Nanoscopic micelle delivery improves the photophysical properties and efficacy of photodynamic therapy of protoporphyrin IX

Abstract

Nanodelivery systems have shown considerable promise in increasing the solubility and delivery efficiency of hydrophobic photosensitizers for photodynamic therapy (PDT) applications. In this study, we report the preparation and characterization of polymeric micelles that incorporate protoporphyrin IX (PpIX), a potent photosensitizer, using non-covalent encapsulation and covalent conjugation methods. Depending on the incorporation method and PpIX loading percentage, PpIX existed as a monomer, dimer or aggregate in the micelle core. The PpIX state directly affected the fluorescence intensity and 1 O 2 generation efficiency of the resulting micelles in aqueous solution. Micelles with lower PpIX loading density (e.g. 0.2%) showed brighter fluorescence and higher 1 O 2 yield than those with higher PpIX loading density (e.g. 4%) in solution. However, PDT efficacy in H2009 lung cancer cells showed an opposite trend. In particular, 4% PpIX-conjugated micelles demonstrated the largest PDT therapeutic window, as indicated by the highest phototoxicity and relatively low dark toxicity. Results from this study contribute to the fundamental understanding of nanoscopic structure-property relationships of micelle-delivered PpIX and establish a viable micelle formulation (i.e. 4% PpIX-conjugated micelles) for in vivo evaluation of antitumor efficacy.

Treating cutaneous squamous cell carcinoma using 5-aminolevulinic acid polylactic-co-glycolic acid nanoparticle-mediated photodynamic therapy in a mouse model

“…2 Although ALA PDT shows some promise for the treatment of superficial SCC, 3 it is not currently recommended for the treatment of invasive SCC, mainly due to the limited bioavailability of ALA in the skin tissue. 4,5 Nanoparticles (NPs) might be a useful approach for delivering ALA in topical PDT, since NPs might improve ALA stability and cutaneous penetration. 6 An NP-delivery system might also improve the selective accumulation of photosensitizer in the diseased tissue.…”

In vitro evaluation of 5-aminolevulinic acid (ALA) loaded PLGA nanoparticles

“…Although ALA-PDT shows some promise for the treatment of superficial SCC, 6 currently, it is not recommended for the treatment of invasive SCC mainly because (1) the local bioavailability of ALA is insufficient for a complete therapeutic effect, despite the fact that ALA can permeate the skin barrier, (2) ALA is unstable in physiological environments, and (3) diffusion of ALA through cell membranes is limited due to its polarity. 7,8 Several studies suggest that nanoparticle (NP) drug delivery systems (eg, liposomes, chitosan NPs, gold NPs) might be useful for overcoming these deficiencies and enhance the effectiveness of topical ALA-PDT. [9][10][11] But these NP systems have some drawbacks such as instability, leakage of encapsulated drug, and unknown long-term side effects.…”

“…Several methods have been suggested for improving ALA transdermal delivery, which include microneedles, patch-based systems, microemulsions, iontophoresis, and laser. 7,[20][21][22] Extensive research has also been carried out to develop NP drug delivery systems for ALA, [8][9][10][11] but PLGA NPs have not been tested for ALA delivery before.…”

5-aminolevulinic acid-incorporated nanoparticles of methoxy poly(ethylene glycol)-chitosan copolymer for photodynamic therapy

“…[17][18][19][20] Among them, nanoscopic vehicles such as polymeric micelles and nanoparticles have been investigated as ideal carriers for drugs, including photosensitizers. [20][21][22] Nanoparticles are regarded as ideal vehicles for targeting solid tumors, because of their favorable biodistribution, excellent bioavailability, and reduction of the intrinsic toxicity of the drugs. [22][23][24] In this study, we prepared 5-ALA-incorporated nanoparticles using methoxy poly(ethylene glycol)/chitosan (PEGChito) copolymer, and their photodynamic potential was tested using CT26 colorectal carcinoma cells.…”