Novel methods to incorporate photosensitizers into nanocarriers for cancer treatment by photodynamic therapy
✍ Scribed by Shouyan Wang; Wenzhe Fan; Gwangseong Kim; Hoe Jin Hah; Yong-Eun Koo Lee; Raoul Kopelman; Manivannan Ethirajan; Anurag Gupta; Lalit N. Goswami; Paula Pera; Janet Morgan; Ravindra K. Pandey
- Book ID
- 102932708
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 820 KB
- Volume
- 43
- Category
- Article
- ISSN
- 0196-8092
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✦ Synopsis
Objective: A hydrophobic photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), was loaded into nontoxic biodegradable amine functionalized polyacrylamide (AFPAA) nanoparticles using three different methods (encapsulation, conjugation, and post-loading), forming a stable aqueous dispersion. Each formulation was characterized for physicochemical properties as well as for photodynamic performance so as to determine the most effective nanocarrier formulation containing HPPH for photodynamic therapy (PDT). Materials and Methods: HPPH or HPPH-linked acrylamide was added into monomer mixture and polymerized in a microemulsion for encapsulation and conjugation, respectively. For post-loading, HPPH was added to an aqueous suspension of pre-formed nanoparticles. Those nanoparticles were tested for optical characteristics, dye loading, dye leaching, particle size, singlet oxygen production, dark toxicity, in vitro photodynamic cell killing, whole body fluorescence imaging and in vivo PDT. Results: HPPH was successfully encapsulated, conjugated or post-loaded into the AFPAA nanoparticles. The resultant nanoparticles were spherical with a mean diameter of 29 AE 3 nm. The HPPH remained intact after entrapment and the HPPH leaching out of nanoparticles was negligible for all three formulations. The highest singlet oxygen production was achieved by the postloaded formulation, which caused the highest phototoxicity in in vitro assays. No dark toxicity was observed. Post-loaded HPPH AFPAA nanoparticles were localized to tumors in a mouse colon carcinoma model, enabling fluorescence imaging, and producing a similar photodynamic tumor response to that of free HPPH in equivalent dose. Conclusions: Post-loading is the promising method for loading nanoparticles with hydrophobic photosensitizers to achieve effective in vitro and in vivo PDT. Lasers Surg.