Cationic dendritic starch as a vehicle for photodynamic therapy and siRNA co-delivery

Sarah A. Engelberth, Nadine Hempel, Magnus Bergkvist

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Cationic enzymatically synthesized glycogen (cESG) is a naturally-derived, nano-scale carbohydrate dendrite that has shown promise as a cellular delivery vehicle owing to its flexibility in chemical modifications, biocompatibility and relative low cost. In the present work, cESG was modified and evaluated as a vehicle for tetraphenylporphinesulfonate (TPPS) in order to improve cellular delivery of this photosensitizer and investigate the feasibility of co-delivery with short interfering ribonucleic acid (siRNA). TPPS was electrostatically condensed with cESG, resulting in a sub-50 nm particle with a positive zeta potential of approximately 5 mV. When tested in normal ovarian surface epithelial and ovarian clear cell carcinoma cell culture models, encapsulation of TPPS in cESG significantly improved cell death in response to light treatment compared to free drug alone. Dosages as low as 0.16 μM TPPS resulted in cellular death upon illumination with a 4.8 J/cm2 light dosage, decreasing viability by 96%. cESG-TPPS was then further evaluated as a co-delivery system with siRNA for potential combination therapy, by charge-based condensation of an siRNA directed at reducing expression of manganese superoxide dismutase (Sod2) as a proof of principle target. Simultaneous delivery of TPPS and siRNA was achieved, reducing Sod2 protein expression to 48%, while maintaining the photodynamic properties of TPPS under light exposure and maintaining low dark toxicity. This study demonstrates the versatility of cESG as a platform for dual delivery of small molecules and oligonucleotides, and the potential for further development of this system in combination therapy applications.

Original languageEnglish (US)
Pages (from-to)185-192
Number of pages8
JournalJournal of Photochemistry and Photobiology B: Biology
Volume168
DOIs
StatePublished - Mar 1 2017

Fingerprint

glycogens
ribonucleic acids
starches
Photochemotherapy
Glycogen
Starch
therapy
delivery
vehicles
RNA
Light
death
dosage
Photosensitizing Agents
oligonucleotides
inorganic peroxides
carbohydrates
biocompatibility
dendrites
versatility

All Science Journal Classification (ASJC) codes

  • Radiation
  • Radiological and Ultrasound Technology
  • Biophysics
  • Radiology Nuclear Medicine and imaging

Cite this

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title = "Cationic dendritic starch as a vehicle for photodynamic therapy and siRNA co-delivery",
abstract = "Cationic enzymatically synthesized glycogen (cESG) is a naturally-derived, nano-scale carbohydrate dendrite that has shown promise as a cellular delivery vehicle owing to its flexibility in chemical modifications, biocompatibility and relative low cost. In the present work, cESG was modified and evaluated as a vehicle for tetraphenylporphinesulfonate (TPPS) in order to improve cellular delivery of this photosensitizer and investigate the feasibility of co-delivery with short interfering ribonucleic acid (siRNA). TPPS was electrostatically condensed with cESG, resulting in a sub-50 nm particle with a positive zeta potential of approximately 5 mV. When tested in normal ovarian surface epithelial and ovarian clear cell carcinoma cell culture models, encapsulation of TPPS in cESG significantly improved cell death in response to light treatment compared to free drug alone. Dosages as low as 0.16 μM TPPS resulted in cellular death upon illumination with a 4.8 J/cm2 light dosage, decreasing viability by 96{\%}. cESG-TPPS was then further evaluated as a co-delivery system with siRNA for potential combination therapy, by charge-based condensation of an siRNA directed at reducing expression of manganese superoxide dismutase (Sod2) as a proof of principle target. Simultaneous delivery of TPPS and siRNA was achieved, reducing Sod2 protein expression to 48{\%}, while maintaining the photodynamic properties of TPPS under light exposure and maintaining low dark toxicity. This study demonstrates the versatility of cESG as a platform for dual delivery of small molecules and oligonucleotides, and the potential for further development of this system in combination therapy applications.",
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Cationic dendritic starch as a vehicle for photodynamic therapy and siRNA co-delivery. / Engelberth, Sarah A.; Hempel, Nadine; Bergkvist, Magnus.

In: Journal of Photochemistry and Photobiology B: Biology, Vol. 168, 01.03.2017, p. 185-192.

Research output: Contribution to journalArticle

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AU - Hempel, Nadine

AU - Bergkvist, Magnus

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