Ceramic-Based Nanoparticles Entrapping Water-Insoluble Photosensitizing Anticancer Drugs:  A Novel Drug−Carrier System for Photodynamic Therapy

Abstract

A novel nanoparticle-based drug carrier for photodynamic therapy is reported which can provide stable aqueous dispersion of hydrophobic photosensitizers, yet preserve the key step of photogeneration of singlet oxygen, necessary for photodynamic action. A multidisciplinary approach is utilized which involves (i) nanochemistry in micellar cavity to produce these carriers, (ii) spectroscopy to confirm singlet oxygen production, and (iii) in vitro studies using tumor cells to investigate drug-carrier uptake and destruction of cancer cells by photodynamic action. Ultrafine organically modified silica-based nanoparticles (diameter approximately 30 nm), entrapping water-insoluble photosensitizing anticancer drug 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide, have been synthesized in the nonpolar core of micelles by hydrolysis of triethoxyvinylsilane. The resulting drug-doped nanoparticles are spherical, highly monodispersed, and stable in aqueous system. The entrapped drug is more fluorescent in aqueous medium than the free drug, permitting use of fluorescence bioimaging studies. Irradiation of the photosensitizing drug entrapped in nanoparticles with light of suitable wavelength results in efficient generation of singlet oxygen, which is made possible by the inherent porosity of the nanoparticles. In vitro studies have demonstrated the active uptake of drug-doped nanoparticles into the cytosol of tumor cells. Significant damage to such impregnated tumor cells was observed upon irradiation with light of wavelength 650 nm. Thus, the potential of using ceramic-based nanoparticles as drug carriers for photodynamic therapy has been demonstrated.

Nanodrug applications in photodynamic therapy

“…These doped nanoagents were efficiently taken up by tumor cells in vitro and light irradiation resulted in significant cell death [59]. Similar results were reported for pheophorbide a-HSA (human serum albumin) nanoparticles [102].…”

“…PS can be modified by encapsulated them in delivery agents such as liposomes [54], micelles [55,56,57,58], ceramic based nanoparticles [59], gold nanoparticles [60,61], and polymer nanoparticles [62]. Liposomes, for example, are able to encapsulate hydrophobic as well as hydrophilic drugs.…”

“…Due to their small sizes they are not removed from the body by the RES system which leads to longer half-life times. They have a strong ability to protect encapsulated agents, are compatible with biological systems, and their surface can easily be modified with functional groups such as antibodies or other ligands to improve selectivity [38,59].…”

“…Examples of encapsulation of hydrophobic photosensitizers into nanomaterials are polymeric nanoparticles [88], e.g., a hydrophobic photosensitizer meso-tetra(phydroxyphenyl)porphyrin (m-THPP) encapsulated into polymeric nanoparticle poly(D,Llactide-co-glycolide) [89,90], dendrimer phthalocyanine (DPc)-encapsulated polymeric micelles (DPc/m) [32], polymeric protoporphyrin IX micelles [55], and organically modified silica-based nanoparticles [91] entrapping the photosensitizing anti-cancer drug 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide [59] have been used.…”

Chitosan-based nanogels for selective delivery of photosensitizers to macrophages and improved retention in and therapy of articular joints

“…In this context, nanosized polymeric composites/carriers may be of interest. Several strategies involving nanosized carriers for photosensitizer delivery such as liposomes, polymeric micelles, metal-based or silica-based nanoparticles have already been explored [15][16][17][18]. The preparation of chitosan-based hydrophilic nanogels has been widely described in the literature, employing penta sodium triphosphate (PSTP) as the complexing anionic molecule for the polycation chitosan [19][20][21][22][23][24][25].…”