TINY CARRIERS TO FAST-TRACK CANCER VACCINE DELIVERY

Polymeric nanoparticles are used for drug encapsulation and faster tracking.

Smaller, smarter cancer vaccines

Anti-cancer strategies could soon become more selective and less toxic thanks to nanomaterials. A survey by researchers from Saudi Arabia including at KAIMRC in collaboration with the Jamia Hamdard centre in New Delhi, India, shows that tiny self-assembled lipid and polymer-based objects, or nanocarriers, could aid therapeutics by making cancer vaccines easier to deliver to specific sites in the body.

Although some vaccines, known as prophylactic vaccines, can prevent cancers caused by viruses in healthy people, such as the human papilloma virus, most cancer vaccines are used to treat patients who are already affected by the disease. These therapeutic vaccines, which are usually antigens derived from patient cancer cells, trigger an immune response that results in an attack on cancer cells.

Cancer vaccines are highly effective but difficult to introduce into target organs and cells because they comprise negatively charged nucleic acids with high molecular weights. Vaccine formulation and storage also affect their performance and safety.

There are several methods available for targeted cancer vaccine delivery. First-generation vaccines relied on viruses, such as herpes simplex viruses and adenoviruses, to carry the cancer cell-specific antigens. However, this approach increases the risks of mutagenesis, carcinogenesis, and unexpected immune reactions.

Nanocarriers such as liposomes and nanoparticles are promising substitutes for viral carriers. Easy to manufacture and modify using a variety of functional groups, they provide multiple ways to encapsulate nucleic acids and release them at the desired sites. Specifically, lipid- and polymer-based nanocarriers can readily penetrate cell membranes and expedite the transfection process. These carriers are electrostatic complexes between positively charged lipids or polymers and negatively charged nucleic acids.

Vaccine delivery using lipid-based complexes hinges on the hydrophobic domain of the lipids, which mediates the transmembrane transport of the nucleic acids and shields them from enzymes present in target cells. After cell entry, the complexes can directly release their cargo into the cytoplasm. Polymer-based complexes require an additive to help rupture the endosomes formed during cell entry. Highly branched polymers usually form smaller particles than their linear analogues, which boost their performance.

Nanocarriers have been used for two decades in genetic vaccine delivery against various cancers, including breast, colon, and cervical cancer. In particular, poly(ethyleneimine) complexes effectively transfected a small RNA antigen targeting breast cancer, inhibiting tumor growth. Albumin-contained liposomes used to deliver the drug vinblastine with a gene–prodrug mixture showed a synergistic antitumor effect against mammary adenocarcinoma cells.

The researchers are now developing new nanocarrier-based formulations to allow cancer vaccines to reach their full potential.

Beg, S. et al. Lipid/polymer-based nanocomplexes in nucleic acid delivery as cancer vaccines. Drug Discovery Today (2021). Advance online publication, 18 February 2021.