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Advanced strategies in liposomal cancer therapy: Problems and prospects of active and tumor specific drug release
Abstract
Tumor specific drug delivery has become increasingly interesting in cancer therapy, as the use of chemotherapeutics is often limited due to severe side effects. Conventional drug delivery systems have shown low efficiency and a continuous search for more advanced drug delivery principles is therefore of great importance. In the first part of this review, we present current strategies in the drug delivery field, focusing on site-specific triggered drug release from liposomes in cancerous tissue. Currently marketed drug delivery systems lack the ability to actively release the carried drug and rely on passive diffusion or slow non-specific degradation of the liposomal carrier. To obtain elevated tumor-to-normal tissue drug ratios, it is important to develop drug delivery strategies where the liposomal carriers are actively degraded specifically in the tumor tissue. Many promising strategies have emerged ranging from externally triggered light- and thermosensitive liposomes to receptor targeted, pH- and enzymatically triggered liposomes relying on an endogenous trigger mechanism in the cancerous tissue. However, even though several of these strategies were introduced three decades ago, none of them have yet led to marketed drugs and are still far from achieving this goal. The most advanced and prospective technologies are probably the prodrug strategies where non-toxic drugs are carried and activated specifically in the malignant tissue by overexpressed enzymes. In the second part of this paper, we review our own work, exploiting secretory phospholipase A2 as a site-specific trigger and prodrug activator in cancer therapy. We present novel prodrug lipids together with biophysical investigations of liposome systems, constituted by these new lipids and demonstrate their degradability by secretory phospholipase A2. We furthermore give examples of the biological performance of the enzymatically degradable liposomes as advanced drug delivery systems.
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“Dendrimers are one of the important classes of drug carriers and operate by encapsulating drugs in their unique macromolecular architecture.242”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [242]
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Metadata
- Authors
- Andresen, T. L., Jensen, S. S., & Jørgensen, K.
- Affiliations
- Technical University of Denmark (DK)
- Corresponding author
- Andresen, Thomas L.
- ORCID
- Andresen, Thomas L.
- Venue
- Progress in Lipid Research
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 44
- Issue
- 1
- Pages
- 68-97
- ISSN
- 0163-7827 (ISSN-L)
- OpenAlex
- W2065946609
- Cited by
- 580
- References
- 260
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 14 · 2023: 16 · 2022: 10 · 2021: 15 · 2020: 21 · 2019: 22 · 2018: 25 · 2017: 46 · 2016: 42 · 2015: 46 · 2014: 37 · 2013: 32 · 2012: 43
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Lipid Research (publishedVersion)
- PubMed (publishedVersion)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Keywords
- liposomal drug delivery, tumor-specific drug release, triggered drug release, secretory phospholipase A2, thermosensitive liposomes, cancer chemotherapy
- MeSH terms
- Antibodies, Antineoplastic Agents, Carrier Proteins, Cells, Hemolysis, Humans, Liposomes, Neoplasms, Phospholipases A, Prodrugs, Receptors, Cell Surface, Integrins, Drug Delivery Systems, Lipid Metabolism, Phospholipases A2, Folate Receptors, GPI-Anchored
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