Nanomaterials for Tumor Microenvironment Modulation in Cancer Therapy

The tumour microenvironment encompasses a complex interplay of extracellular matrix, stromal cells, aberrant vasculature, acidic pH, hypoxia and immunosuppressive factors that together hinder conventional cancer treatments. Nanomaterials offer sophisticated strategies to remodel this milieu by responding to its unique biochemical cues or by actively altering its properties. Metal oxide nanoparticles, liposomal nanozymes, polymeric carriers and hybrid constructs have been developed to alleviate hypoxia through in situ oxygen generation, to neutralise acidic niches via pH‐responsive dissolution, and to produce reactive oxygen species (ROS) for chemodynamic therapy. Surface engineering with targeting ligands or biomimetic coatings improves tumour penetration and retention, while co‐delivery of chemotherapeutic agents and photosensitisers enables synergistic chemo‐photodynamic or chemo‐photothermal regimens. More recently, multifunctional platforms have been designed to reprogramme the immunosuppressive microenvironment, promoting antigen presentation and T‐cell infiltration. Together, these advances illustrate a shift from passive drug carriers towards dynamic nanoregulators that reshape physical and biochemical barriers, offering more precise, multimodal and immune‐engaging interventions against solid malignancies.

Research from Nature Portfolio

A seminal biodegradable hollow manganese dioxide nanoshell has been engineered for tumour‐responsive imaging, on‐demand drug release and microenvironmental modulation. The hollow MnO₂ framework is surface‐modified with polyethylene glycol and co‐loaded with a photodynamic agent and a chemotherapeutic drug. Within the acidic tumour niche, the shell disintegrates to release its cargos and catalyses endogenous hydrogen peroxide decomposition, relieving hypoxia. This dual action enhances photodynamic efficacy, potentiates chemotherapy and primes robust antitumour immune responses. Remarkably, when combined with checkpoint‐blockade therapy, distant metastases are suppressed, highlighting the potential of microenvironment‐targeted nanoplatforms to extend both local and systemic therapeutic benefit.

Nanomaterials for Tumor Microenvironment Modulation in Cancer Therapy publication trend

The graph below shows the total number of articles in nanomaterials for tumor microenvironment modulation in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Tumour microenvironment (TME): The collective network of cells, matrix and physicochemical conditions surrounding a tumour that influences its progression and response to therapy.

Photodynamic therapy (PDT): A treatment modality using light‐activated compounds to generate cytotoxic species that induce tumour cell death.

Chemodynamic therapy (CDT): A strategy employing nanomaterials to catalyse chemical reactions in the TME, producing reactive oxygen species to kill cancer cells.

Reactive oxygen species (ROS): Highly reactive oxygen derivatives that can damage cellular components and trigger programmed cell death.

pH‐responsive nanomaterial: An engineered nanoparticle designed to alter its structure or release cargo in response to acidic conditions characteristic of tumours.

References

1. Recent development of pH‐responsive theranostic nanoplatforms for magnetic resonance imaging‐guided cancer therapy. Exploration (2023).
2. Biomimetic liposomal nanozymes improve breast cancer chemotherapy with enhanced penetration and alleviated hypoxia. Journal of Nanobiotechnology (2023).
3. Recent advances in Fenton and Fenton-like reaction mediated nanoparticle in cancer therapy. Biomedical Technology (2023).
4. Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses. Nature Communications (2017).
5. Multifunctional Nanoregulator Reshapes Immune Microenvironment and Enhances Immune Memory for Tumor Immunotherapy. Advanced Science (2019).