Self-Assembled Nanophotosensitizing Systems with Zinc(II) Phthalocyanine-Peptide Conjugates as Building Blocks for Targeted Chemo-Photodynamic Therapy

Abstract

Two zinc­(II) phthalocyanines (ZnPcs) substituted with a short peptide (Gly-Gly-Lys) with either a carboxyl or a carbamoyl group at the C-terminus and an appended biotin moiety were prepared and characterized. They could self-assemble into spherical nanoparticles, namely ZnPc-GGK­(B)-COOH NP and ZnPc-GGK­(B)-CONH2 NP, through noncovalent interactions, which encapsulated the hydrophobic ZnPc units in the core and exposed the biotin moieties on the surface. The zeta potential of ZnPc-GGK­(B)-COOH NP in water was found to be −28 mV, whereas that of ZnPc-GGK­(B)-CONH2 NP was in opposite sign (+15 mV), reflecting the different functionality at the C-terminus, which also greatly affected the stability of the self-assembled nanoparticles. The targeting effect of ZnPc-GGK­(B)-COOH NP was examined against human hepatocellular carcinoma HepG2 cells, which overexpress biotin receptor, and Chinese Hamster Ovary CHO-K1 cells, which have a low expression of biotin receptor. This nanosystem was also coassembled with the chemotherapeutic doxorubicin (DOX) to form ZnPc-GGK­(B)-COOH/DOX NP. Both ZnPc-GGK­(B)-COOH NP and ZnPc-GGK­(B)-COOH/DOX NP could induce photocytotoxicity and apoptosis on HepG2 cells with an IC50 value of 1.48 and 0.49 μM ZnPc, respectively. For the latter nanosystem, the ZnPc and DOX components induced cytotoxicity in a synergistic manner. The photodynamic and chemotherapeutic effects of these two nanosystems were also examined on nude mice bearing a human colorectal adenocarcinoma HT29 tumor. The ZnPc-GGK­(B)-COOH/DOX NP exhibited a stronger tumor inhibition effect upon irradiation, demonstrating the presence of dual chemo-photodynamic therapeutic actions.

Ferric Ion Driven Assembly of Catalase‐like Supramolecular Photosensitizing Nanozymes for Combating Hypoxic Tumors

“…After studying this Fe 3+ ‐driven self‐assembling process, a photosensitizer was encapsulated into Fmoc‐Cys/Fe to form a nanophotosensitizing system. The carboxyl ZnPc [22] (Supporting Information, Figure S7) was chosen as the photosensitizer because of its strong absorption in the phototherapeutic window (650–800 nm), high singlet oxygen quantum yield, and readiness of undergoing self‐assembly with amino acids [23] . It was expected that the hydrophobic phthalocyanine ring and the hydrophilic carboxyl group of ZnPc could take part in the self‐assembly via hydrophobic interactions, π–π stacking, and electrostatic force.…”

“…Thec arboxyl ZnPc [22] (Supporting Information, Figure S7) was chosen as the photosensitizer because of its strong absorption in the phototherapeutic window (650-800 nm), high singlet oxygen quantum yield, and readiness of undergoing self-assembly with amino acids. [23] It was expected that the hydrophobic phtha-locyanine ring and the hydrophilic carboxyl group of ZnPc could take part in the self-assembly via hydrophobic interactions, p-p stacking, and electrostatic force.T he Fe 3+ ions inside the nanovesicles,l abeled as Fmoc-Cys/Fe@Pc, could catalyze the transformation of H 2 O 2 enriched in cancer cells to oxygen that can promote the photodynamic action and overcome the low oxygen level at hypoxic tumor. In addition, the HIF-1 inhibitor ACF(Supporting Information, Figure S7) was also encapsulated during the nanovesicle formation to form Fmoc-Cys/Fe@Pc/ACF,w hich could prolong its pharmacokinetic half-life and improve its tumor accumulation.…”

Self‐Assembled Binaphthyl‐Bridged Amphiphilic AABB Phthalocyanines: Nanostructures for Efficient Antimicrobial Photodynamic Therapy

“…In this regard, several nanostructured Pors have shown significant potential in phototheranostic applications [25–27] . Regarding Pc‐based systems, there are some reports describing the formation of nanoparticles [28] by self‐assembly from positively charged, A 3 B Zn II Pc [29, 30] and A 4 Zn II Pc [31] amphiphiles in water, which are used as PS systems for photodynamic and photothermal therapies.…”

“…Interestingly,t his approach avoids multistep fabrication of complex nano-delivery systems, and circumvents poor therapeutic outcomes associated to the low concentrationofd rug loading.I nthis regard, severalnanostructured Pors have shown significant potential in phototheranostic applications. [25][26][27] Regarding Pc-based systems, there are some reports describing the formation of nanoparticles [28] by self-assembly from positively charged, A 3 BZ n II Pc [29,30] and A 4 Zn II Pc [31] amphiphiles in water,which are used as PS systems for photodynamic and photothermal therapies.…”

Peptide-Tetrapyrrole Supramolecular Self-Assemblies: State of the Art

“…The presence of biotin in conjugates 52a , b can direct the PDT action of self-assembled nanospheres to target cells overexpressing biotin receptor [ 112 ]. Complex 52a can also co-assemble with the chemotherapeutic agent doxorubicin to form spherical nanoparticles that induce apoptosis in a synergistic manner and have a strong tumor inhibition effect upon irradiation in vitro and in vivo.…”