Monomer zinc phthalocyanine/upconversion nanoparticle coated with hyaluronic acid crosslinked gel as NIR light-activated drug for in vitro photodynamic therapy

Abstract

Carboxyl group modified zinc phthalocyanines (ZnPc) are classic and widely used photosensitizers (PSs) in upconversion nanoparticles (UCNPs) mediated photodynamic therapy (PDT) for tumor treatment. To improve the PDT activity of the complex system of ZnPc and UCNPs, many UCNPs with high red emission intensity were design and prepared. ZnPc-(COOH) tends to aggregate both in water and under physiological conditions, which can sharply decrease its PDT activity. Therefore, choosing monomeric COOH groups modified ZnPc as PSs is an alternative way to improve their activity. In this manuscript, three zinc(ii) phthalocyanines, substituted with 4 (ZnPc-(COOH)), 8 (ZnPc-(COOH)) and 16 (ZnPc-(COOH)) COOH groups, were synthesized. A comparison of the results indicated that ZnPc-(COOH) existed in its monomeric form under physiological conditions because of its large substituents. Moreover, ZnPc-(COOH) showed superior singlet oxygen (O) generation ability when compared to ZnPc-(COOH) and ZnPc-(COOH). Therefore, we chose ZnPc-(COOH) as PSs for absorption on the surface of the UCNPs. Then, they were encapsulated by crosslinked methacrylated hyaluronic acid (m-HA), which provides active tumor accumulation ability by binding its overexpressed receptors on the surface of cancer cells. The resulting nanoparticles can be effectively taken up by cancer cells and shows strong near-infrared (NIR) light triggered PDT in vitro.

Recent Advances in Photo-Crosslinkable Hydrogels for Biomedical Applications

“…For example, HA is a natural ligand to hyaluronan receptor (e.g.,CD44), which is overexpressed in various types of tumors, suggesting its great potential in drug delivery and cancer therapy [108]. UV light-crosslinked MeHA hydrogel was incorporated with upconversion nanoparticles to deliver carboxyl group-modified zinc phthalocyanines (a photosensitizer), which can generate an abundance of singlet oxygen upon activation using near-infrared light to kill gastric cancer cells [109]. MeHA hydrogel was also incorporated with drug-loaded mesoporous silica nanoparticles (a sonosensitizer) to achieve a chemotherapy-sonodynamic therapy for the treatment of breast cancer [101] (Figure 4A).…”

Phototherapeutic anticancer strategies with first-row transition metal complexes: a critical review

“…To prevent this, several techniques were developed, such as, for example, the incorporation of a charged moiety: either positive 144–148 or negative. 149,150 ZnPcs can also be encapsulated in cyclodextrins, 151 liposomes, 152–154 micelles, 155–158 or nanoparticles (that can consist of polymers, 159–161 silica, 162,163 gold, 164,165 or TiO 2 166 ). Two ZnPcs were or are already in phase II clinical trials: CGP55847, which is a liposomal formulation of ZnPc, used against squamous cell carcinomas, 167 and photocyanine, a di-(potassium sulfonate)-di-phthalimidomethyl ZnPc which was under clinical trial in China against human hepatocellular carcinoma up to phase II (Fig.…”

“…To prevent this, several techniques were developed, such as, for example, the incorporation of a charged moiety: either positive [144][145][146][147][148] or negative. 149,150 ZnPcs can also be encapsulated in cyclodextrins, 151 liposomes, [152][153][154] micelles, [155][156][157][158] or Fig. 16 Phototoxic zinc phthalocyanine complexes.…”

Upconversion in photodynamic therapy: plumbing the depths

“…Hyaluronic acid is another ligand used for active targeting, that recognizes cluster-determinant 44 (CD44), which is overexpressed on many cancer types and also on cancer stem cells 63 . Hyaluronic acid has been used for active targeting of UCNPs by several groups 42, 64–66 . RGD (arginine-glycine-aspartate) is a 3-amino acid motif that is usually incorporated into a cyclic peptide, and which recognizes the alpha V beta 3 integrin (and several other integrins) that are overexpressed on cancer cells and cancer-associated neovascular endothelial cells 67, 68 .…”