4.2.1. NP Conjugates

One of the novel applications of NPs is their possible role as immunomodulating agents for the treatment of patients with cancer or auto-immune disorders. Liposomal or polymer NPs are designed to mimic biological interactions between APCs and T cells, which can also act as specific subcellular granules to promote anti-tumour immunity [193]. One example is polydimethylsiloxane (PDMS) particles, modified with antibodies to CD3 and CD28, which activate and enhance the in vitro expansion of TCD4+ and CD8+ cells [196].

For instance, NPs could also be designed for direct dependency on immune cells to target and attack different tumour cells [193]. For example, different NPs loaded with chemotherapeutic agents that reduce local recurrences may be delivered via neutrophils, as these cells will be recruited to the tumour resection bed by the inflammatory cytokines released after surgery in the case of brain tumours [197]. Other types of innate immune response cells, such as platelets conjugated with anti-PD-L1 antibodies on their membrane, which also accumulate in the tumour bed after surgery, can also be used to reduce local recurrence [198].

It should be noted that various studies have revealed the importance of the size, shape, density, rigidity and spatial organization of the MHC, among other characteristics [193], since it has been shown that, in the case of NPs used as a substrate for artificial APCs, their size is fundamental for the activation of T cells [2,199].

Another employed NPs are super-paramagnetic, such as those based on fucoidan-dextran, which can be modified with antibodies that inhibit PD-L1 and activate T cells to generate a multifunctional complex. Hence, magnetic field orientation in vivo towards the tumour is achieved by the properties of the nucleus and its effect outside the nucleus is minimised, while the tumour immune response is enhanced by the above-mentioned antibodies [200].

Beyond the modification of nanomaterial compositions, the NPs can also be engineered to enhance tumour cell phagocytosis and subsequent antigenic presentation by macrophages. For example, in HER2-positive breast cancer, bio-specific nanoparticle systems that recruit macrophages to tumour cells with the HER2 receptor can be used [201].

Taking into account the multiple possibilities of conjugation of the nanomaterials and biomolecules described above to design NPs, some of the most important ones, such as aAPCs or iron oxide NPs, are described below. In addition, exosomes, which are nanovesicules that come from cells and transmit information between tissue microenvironments, will be reviewed [202]. In other words, exosomes are vesicles of completely natural origin that can also be used in nanomedicine.
