Nanomaterial Strategies Advance Cancer Immunotherapy, Studies Show

Recent studies and a review highlight the potential of nanomaterial-based strategies in cancer immunotherapy, including a nanoplatform that boosts immunogenic tumour cell death, nanosheet artificial antibodies with PD-L1 inhibitory and photothermal activity, and design principles for engineered nanomaterials.

A review published in Cancer Biology & Medicine in April 2026 by researchers from Nankai University examines how nanomaterials can be rationally engineered to overcome delivery barriers and strengthen cancer immunotherapy. The review notes that many nanoparticles rely on the enhanced permeability and retention (EPR) effect, but tumor accumulation is often heterogeneous in patients. To improve precision, researchers have developed active targeting strategies using ligands, antibodies, or receptor-recognition motifs that guide nanoparticles toward tumor cells, antigen-presenting cells, dendritic cells, macrophages, or T cells.

The review also highlights intracellular design strategies, including proton sponge effects, membrane fusion, and direct translocation, which help cargos escape endosomes and reach functional sites. Across the immunity cycle, nanoparticles can co-deliver tumor antigens and adjuvants to dendritic cells, enhance major histocompatibility complex class I (MHC-I)-mediated cross-presentation, and promote cytotoxic T lymphocyte activation. Other nanoplatforms are designed to block programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling, deliver messenger RNA encoding co-stimulatory molecules such as OX40, or carry CRISPR/Cas13a systems to disrupt immune escape pathways. The review also describes approaches to reprogram tumor-associated macrophages, deliver cytokines such as interleukin-12, relieve hypoxia, and reduce metabolic suppression.

The authors said nanomaterials should be viewed as immune-engineering tools, not simply miniature containers. They said the future of nano-immunotherapy will depend on matching material design with immune mechanism, so that each platform solves a defined biological bottleneck rather than adding complexity for its own sake. The review emphasizes that translation will require stronger evidence on tumor accumulation, intracellular trafficking, long-term safety, manufacturing consistency, and reproducibility.

In a study published in Nature Communications, researchers engineered a nanoplatform co-delivering siSTC1 and paclitaxel, in which paclitaxel is covalently conjugated to a sphingolipid and siSTC1 is electrostatically encapsulated (siSTC1/LNP-PTX). Stanniocalcin 1 (STC1) suppresses calreticulin (CRT) translocation by sequestering it within mitochondria, limiting immunogenic cell death (ICD) induction in tumours. Silencing STC1 enhances CRT surface exposure in Lewis lung carcinoma (LLC) cells when combined with paclitaxel, converting dying tumour cells into an in-situ vaccine that drives immunoprevention of tumour growth. The siSTC1/LNP-PTX system improves pharmacokinetics, synchronizes co-delivery to tumours, and enhances intratumoral exposure. Consequently, it amplifies CRT expression, promotes antigen-presenting cell-mediated phagocytosis and antigen presentation, and elicits robust cytotoxic T cell responses in LLC models. Moreover, siSTC1/LNP-PTX sensitizes tumours to PD-1 blockade.

Another study presented a facile approach for creating nanosheet artificial antibodies with both PD-L1 inhibitory activity and photothermal therapeutic activity for augmented cancer immunotherapy. Antibody-based PD-L1 checkpoint blockade has often shown limited therapeutic efficacy in clinical cancer treatment, and antibodies have limitations such as poor stability, long discovery time, and high cost. In the study, tripeptides with a nitriloacetate-Cu group were spontaneously assembled on WS2 or MoSe2 nanosheets via coordinate bonding, producing a variety of nanosheet antibody mimics. The nanosheet artificial antibodies selectively bound to PD-L1 with nanomolar affinity, enabling effective inhibition of the PD-1/PD-L1 signaling pathway. The multimodal MoSe2 nanosheet artificial antibody effectively killed tumor cells through PD-L1 blockade combined with a photothermal therapeutic effect, and the combination immunotherapy promoted the infiltration of antitumoral immune cells into solid tumors in mice, enhancing immunotherapeutic efficacy compared with monoclonal antibody treatment.