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Polymeric Photosensitizer Nanocomplex Encapsulated T-lymphocyte Delivery System for Photodynamic Therapy of Cancer
mTHPP or 5,10,15,20-Tetrakis (3-hydroxyphenyl) porphyrine is a best suited model anticancer drug for mTHPC or m-tetra (hydroxy) phenyl chlorin which is used as a second generation photosensitizer in photodynamic therapy (Chatterjee et al, 2008). Though, mTHPP is an effective anticancer drug, suffers...
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| Format: | Dissertation |
| Sprache: | Englisch |
| Veröffentlicht: |
Philipps-Universität Marburg
2017
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| Zusammenfassung: | mTHPP or 5,10,15,20-Tetrakis (3-hydroxyphenyl) porphyrine is a best suited model anticancer drug for mTHPC or m-tetra (hydroxy) phenyl chlorin which is used as a second generation photosensitizer in photodynamic therapy (Chatterjee et al, 2008). Though, mTHPP is an effective anticancer drug, suffers from biopharmaceutical and physiological limitations. The problem pertaining to formulation development arises due to very low aqueous solubility (Konan et al, 2002) and tendency of mTHPP to accumulate in cell membrane from where it slowly releases and degrades (Ochsner et al, 1997). These hurdles can be effectively circumvented by designing nanoparticles but targeting cancerous cells through these nanocarriers still remains a major challenge. Due to presence of T cell receptors on cancerous cells, they acquire the ability to recognise and attack cancerous cells and make a tumor targeting autoimmune machinery. This autoimmune mechanism can be exploited to develop an immune cell (T cell) based delivery system by loading mTHPP (as nanocomplex) into T cells. Such safe homing of mTHPP into T cell is capable of selective delivery and targeting cancer cells as well as avoiding numerous side effects associated with mTHPP while present in blood.
mTHPP binds with each polymer viz, polystyrene sulphonate Na, polyvinylpyrrolidone and Chitosan hydrochloride (Protasan®) through non-covalent bondings. These physical bonds are weak therefore facilitates release of drug. Interestingly, these nanocomplexes also possess fluorescence, thus acting as an ideal carrier for mTHPP for photodynamic therapy. Polymeric nanocomplexes of mTHPP (PNC) are internalized into Jurkat cell (JC) by electroporation because this is simple, time saving and economic method of intracellular delivery. PNC loaded JCs form an immune cell based delivery system which is intended to be administered directly into blood following identification and binding with cancer cells. Exposure of cancer affected area with suitable wavelength of light leads to excitation of PNC and generation of ROS (Reactive oxygen species) which kill surrounding cancer cells including Jurkat cells.
PNC were characterized by UV spectroscopy to confirm formation of mTHPP-polymer NC while keeping fluorescence property intact which is prerequisite for photodynamic activity. Characterization by AFM revealed morphology and particle size of PNC between 10-80 nm which is smaller enough for effective intracellular delivery. Analytical methods by UV and fluorescence spectroscopies were developed for quantification of mTHPP.
Thus, a proof of concept was designed pertaining to enhancement of aqueous solubility of mTHPC by complexation with different polymers and development of its T lymphocyte based delivery system for photoimmunotherapy of cancer using mTHPP as a model drug for mTHPC and JCs as model cell for T lymphocytes respectively. |
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| Umfang: | 108 Seiten |
| DOI: | 10.17192/z2017.0217 |