The oldest problem in cancer treatment

Chemotherapy drugs kill dividing cells. Cancer cells divide. So do cells in your hair follicles, gut lining and bone marrow. That is why chemotherapy causes hair loss, nausea and low blood counts: the drug goes everywhere, and it cannot tell the difference.

For decades, one of the central goals of cancer research has been to deliver the drug to the tumour and nowhere else. This second series on Peptide Nano-Chemistry and Nanotechnology looks at how peptides are being used to try, starting with Chapter 7, written by researchers at the Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences.

The title of this series includes "Read With Care" for a reason. The science is fascinating. But almost all of it is at the laboratory and animal stage, and the gap between a result in a mouse and a treatment for a person is wide. Part 7 is devoted to that gap.

The basic idea: nanoparticle plus peptide

The strategy described in Chapter 7 has two parts.

A carrier: a tiny particle that holds the drug. The chapter covers many kinds: biodegradable polymers like PLGA (which breaks down into lactic and glycolic acid, which the body can process), PEG, chitosan (from crustacean shells), liposomes (tiny fat bubbles), protein particles made from human serum albumin, and even particles wrapped in cell membranes.

A targeting peptide: a short sequence attached to the carrier's surface that binds a receptor found more often on cancer cells or tumour blood vessels.

The peptide acts like an address label. The carrier is the envelope.

The address labels

The chapter and its extensive tables list dozens of targeting peptides. A few that come up repeatedly are worth knowing:

  • RGD (arginine-glycine-aspartate). Binds integrins, receptors that are overactive on some tumour cells and on the new blood vessels tumours grow. The chapter describes RGD-coated chitosan particles taken up more by breast cancer cells with high levels of the target integrin.
  • iRGD. A clever variant that first binds integrins and then, after being cut, binds a second receptor (neuropilin-1) that helps it penetrate deeper into tumour tissue.
  • GE11. Binds the epidermal growth factor receptor (EGFR), overexpressed in several cancers.
  • p28. A cell-penetrating fragment of azurin, a bacterial protein. The chapter describes p28-coated particles designed to target lung cancer cells.
  • Angiopep. Designed to help carriers cross the blood-brain barrier, used in the book's examples for glioma, a brain tumour.
  • Peptides that bind PD-L1, a protein some tumours use to switch off immune attack. Blocking it is the basis of an important class of immunotherapy drugs.

The drugs being carried

The payloads are mostly established chemotherapy drugs: doxorubicin, paclitaxel, irinotecan, 5-fluorouracil, sorafenib, platinum drugs. Some examples carry genetic material instead, like microRNA. Others carry agents for photothermal therapy (heating tumours with light) or photodynamic therapy (activating a toxic molecule with light).

The idea is not to invent new cancer-killing chemistry. It is to take drugs that already work and make them go to the right place.

Examples from the chapter

A few studies give a sense of the approach:

  • Neuroblastoma. A peptide combining a tissue-penetrating motif with a neuroblastoma-targeting sequence was attached to doxorubicin-loaded liposomes. It improved tumour binding and anti-tumour effect in three animal models.
  • Breast cancer. Liposomes carrying the peptide LinTT1 and loaded with both doxorubicin and sorafenib enhanced the effect of the two drugs in two breast cancer cell lines.
  • Colon cancer. Particles combining a cell-penetrating motif, a tumour blood vessel ligand and a mitochondria-targeting motif, coated with a pH-sensitive layer, released irinotecan and a microRNA inside colon cancer cells, with effective treatment in mice.
  • Colorectal cancer and radiation. Albumin nanoparticles carrying 5-fluorouracil and a peptide found by screening in patient-derived tumours increased complete tumour response to radiotherapy in a resistant model.

The quiet assumption

There is a concept underlying much of this field that the chapter mentions: the EPR effect (enhanced permeability and retention). Tumour blood vessels are often leaky, so nanoparticles can slip out of the bloodstream into tumour tissue, and poor drainage keeps them there.

EPR is real in many mouse tumours. In human tumours, it turns out to be much more variable, and this is one widely discussed reason nanomedicines that looked excellent in mice have often disappointed in people. A general reader should know that "targeted nanoparticle" does not guarantee that most of the drug reaches the tumour. In many studies, only a small fraction does.

Why this matters to you

Targeted delivery is one of the most important ideas in modern cancer research, and peptides are among the most versatile tools for it. They are small, can be designed and made precisely, and can bind receptors that distinguish diseased cells from healthy ones.

Some of this has already reached patients in related forms. Peptide-targeted radioactive treatments, for example, use peptides that bind receptors on certain neuroendocrine and prostate tumours to deliver radiation directly to cancer cells. That shows the principle can work.

But when you read about a new "targeted nanoparticle" for cancer, keep asking the question at the heart of this series: was this in cells, in mice, or in people? The next parts look at increasingly clever designs, and Part 7 looks honestly at why so few reach the clinic.

This series explains biomedical research for general readers. Most approaches described are at the laboratory or animal study stage and are not available treatments. Nothing here is medical advice. Anyone affected by cancer should rely on their oncology team.