancerous and healthy cells, leading to significant side effects for patients.

Hormonal therapies: These therapies target cancers that are dependent on hormones for growth by modulating hormone production.

Immunotherapy: This enhances or utilizes the body’s immune response to recognize and destroy cancer cells.

Targeted intratumoral drug delivery

Emerging therapies like immune checkpoint inhibitors and CAR-T cells are transforming oncology, but their systemic biodistribution raises safety issues, leading to suboptimal doses or even limiting their clinical development. Intratumoral drug delivery facilitated by advanced drug delivery devices or systems offers an alternative approach by concentrating drugs directly within the tumor, potentially increasing efficacy and reducing side effects by enhancing retention and reducing off-target toxicity.

However, intratumoral delivery comes with different challenges such as poor distribution within the tumor, difficulty with surgical access, reliable dosing and overcoming high tumor density and high interstitial pressure which can impede drug penetration.

Technological innovations are addressing these challenges through a variety of approaches, including optimizing injection techniques, enhancing drug formulations and modifying the tumor microenvironment to improve intratumoral drug delivery for cancer treatment.

Injection techniques

Intratumoral administration can be realized through direct or image-guided injection. Modifications in needle design, such as the use of multi-hole needles and microneedles, have shown advantages, particularly in patients with firm tumors. These modifications help reduce injection pressure and distribute the drug more evenly.

Pressure-enabled drug delivery systems, such as the Pressure-Enabled Drug Delivery™ method from TriSalus Life Sciences, modulate intravascular pressure to enhance regional delivery.

Drug formulation

Suitable drug formulations, such as hydrogels, play a crucial role in improving drug loading and drug release kinetics. Shear-thinning hydrogels, which have tunable viscosities, are particularly suited for intratumoral drug delivery. These materials can flow under shear stress, allowing for easy injection and quickly solidify upon administration, ensuring controlled release of therapeutic agents over time. Similarly, thermosensitive hydrogels, which transition from a liquid state at room temperature to a gel at body temperature, are also being explored to enhance drug retention.

These systems have shown promise in delivering a variety of therapeutic agents, including chemotherapeutics, cytokines and immunotherapy treatments.

Tumor microenvironment

The tumor microenvironment (TME) refers to the surrounding cellular and extracellular components that interact with tumor cells. These can manifest as poor blood supply and increased interstitial fluid pressure or physical barriers that obstruct drug diffusion. The composition and density of these barriers can vary widely within different tumors, affecting how well drugs are delivered. Techniques like external beam radiation and hyperthermia have been shown to reduce tumor interstitial pressure or increase tumor blood flow and vascular permeability, making the tumor more amenable to drug delivery.

Intratumoral drug delivery technology development

Given the heterogeneous nature of tumors and their microenvironments, a personalized approach to drug delivery can be considered. Understanding the biophysical properties of individual tumors, alongside robust simulation models and empirical data, could enable the development of tailored drug administration strategies.

This may involve integrating real-time feedback mechanisms that monitor drug penetration and efficacy. Additionally, techniques such as biopsies and ex vivo characterization of the tumor microenvironment can provide insights into optimizing delivery methods. A recent study has demonstrated the ability to accurately predict the spatial liposome accumulation and interstitial fluid pressure for an individual tumor based on physics-informed machine learning analysis of computed tomography (CT) imaging data.

Furthermore, Optics11Life offers nanoindenters for mechanical characterization that can enable understanding of cancer cell mechanics such as stiffness, elasticity and hardness. These properties often differ significantly from those of healthy cells and can influence tumor behavior, growth and response to treatment. For those developing intratumoral drug delivery devices, having this understanding is important to inform the design of delivery systems that are better adapted to the physical characteristics of the tumor, potentially improving drug penetration and therapeutic efficacy.

A significant challenge in development of intratumoral drug delivery technology is the design of needles capable of delivering viscous formulations, especially in hard-to-reach areas. This could be addressed through robotic systems. A needle designed for precise maneuvers must be flexible enough to navigate challenging angles while being robust enough to penetrate tumor tissue without compromising the drug load.

Further preclinical research is necessary to explore factors influencing intratumoral delivery, such as flow rates, needle design, dosing and formulation characteristics. Conducting ex vivo testing or utilizing intraoperative metrics can significantly aid in formulating individualized intratumoral drug delivery strategies, enhancing the overall effectiveness of cancer treatment.

CT-guided transthoracic fine needle aspiration in a patient with a lung tumor

Intratumoral drug delivery offers a promising alternative to systemic therapies by enhancing local efficacy and reducing side effects. With advances in formulation, drug delivery devices and tumor characterization, this approach is becoming increasingly personalized and precise, paving the way for more effective and safer cancer treatments.

This blog is part of a series on “The future of oncology – medical technologies that are transforming cancer treatment.” Read the blogs on innovations in surgical oncology and radiotherapy ablation technologies for cancer treatment.