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Home > Nanotechnology Columns > Polymerically Yours > Killing Cancer with LPNs

Adam Alonzi

Lipid-polymer nanoparticles show great potential in treating cancer.

February 26th, 2015

Killing Cancer with LPNs

Comparison of Nanomaterials

Nanoparticle delivery systems promise to resolve a number of problems associated with conventional pharmaceuticals. Liposomes are lauded for their biocompatibility, but are constrained by their short shelf life. Polymeric nanoparticles are stable, but not as biocompatible. Thus researchers have been exploring ways to combine these two methods to produce superior amalgams. These amalgams are called lipid-polymer hybrid nanoparticles (LPNs). LPNs normally have a polymeric center in which the desired molecules are stored. To this a layer of polyethylene glycol can be added, which confers yet another layer of biofriendly stealth while the little dispensers weave and bob their way through the bloodstream. LPNs can target particular types of cells. This makes them excellent candidates for treating cancer.

LPNs are generally prepared in one of two ways. In the first they are made separately and then fused by hydration or sonication. Extrusion, a process too technical to be adequately summarized here, is also used in their manufacture. It is fortunate the electrostatic charges of the anionic polymers and the cationic lipids assist one another in coming together. In the single-step approach the two are prepared and join together through self-assembly. In the emulsion method the polymer and drug are dissolved together in a suitable medium and dispersed through heat and/or stirring. While this may sound like an awful lot of work (or very little depending on your background), LPNs are more than worth the trouble. Because multiple layers can be produced radically different sorts of drugs can be packed into a tiny and customizable package.

LPNs show less leakage and allow for sustained release. Cytotoxic drugs have been used for some time to treat cancer, but many of them are hydrophobic, have a shoddy half-life and are toxic to healthy cells. Yet these problems can be solved by packing them into an LPN. Zhang and his team demonstrated this when they used this technology to deliver docetaxel to cancer cells. In the experiments the particles displayed the desired properties and destroyed the targets by seeking out those overexpressing a particular antigen. Using multiple drugs at once, as Su did, is another useful application of this technology. 2′-deoxy-5-azacytidine, DAC, an epigenetic drug, reactivates (or keeps active) tumor suppressor genes by inhibiting DNA Methyltransferases. As their name suggests, these enzymes are responsible for the methylation (silencing) of genetic sequences.

Nanoparticles are useful in avoiding multidrug resistance by making it easier to induce apoptosis―cell death. Smaller amounts are needed because the mechanism makes it more effective. This can be compounded further when multiple molecules with positive interactions are put into the mix. The cancer itself can be fought as well as the microenvironment it is using to spread. For instance, evidence strongly suggests malignancies can recruit leukocytes to produce angiogenic and cellular growth factors. To address this, researchers like Sengupta have designed sequential delivery systems. His team's brainchild released an anti-angiogenic drug and then doxorubicin, an antitumorigenic agent used most often to treat leukemia and Hodgkin's lymphoma.

Yet the majority of cancer deaths, approximately 9 in 10, are due to metastasis.. Curcumin, a pharmacologically active compound found in turmeric, has been tested on a number of cancers. Its bioavailability, even in doses of up to 12g a day, is quite poor. It decreases vascular inflammation and the movement of malignant cells. By doing this, metastasis was slowed. Mieszawska's LPNs contained doxorubicin and sorafenib. They released the drug steadily for 20 days and inhibited the proliferation of LS174T cancer cell lines. Furthermore, tomographic imaging showed a far greater accumulation of particles in the tumor than in healthy tissue. This is encouraging since specificity in this instance is almost synonymous with safety. Currently speculative modifications will improve targeting. Shells coated with biological membranes will likely lead to improved precision. Lipids taken from biological membranes may be superior to stealth materials like PEG. Although much more work needs to be done and it will likely be years before they are commonplace, LPNs show great promise.

Krishnamurthy, Sangeetha, et al. "Lipid-coated polymeric nanoparticles for cancer drug delivery." Biomaterials Science (2015). Link.

Pathak, Yashwant, and Deepak Thassu. Drug Delivery Nanoparticles Formulation and Characterization. New York: Informa Healthcare, 2009. Print. Drug Delivery Nanoparticles Formulation and Characterization

Zhang, Liangfang, et al. "Self-assembled lipid− polymer hybrid nanoparticles: a robust drug delivery platform." ACS nano 2.8 (2008): 1696-1702. Link.

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