Engineering nanoparticles to overcome barriers to immunotherapy

Abstract

Advances in immunotherapy have led to the development of a variety of promising therapeutics, including small molecules, proteins and peptides, monoclonal antibodies, and cellular therapies. Despite this wealth of new therapeutics, the efficacy of immunotherapy has been limited by challenges in targeted delivery and controlled release, that is, spatial and temporal control on delivery. Particulate carriers, especially nanoparticles have been widely studied in drug delivery and vaccine research and are being increasingly investigated as vehicles to deliver immunotherapies. Nanoparticle‐mediated drug delivery could provide several benefits, including control of biodistribution and transport kinetics, the potential for site‐specific targeting, immunogenicity, tracking capability using medical imaging, and multitherapeutic loading. There are also a unique set of challenges, which include nonspecific uptake by phagocytic cells, off‐target biodistribution, permeation through tissue (transport limitation), nonspecific immune‐activation, and poor control over intracellular localization. This review highlights the importance of understanding the relationship between a nanoparticle's size, shape, charge, ligand density and elasticity to its vascular transport, biodistribution, cellular internalization, and immunogenicity. For the design of an effective immunotherapy, we highlight the importance of selecting a nanoparticle's physical characteristics (e.g., size, shape, elasticity) and its surface functionalization (e.g., chemical or polymer modifications, targeting or tissue‐penetrating peptides) with consideration of its reactivity to the targeted microenvironment (e.g., targeted cell types, use of stimuli‐sensitive biomaterials, immunogenicity). Applications of this rational nanoparticle design process in vaccine development and cancer immunotherapy are discussed.

Using immunotherapy to boost the abscopal effect

“…A recent review highlights studies showing that the use of nanoparticles to deliver immunotherapy can boost antitumour immune responses 77 . In one study using a mouse model of melanoma, targeted delivery of CpG oligodeoxynucleotides by nanoparticles to DCs in the draining lymph node increased the CD8 + T cell:T reg cell ratio, delaying tumour growth compared with mice receiving immune adjuvant-free nanoparticles 78 .…”

“…It has been demonstrated that the use of targeted biocompatible gold nanoparticles loaded with immunotherapeutic agents can improve the delivery and safety of immunotherapy 77 . The use of such high-atomic-number nanoparticles could also avail efforts to minimize radiation toxicity 2 .…”

Colloidal capsules: nano- and microcapsules with colloidal particle shells

“…Additionally, the reports of more and more pre-clinical systems tailored for drug-delivery applications of nanocarriers emphasize the need for other nanomedical agents than just tumors 388 in the future, e.g. for cancer immunotherapy 389 or the treatment of endothelial disorders 390 and pulmonary diseases. 391…”

CXCL5 Modified Nanoparticle Surface Improves CXCR2+ Cell Selective Internalization

“…The search for nanomaterials (NMs) with the ability to travel to specific biological tissues is constantly increasing. Several nanoparticles (NP) engineering methods [1] as well as specific corona formation [2] have been tested thus far. However, many physical, chemical, or biological barriers limit their successful application.…”