Synthesis and Aggregation of a Porphyrin-Cored Hyperbranched Polyglycidol and Its Application as a Macromolecular Photosensitizer for Photodynamic Therapy

Abstract

Macromolecules are potentially useful delivery systems for cancer drugs as their size allows them to utilize the enhanced permeability and retention effect (EPR), which facilitates selective delivery to (and retention within) tumors. In addition, macromolecular delivery systems can prolong circulation times as well as protecting and solubilizing toxic and hydrophobic drug moieties. Overall these properties and abilities can result in an enhanced therapeutic effect. Photodynamic therapy (PDT) combines the use of oxygen and a photosensitizer (PS), that become toxic upon light-irradiation. We proposed that a PS encapsulated within a water-soluble macromolecule could exploit the EPR effect and safely and selectively deliver the PS to a tumor. In this paper, we describe the synthesis of a porphyrin cored hyperbranched polymer that aggregated into larger micellar structures. DLS and TEM indicated that these aggregated structures had diameters of 45 nm and 20 nm for the solvated and non-solvated species respectively. The porphyrin cored HBP (PC-HBP), along with the non-encapsulated porphyrin (THPP), were screened against EJ bladder carcinoma cells in the dark and light. Both THPP and PC-HBP displayed good toxicity in the light, with LD50 concentrations of 0.5 M and 1.7 M respectively. However, in the dark, the non-incorporated porphyrin (THPP) displayed significant toxicity, generating an LD50 of 4 M. On the other hand, no dark toxicity was observed for the polymer system (PC-HBP) at concentrations of 100 M or less. As such, incorporation within the large polymer aggregate serves to eliminate dark toxicity, whilst maintaining excellent toxicity when irradiated.

pH-Responsive Pluronic F127–Lenvatinib-Encapsulated Halogenated Boron-Dipyrromethene Nanoparticles for Combined Photodynamic Therapy and Chemotherapy of Liver Cancer

“… 11 , 12 Phototherapy, including photodynamic therapy (PDT) is a new method for the treatment of cancer. 13 , 14 It can trigger a series of photochemical and photobiological reactions under specific wavelength laser irradiation by a photosensitizer, 15 the most important of which is the production of reactive oxygen species (ROS, such as singlet oxygen 1 O 2 , superoxide anion radical O 2 • – , and hydroxyl radical •HO), 16 − 18 thereby killing tumor cells. Boron-dipyrromethene (BODIPY) as a fluorescent dye is widely used in PDT due to its efficient singlet oxygen yield and gentle synthesis process.…”

Hyaluronic Acid-Conjugated with Hyperbranched Chlorin e6 Using Disulfide Linkage and Its Nanophotosensitizer for Enhanced Photodynamic Therapy of Cancer Cells

“…Since nanomedicines, such as nanoparticles, polymeric micelles, and nanomaterials, have unique properties, such as large surface area, long blood circulation with avoidance of reticuloendothelial (RES) organ uptake, passive/active targeting efficiency against cancer cells, and solubilization of hydrophobic drugs, they possess advantages for the targeting of tumor microenvironment [18,40,41,42,43,44,45]. Among various nanomaterials, hyperbranched polymer materials, such as dendrimer, are spotlighted as a drug-delivery carrier because they possess unique properties, such as lower viscosity, intrinsic molecular behavior, and a lower hydrated radius [45,46,47]. Furthermore, dendrimers have many functional groups for modification with anticancer drugs and targeting moiety [45].…”

“…We previously reported that dendrimer nanoparticles significantly improve the intracellular delivery of doxorubicin, overcomes multi-drug resistance and targets solid tumor specifically [45]. Kadhim et al, reported that porphyrin-cored hyperbranched polymers displayed good PDT-induced toxicity against bladder carcinoma cells with no dark toxicity, while porphyrin itself showed significant dark toxicity [47]. Furthermore, Yang et al, also reported that Ce6-incorporated polyethyleneimine nanoparticles have superior PDT efficacy and intracellular delivery capacity [21].…”

“…There is no report for the branched Ce6 material anywhere as far as we know. Most of the nano-scale photosensitizers are related to simple branched polymers, linear polymers, and nanomaterials [15,18,21,39,47]. The higher Ce6 uptake ratio in the cancer cells was observed with Ce6tetraHA or Ce6decaHA nanophotosensitizers with negligible dark cytotoxicity (Figure 6).…”

Amphiphilic drug–peptide–polymer conjugates based on poly(ethylene glycol) and hyperbranched polyglycerol for epidermal growth factor receptor targeting: the effect of conjugate aggregation on in vitro activity

“…hyperbranched polyglycerol (HbPG), are intensively investigated as biocompatible nanocarriers. [21][22][23][24][25][26][27][28] HbPG has outstanding water solubility and biocompatibility; furthermore its synthesis and functionalization can be performed easily. 29 Moreover, procedures to produce HbPGs by conjugation of relevant functionalities, such as amine, carboxylic, chloroacetamide and maleimide in well-defined numbers and positions, have already been developed.…”