Phthalocyanine-Conjugated Glyconanoparticles for Chemo-photodynamic Combination Therapy

Abstract

Combination cancer therapy based on multifunctional nanomaterials has attracted great attention. The present work focuses on the preparation of the glycopolymeric nanoparticle, which contains a photosensitizer (zinc(II)phthalocyanine, ZnPc) and an anticancer drug (Doxorubicin, Dox). First, a novel mono azide-functional ZnPc-N 3 with seven hydrophilic ethylene oxide chains was synthesized. Next, ZnPc alone or together with Dox bearing glycopolymers was synthesized via the RAFT polymerization method and then self-assembled into glyconanoparticles (GNPs) with narrow particle size distribution. Then the evaluation of the biological activity of GNPs (GNPs-ZnPc and GNPs-ZnPc/Dox) for dual photodynamic therapy (PDT) and chemotherapy against human breast cancer cells was investigated. The constructed GNPs were identified via general characterization methods, including dynamic light scattering (DLS) and transmission electron microscopy (TEM). The prepared GNPs-ZnPc/Dox demonstrated remarkable photophysical and photochemical properties, involving good colloidal stability in biological conditions, pH-responsive drug release, and the capacity to generate singlet oxygen under light irradiation. The outer layer of nanoparticles covered by fructose sugar moieties achieves a targeted cancer therapy owing to GLUT5 (a well-known fructose transporter) overexpression toward breast cancer cells. In vitro experiments were then performed to evaluate the chemo/phototoxicity, cellular uptake, and anticancer efficacy of GNPs-ZnPc/Dox. In comparison with free Dox, human breast cancer cells treated with GNPs-ZnPc/Dox exhibited a higher cellular internalization via GLUT5 targeting. In particular, the GNPs-ZnPc/Dox nanoplatform revealed an excellent synergistic anticancer activity in comparison with free ZnPc-N 3 and free Dox, representing a novel and promising chemophotodynamic combination therapeutic methodology to improve therapeutic efficacy.

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

“…178,179 Some nanoparticles were even used in combination with chemotherapeutic strategies, with the anticancer drugs soranefib 180 and doxorubicin. 181 This dual photo-and chemotherapeutic strategy has also been implemented with molecular complexes, with a histone deacetylase inhibitor 182 or with immunotherapeutic activity. 183 We can also cite a recent work on ZnPcs that target tumours through PEG functionalization.…”

Near-Infrared Fluorescent Micelles from Poly(norbornene) Brush Triblock Copolymers for Nanotheranostics

“…Polymeric micelles are fabricated rapidly from a large library of inexpensive starting materials and have tunable solubilization/dispersion properties to engineer in vivo performance. − The properties of such micellar assemblies are strongly dependent on the architecture of their corresponding polymeric building blocks and, ultimately, the method employed in their synthesis. A variety of amphiphilic block copolymers with unique architectures have been investigated for drug delivery applications, including linear block copolymers and complex architectures such as brush and star-like polymers. − …”

Tuning C-Phycocyanin Photoactivity via pH-Mediated Assembly–Disassembly

“…While the referenced cases demonstrate the potential photodynamic applications, the intrinsic photoactivity and tunability of phycobiliproteins, offered by their modular and flexible protein architecture, are overlooked and underutilized. Therefore, it is envisaged that with further development, the remarkable pH-responsiveness, photoactivity, and conformational flexibility of C-PC demonstrated in this work, along with this protein’s inherent biocompatibility and wide availability, will open new routes for its applications in cancer diagnosis, photodynamic therapy, drug delivery, and oxidation catalysis. − Our future work will be directed toward a series of application-centered studies based on the identified tunability and photoactivity of C-PC. First, in vivo and in vitro tests will be conducted to assess the intracellular uptake, therapeutic efficacy, and tumor cell selectivity of C-PC under pH controls.…”