Nanoparticle-Mediated Antigen Delivery in Cancer Immunotherapy

Cancer immunotherapy harnesses the body’s immune system to recognise and eliminate tumour cells by presenting tumour-associated antigens to T lymphocytes. Nanoparticle-mediated antigen delivery employs nanoscale carriers—such as polymeric particles, liposomes and inorganic platforms—to encapsulate or adsorb antigenic peptides, proteins or nucleic acids and co-deliver immunostimulatory agents. These carriers protect cargo from degradation, facilitate targeted transport to antigen-presenting cells (APCs) and promote efficient intracellular routing for cross-presentation on major histocompatibility complex class I molecules. By tailoring physicochemical properties such as size, surface charge and ligand decoration, nanoparticles can preferentially accumulate in lymphoid organs or the tumour microenvironment, enhance dendritic cell maturation and drive robust cytotoxic T lymphocyte responses. Inclusion of adjuvants—such as synthetic RNA analogues or Toll-like receptor ligands—further amplifies antigen-specific immunity. This approach underpins personalised cancer vaccines, combination regimens with immune checkpoint blockade and strategies to overcome immunosuppressive niches within solid tumours, offering a versatile platform for next-generation oncological treatments.

Research from Nature Portfolio

Recent studies have demonstrated the potent synergy between biodegradable polymeric particles and defined adjuvants in eliciting anti-tumour responses. One seminal work developed poly(lactic-co-glycolic acid) (PLGA) nanoparticles co-encapsulating tumour antigens and a pharmaceutically defined double-stranded RNA adjuvant. Upon uptake by dendritic cells, these particles induced potent activation of both murine and human APCs, leading to elevated expansion of antigen-specific CD8+ T cells. In preclinical models, vaccination with these particles resulted in marked tumour growth retardation, prevention of metastatic spread and prolonged survival. Therapeutic efficacy was further amplified by concurrent administration of immune checkpoint inhibitors, which reinvigorated T cell cytotoxicity and achieved complete tumour clearance in resistant models.

Nanoparticle-Mediated Antigen Delivery in Cancer Immunotherapy publication trend

The graph below shows the total number of articles in nanoparticle-mediated antigen delivery in cancer immunotherapy across all publications each year (not limited to Nature Index journals).

Technical terms

Nanoparticle: A particulate carrier with dimensions in the 1–1000 nm range used to transport therapeutic cargos.

Antigen cross-presentation: The process by which APCs present exogenous antigens on MHC class I molecules to CD8+ T cells.

Dendritic cell: A professional APC that captures, processes and presents antigens to T lymphocytes, initiating adaptive immunity.

PLGA: Poly(lactic-co-glycolic acid), a biodegradable polymer commonly used for controlled drug and antigen release.

Toll-like receptor ligand: A molecular adjuvant that activates innate immune receptors to enhance APC maturation.

Immune checkpoint blockade: Therapeutic antibodies that inhibit regulatory pathways (e.g., PD-1/PD-L1) to sustain T cell activity.

Tumour microenvironment: The cellular and molecular milieu surrounding a tumour, which can support or suppress immune responses.

References

1. Nanomaterials in tumor immunotherapy: new strategies and challenges. Molecular Cancer (2023).
2. PLGA-particle vaccine carrying TLR3/RIG-I ligand Riboxxim synergizes with immune checkpoint blockade for effective anti-cancer immunotherapy. Nature Communications (2021).
3. PLGA Nanoparticles Co-encapsulating NY-ESO-1 Peptides and IMM60 Induce Robust CD8 and CD4 T Cell and B Cell Responses. Frontiers in Immunology (2021).
4. Delivery of Immunostimulatory Cargos in Nanocarriers Enhances Anti-Tumoral Nanovaccine Efficacy. International Journal of Molecular Sciences (2023).