Cancer immunotherapy has emerged as an effective strategy in oncology treatment. However, achieving localized, persistent immune stimulation at tumor sites while effectively counteracting the immunosuppressive tumor environment remains a critical challenge for scientists. Recently, a research team from Zhejiang University (Biomaterials, Volume 312, January 2025, 122751) made a landmark discovery by developing a nanomedicine delivery system based on natural mussel adhesive proteins (NMPs). Utilizing the FluidFM OMNIUM platform, the team precisely measured the adhesion forces between nanomedicines and cells, opening new opportunities for durable immunotherapy.

The graphical abstract published with the paper illustrates how mussel protein-based nanoparticles target tumors, deliver drugs, and activate immune responses through localized photothermal therapy and immunotherapy. The image is freely available for download.

1. Biomimetic Adhesive Proteins Enable Intelligent Drug Delivery System

To achieve targeted and durable cancer immunotherapy, Zhejiang University scientists engineered a nanomedicine system inspired by the strong adhesive proteins of marine mussels. These NMPs, rich in Dopa residues, enable the nanomedicine to adhere at the tumor site for optimal action.

By assembling immunoadjuvant prodrugs and photosensitizers within the NMPs, the team created a co-delivery system for precise, controlled release. When exposed to near-infrared light, the photosensitizer triggers localized photothermal effects that induce immunogenic cell death (ICD)—not only eliminating tumor cells, but also releasing tumor antigens and damage-associated molecular patterns (DAMPs) that activate and amplify anti-tumor immunity.

2. Regulating the Immune Microenvironment: FluidFM Shows Its Magic

This nanomedicine does not only directly kill tumor cells, but also actively modulates the tumor immune microenvironment by “reprogramming” immunosuppressive cells within tumors. Such tumor-associated macrophages, or TAMs, enable the immune system to better attack tumors. The FluidFM OMNIUM platform was crucial in revealing these interactions.

By precisely measuring adhesion forces between nanomedicines and cells, the team optimized nanomedicine design and performance. FluidFM also enabled real-time observation, revealing that nanomedicines dissociate and fragment in the acidic tumor microenvironment, improving penetration and retention.

3. In Vitro and In Vivo Experiments Validate Excellent Anti-Tumor Effects

In vitro, the team evaluated key nanomedicine performance metrics using FluidFM and other advanced technologies, showing excellent bioadhesion, photothermal conversion, and immunostimulatory activity. The nanomedicine promoted dendritic cell (DC) maturation and T cell activation, boosting anti-tumor immunity.

In vivo, intravenous delivery led to specific tumor targeting and retention. With photothermal irradiation, the nanomedicine efficiently ablated tumor tissue and induced lasting immune responses, preventing recurrence.

4. FluidFM: The Magic Wand of Single-Cell Research

In this research, FluidFM technology played an indispensable role in nanomedicine development. Like a magic wand at the microscale, the FluidFM cantilever allowed researchers to interact with individual cells with unprecedented precision.

This technology revealed how nanomedicines behave under different conditions, enabling discoveries that would otherwise remain invisible. This research, published in Biomaterials at the beginning of the year, demonstrates how FluidFM enables cutting-edge advances in nanomedicine and cancer immunotherapy.

Original article by Quantum Design China (QDC). Translated and republished with permission from QDC. Source: https://www.antpedia.com/ibook6212/n/608257-n.html