Porphyrin‐based bridged silsesquioxane nanoparticles for targeted two‐photon photodynamic therapy of zebrafish xenografted with human tumor

Abstract

Background: Bridged silsesquioxane nanoparticles (BSNs) recently described represent a new class of nanoparticles exhibiting versatile applications and particularly a strong potential for nanomedicine. Aims:In this work, we describe the synthesis of BSNs from an octasilylated functional porphyrin precursor (PORBSNs) efficiently obtained through a click reaction. These innovative and very small-sized nanoparticles were functionalized with PEG and mannose (PORBSNs-mannose) in order to target breast tumors in vivo. Methods and Results:The structure of these nanoparticles is constituted of porphyrins J aggregates that allow two-photon spatiotemporal excitation of the nanoparticles. The therapeutic potential of such photoactivable nanoparticles was first studied in vitro, in human breast cancer cells in culture and then in vivo on zebrafish embryos bearing human tumors. These animal models were intravenously injected with 5 nL of a solution containing PORBSNs-mannose. An hour and half after the injection of photoactivable and targeted nanoparticles, the tumor areas were excited for few seconds with a two-photon beam induced focused laser. We observed strong tumor size decrease, with the involvement of apoptosis pathway activation. Conclusion:We demonstrated the high targeting, imaging, and therapeutic potential of PORBSNs-mannose injected in the blood stream of zebrafish xenografted with human tumors. KEYWORDSbridged silsesquioxane nanoparticles, human tumor targeting, photodynamic therapy, two-photon excitation Soraya Dib and Dina Aggad contribute equally to this work.

Porphyrin‐Based Nanoparticles: A Promising Phototherapy Platform

“…The porphyrin-doped peptide nanoparticles had the high 1 O 2 production and effectively induce MCF-7 cells ablation under two-photon irradiation. Dib et al [96] prepared porphyrin-based bridged siloxane nanoparticles (PORBSNs) by click reaction using octaalkyl porphyrins as photosensitizers. PORBSNs were further modified with polyethylene glycol (PEG) groups and mannose groups to enhance their water solubility and ability to target breast cancer cells.…”

“…Porphyrin-based nanoparticles with water-soluble PX SNP [35] HCT-116, HAT-29 Tcpp-CDs [39] EC109 UCNP-PJ [40] LS180 TPP-GA NPs [44] HeLa, HepG2 and K1 TPP-PPh 3 -4PEG NPs [45] 4T1 Porphyrin-based nanoparticles with high reactive oxygen production capacity TPPS4@PMMA-NPs [48] HepG2 Na-ZnTCPP-1•GNP [49] MCF-10A, SKBR-3 ZnTPP@SiO 2 [52] HaLa ZnDTPP-I 2 �UiO-66 [57] HepG2 UiO-66-TPP-SH [58] HaLa Porphyrin-based nanoparticles for target overexpressed receptors PR-AuNP-PEG-ab nanoparticles [60] SK-BR-3 Fe 3 O 4 @mSiO 2 (TPPS)-PL [63] HepG2 Folate-Porphysome [64] KB, HT1080 FPs [65] A549, SBC5 Tumor microenvironment-responsive UIO@Ca-Pt [75] CT26 FT@HA NPs [83] 4T1 AuNPsDOX/PtTPyP@-ZIF-8 [86] HeLa g-C 3 N 4 -P2 [87] HeLa, T24 and MRC-5 Porphyrin-based nanoparticles for two-photon excited photodynamic therapy porphyrin-doped peptide nanoparticles [96] MCF-7 PORBSNs-mannose [97] MDA-MB-231 PMO-AMFA [98] RMS-YM Porphyrin-based nanoparticles for chemo-photodynamic combination therapy PEG-Por-CD: oxliPt (IV)-ada [105] 4T1 PS1-EPMOs, PS2-EPMOs [107] MCF-7 DOX@TPP-PEG-biotin SANs [109] MOFs@MnO 2 [110] HaLa ChemPlusChem provide the direction and impetus for the development of efficient and low-toxicity PDT nanotherapeutics, and promote the development of tumor-targeted therapy. More importantly, these porphyrin-based nanoparticles can effectively combine photodynamic therapy with two-photon therapy or chemotherapy, and the resulting combined therapeutic effect has a 1 + 1 > 2 therapeutic effect.…”

“…Porphyrin-based nanoparticles have been successfully applied in two-photon photodynamic therapy (TP-PDT), [96][97][98] surprisingly, Li et al [171] successfully prepared a near-infrared fluorescence imaging-guided TP-PDT therapeutic agent (AuNR@ SiO 2 -TPP(8%)/PFV NPs). Under dark conditions, AuNR@SiO 2 -TPP(8%)/PFV NPs produced almost no toxicity thereby leading to a 100% survival rate of HeLa cells.…”

Zebrafish Models for the Safety and Therapeutic Testing of Nanoparticles with a Focus on Macrophages

“…Similarly, small-seized non-porous porphyrin-based bridged silsesquioxane NPs (PORBSNs) functionalized with PEG and mannose (20–30 nm) were developed for i.v. injection and tested in zebrafish with MDA-MB-231-GFP cells subjected to TPE-PDT, showing decreased tumor growth after irradiation [ 132 ]. Moreover, with targeting purposes, Peng et al synthesized fluorescent cellulose acetate NPs functionalized with folate groups for their preferential accumulation in epithelial cancer cells overexpressing folic acid receptors [ 140 ].…”

Zebrafish as a Model for Anticancer Nanomedicine Studies

“…Then the particles were intravenously injected into the 4 dpf zebrafish model that bearing the human breast tumor. After one and half hours the tumor areas were excited with a two-photon beam-induced focused laser and this results in a strong reduction in the tumor size and activation of apoptosis pathways [ 147 ]. No toxicity has been seen on the xenografted zebrafish embryos after NPs injection [ 147 ] ( Table 1 ).…”