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Polymeric micelles in anticancer therapy: targeting, imaging and triggered release.

Oerlemans C, Bult W, Bos M, Storm G, Nijsen JF, Hennink WE - Pharm. Res. (2010)

Bottom Line: Micelle-based drug delivery, however, can be improved in different ways.Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies.The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a 'magic bullet' a major step forward.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology and Nuclear Medicine, University Medical Center, Heidelberglaan 100, Utrecht, The Netherlands. C.Oerlemans@umcutrecht.nl

ABSTRACT
Micelles are colloidal particles with a size around 5-100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use in patients with breast cancer. Micelle-based drug delivery, however, can be improved in different ways. Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies. Moreover, pH-, thermo-, ultrasound-, or light-sensitive block copolymers allow for controlled micelle dissociation and triggered drug release. The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a 'magic bullet' a major step forward.

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Related in: MedlinePlus

Schematic drawing of polymeric micelle (a). Micelle conjugated with a targeting ligand (b). Micelle containing an incorporated contrast agent or chelated imaging moieties (c). Micelle modified for triggered drug release (d). Either the hydrophilic or hydrophobic polymer can be rendered thermo/pH/light/ultrasound-sensitive. Optimized micelle for anticancer therapy, bearing targeting ligands, contrast agents or imaging moieties, therapeutic drugs and polymers suitable for triggered, controlled release (e).
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Fig1: Schematic drawing of polymeric micelle (a). Micelle conjugated with a targeting ligand (b). Micelle containing an incorporated contrast agent or chelated imaging moieties (c). Micelle modified for triggered drug release (d). Either the hydrophilic or hydrophobic polymer can be rendered thermo/pH/light/ultrasound-sensitive. Optimized micelle for anticancer therapy, bearing targeting ligands, contrast agents or imaging moieties, therapeutic drugs and polymers suitable for triggered, controlled release (e).

Mentions: Cancer is a leading cause of death world-wide and is responsible for approximately 13% of all deaths, according to the World Health Organization (1). In Europe alone, Ferlay et al. recently estimated that in 2008 1.7 million cancer deaths occurred, and 3.2 million cancer cases were diagnosed (2). Although prognosis is better now, the large variety of cancer types and metastases makes treatment very difficult. Surgical resection is the treatment of choice, since this treatment is usually curative. Surgery, however, is not an option in many patients due to the tumor size, location and presence of metastases. External beam radiotherapy is also considered a curative treatment option. However, not all tumors are eligible for this therapy due to motion of the tumor-bearing tissue or the adjacency of radiosensitive organs. Another frequently used therapy is systemic chemotherapy, but although chemotherapeutic agents are becoming more and more specific, many of the clinically used chemotherapeutics require high tissue concentrations, which are frequently associated with systemic toxicity. A very promising approach to overcome systemic toxicity is the application of drug-loaded nanosized drug carriers, such as liposomes, polymeric nanoparticles, dendrimers and micelles (3–5). The incorporation of chemotherapeutic agents into nanosized drug carriers has several advantages compared to systemic chemotherapy. First, low-molecular-weight drugs are mostly rapidly eliminated by liver and/or kidneys. By loading them in stealth nanoparticles, their bioavailability substantially increases. (6). Second, due to their small size, nanosized drug carriers are passively targeted to the tumors by the enhanced permeability and retention (EPR) effect, leading to a higher drug concentration at the tumor site and decreased toxicity compared with systemic administration (7). Third, hydrophobic drugs can only be administered intravenously (i.v.) after addition of solubilizing adjuvants like ethanol or Cremophor EL, which is often accompanied with toxic side effects (8,9). Incorporation of these drugs in micelles avoids the use of adjuvants (10). This review will focus on micelles as a nanosized drug carrier system for cancer therapy and their modifications for tumor targeting, multimodality imaging and triggered release (Fig. 1).Fig. 1


Polymeric micelles in anticancer therapy: targeting, imaging and triggered release.

Oerlemans C, Bult W, Bos M, Storm G, Nijsen JF, Hennink WE - Pharm. Res. (2010)

Schematic drawing of polymeric micelle (a). Micelle conjugated with a targeting ligand (b). Micelle containing an incorporated contrast agent or chelated imaging moieties (c). Micelle modified for triggered drug release (d). Either the hydrophilic or hydrophobic polymer can be rendered thermo/pH/light/ultrasound-sensitive. Optimized micelle for anticancer therapy, bearing targeting ligands, contrast agents or imaging moieties, therapeutic drugs and polymers suitable for triggered, controlled release (e).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2982955&req=5

Fig1: Schematic drawing of polymeric micelle (a). Micelle conjugated with a targeting ligand (b). Micelle containing an incorporated contrast agent or chelated imaging moieties (c). Micelle modified for triggered drug release (d). Either the hydrophilic or hydrophobic polymer can be rendered thermo/pH/light/ultrasound-sensitive. Optimized micelle for anticancer therapy, bearing targeting ligands, contrast agents or imaging moieties, therapeutic drugs and polymers suitable for triggered, controlled release (e).
Mentions: Cancer is a leading cause of death world-wide and is responsible for approximately 13% of all deaths, according to the World Health Organization (1). In Europe alone, Ferlay et al. recently estimated that in 2008 1.7 million cancer deaths occurred, and 3.2 million cancer cases were diagnosed (2). Although prognosis is better now, the large variety of cancer types and metastases makes treatment very difficult. Surgical resection is the treatment of choice, since this treatment is usually curative. Surgery, however, is not an option in many patients due to the tumor size, location and presence of metastases. External beam radiotherapy is also considered a curative treatment option. However, not all tumors are eligible for this therapy due to motion of the tumor-bearing tissue or the adjacency of radiosensitive organs. Another frequently used therapy is systemic chemotherapy, but although chemotherapeutic agents are becoming more and more specific, many of the clinically used chemotherapeutics require high tissue concentrations, which are frequently associated with systemic toxicity. A very promising approach to overcome systemic toxicity is the application of drug-loaded nanosized drug carriers, such as liposomes, polymeric nanoparticles, dendrimers and micelles (3–5). The incorporation of chemotherapeutic agents into nanosized drug carriers has several advantages compared to systemic chemotherapy. First, low-molecular-weight drugs are mostly rapidly eliminated by liver and/or kidneys. By loading them in stealth nanoparticles, their bioavailability substantially increases. (6). Second, due to their small size, nanosized drug carriers are passively targeted to the tumors by the enhanced permeability and retention (EPR) effect, leading to a higher drug concentration at the tumor site and decreased toxicity compared with systemic administration (7). Third, hydrophobic drugs can only be administered intravenously (i.v.) after addition of solubilizing adjuvants like ethanol or Cremophor EL, which is often accompanied with toxic side effects (8,9). Incorporation of these drugs in micelles avoids the use of adjuvants (10). This review will focus on micelles as a nanosized drug carrier system for cancer therapy and their modifications for tumor targeting, multimodality imaging and triggered release (Fig. 1).Fig. 1

Bottom Line: Micelle-based drug delivery, however, can be improved in different ways.Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies.The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a 'magic bullet' a major step forward.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology and Nuclear Medicine, University Medical Center, Heidelberglaan 100, Utrecht, The Netherlands. C.Oerlemans@umcutrecht.nl

ABSTRACT
Micelles are colloidal particles with a size around 5-100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use in patients with breast cancer. Micelle-based drug delivery, however, can be improved in different ways. Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies. Moreover, pH-, thermo-, ultrasound-, or light-sensitive block copolymers allow for controlled micelle dissociation and triggered drug release. The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a 'magic bullet' a major step forward.

Show MeSH
Related in: MedlinePlus