Self-assembled liposomal nanoparticles in photodynamic therapy

Abstract

Photodynamic therapy (PDT) employs the combination of non-toxic photosensitizers (PS) together with harmless visible light of the appropriate wavelength to produce reactive oxygen species that kill unwanted cells. Because many PS are hydrophobic molecules prone to aggregation, numerous drug delivery vehicles have been tested to solubilize these molecules, render them biocompatible and enhance the ease of administration after intravenous injection. The recent rise in nanotechnology has markedly expanded the range of these nanoparticulate delivery vehicles beyond the well-established liposomes and micelles. Self-assembled nanoparticles are formed by judicious choice of monomer building blocks that spontaneously form a well-oriented 3-dimensional structure that incorporates the PS when subjected to the appropriate conditions. This self-assembly process is governed by a subtle interplay of forces on the molecular level. This review will cover the state of the art in the preparation and use of self-assembled liposomal nanoparticles within the context of PDT.

Keywords: liposomes; nanoparticles; nanotechnology; photodynamic therapy; self-assembly.

Figure 1. Jablonski diagram

Initial absorption of a photon by the ground state of the PS gives rise to the short-lived excited singlet state. This state can lose energy by fluorescence, internal conversion to heat, or by intersystem crossing to the long-lived triplet state. PS triplet states are efficiently quenched by energy transfer to molecular oxygen (a triplet state) to give singlet oxygen (Type 2) or by electron transfer to oxygen or to biomolecules to give superoxide and hydroxyl radical (Type 1).

Figure 2. Representative chemical structures of PS that have been used in combination with nanoparticles

(A) Chlorin(e6) (ce6), (B) Benzoporphyrin derivative (BPD), (C) Zinc phthalocyanine (ZnPC), (D) m-Tetra(hydroxyphenyl)chlorin (mTHPC), (E) Aluminum phthalocyanine tetrasulfonate (AlPcS4).

Figure 3. PS encapsulated in liposomes by localizing in different domains

Water-soluble molecules or solid molecules can be loaded in the internal aqueous (hydrophilic core); amphiphilic molecules orient into liposomal bilayer (hydrophobic core); transmenbrane proteins span the lipid bilayer with sites exposed to the aqueous phase.