Light activated liposomes for cancer therapy

Dr. T. Lajunen1), University Helsinki/Finland

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1.

Dr. Tatu LajunenDivision of Pharmaceutical Biosciences, Faculty of Pharmacy, University Helsinki, Helsinki/Finland

Abstract

Major shift towards biological drugs, like proteins and RNAi compounds, is taking place in the pharmaceutical industry. These drugs benefit from intracellular targeted drug delivery systems, because low intracellular bioavailability prevents utilization of these compounds in the clinical applications. Furthermore, targeted drug delivery is needed in the treatment of some diseases that are affecting difficult-to-reach targets (retina, brain) or for the delivery of drugs that cause serious adverse effects (cytostatics). Liposomes have been used to deliver drugs (e.g. in. cancer treatment), but drug release at target cells and tissues is poorly controlled and erratic. The approach applied in this project is to use light triggered liposomes for effective drug release with spatial and temporal specificity. The new formulation in this project is composed of FDA and EMA approved compounds (phospholipids, indocyanine green). The triggered release is achieved with a near IR light, which is safer and has better tissue penetration than visible or UV light.1)2)3) The traditional ‘stealth’ compound polyethylene glycol (PEG) was replaced by endogenous hyaluronic acid (HA), which offers benefits related to immunogenicity, stability, and active targetability to receptors over-expressing cancer cells.4) The liposomes will be investigated for drug delivery to tumors in a multidisciplinary consortium with expertise in chemistry, biology, pharmacology, laser technology, and drug development.

The research conducted in this project can be summarized into three main points:

  1. Time and location-controlled drug release with triggered DDSs, which would enable efficient release of larger molecules without compromising the stability at off-target locations.
  2. The use of nanoparticle coatings for specific applications. These are especially dual-purpose ligands on the DDS’s surface that actively target specific cancer cells and enhance the stability of the drug in vivo.
  3. New research methods to deal with the difficulty of testing the complex phenomena of biomacromolecule delivery with methods that are repeatable, tunable and do not use animal. This approach focuses on “body-on-chip” flow culture systems, which have so far seen only limited use in liposome research.

Benefit for the community

This project investigates light activated drug delivery systems in the context of cancer drug delivery. The developed countries, like Finland, struggle with aging society, which emphasizes specific disease conditions of the elderly. Namely, the cancer has become one of the most prevalent causes of death (over 25%). Currently, about 1/3 of the new accepted medicines are proteins and the importance of other biologicals is increasing. Even though the pharmacologic efficacy of the compounds may be excellent, they permeate only poorly to the sites of action. Thus, drug delivery is one of the most critical challenges of current drug research. Co-operating research tackling these problems would increase the well-being of numerous people. The use of organ-on-chip technology for liposome research enables controllable way to produce in vivo relevant data faster, cheaper, and with less ethical problems. Conducting a proof of concept research with liposomes on organ-on-chip may encourage the use of the method in industry leading to faster drug development and cheaper drugs for the public. This is important especially for liposomal drug carriers, as the development costs of sophisticated nanoparticles are substantial. The principle and technologies of this project may also be useful for other applications beyond liposomal research.

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References:
1.
Lajunen T, Kontturi L, Viitala L, Róg T, Bunker A, Laaksonen T, Viitala T, Murtomäki L, Urtti A, 2016
Indocyanine green liposomes for light triggered drug release
Mol. Pharm. 13, 2095–2107
2.
Lajunen T, Nurmi R, Wilbie D, Ruoslahti T, Johansson NG, Korhonen O, Rog T, Bunker A, Ruponen M, Urtti A, 2018
The effect of light sensitizer localization on the stability of indocyanine green liposomes
J. Control. Release 28, 213-223
3.
Kari O, Ndika J, Parkkila P, Louna A, Lajunen T, Puustinen A, Viitala T, Alenius H, Urtti A, 2020
In situ analysis of liposome hard and soft protein corona structure and composition in a single label-free workflow
Nanoscale 12, 1728-1741
4.
Mattheolabakis G, Milane L, Singh A, Amiji MM, 2015
Hyaluronic acid targeting of CD44 for cancer therapy: from receptor biology to nanomedicine
J. Drug Target. 23, 605-618
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