Jiacheng Zhao

A new role of curcumin: as a multicolor photoinitiator for polymer fabrication under household UV to red LED bulbs

Curcumin exhibits broad ground state light absorption and can act as a photoinitiator for the free radical photopolymerization of methacrylates under air upon exposure to different household LED bulbs. The effects of temperature and various additives on the photoinitiation efficiency of curcumin-based systems have been investigated. The curcumin-based system exhibits the highest photoinitiation efficiency at 25 °C. Additives also play an important role in the photoinitiation efficiency, and well-designed systems can even demonstrate higher efficiency than the commercial type I photoinitiator [phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (XBPO)] and type II photoinitiator [camphorquinone (CQ)]. Interestingly, the curcumin/diphenyliodonium hexafluorophosphate/triphenylphosphine combination is a capable multicolor photoinitiating system able to initiate free radical photopolymerization under air upon exposure to UV, blue, green, yellow, red, and warm white household LED bulbs. In addition, reversible addition–fragmentation chain transfer (RAFT) photopolymerization of N-isopropylacrylamide can also be achieved using a curcumin-based system under the irradiation of a blue LED bulb. The photochemical mechanisms associated with the generation of radicals from the investigated photoinitiating systems are investigated by different techniques (fluorescence, steady state photolysis, and electron spin resonance spin-trapping methods) and discussed in detail. More interestingly, the polymer sample produced through the photopolymerization process using the curcumin-based photoinitiating system demonstrates almost no toxicity to human fibroblast Hs-27 cells, endowing this photoinitiating system with great potential for the fabrication of biocompatible polymeric materials.

Cellular Uptake and Movement in 2D and 3D Multicellular Breast Cancer Models of Fructose-Based Cylindrical Micelles That Is Dependent on the Rod Length

While the shape effect of nanoparticles on cellular uptake has been frequently studied, no consistent conclusions are available currently. The controversy mainly focuses on the cellular uptake of elongated (i.e., filaments or rod-like micelles) as compared to spherical (i.e., micelles and vesicles) nanoparticles. So far, there is no clear trend that proposes the superiority of spherical or nonspherical nanoparticles with conflicting reports available in the literature. One of the reasons is that these few reports available deal with nanoparticles of different shapes, surface chemistries, stabilities, and aspects ratios. Here, we investigated the effect of the aspect ratio of cylindrical micelles on the cellular uptake by breast cancer cell lines MCF-7 and MDA-MB-231. Cylindrical micelles, also coined rod-like micelles, of various length were prepared using fructose-based block copolymers poly(1-O-methacryloyl-β-d-fructopyranose)-b-poly(methyl methacrylate). The critical water content, temperature, and stirring rate that trigger the morphological transition from spheres to rods of various aspect ratios were identified, allowing the generation of different kinetically trapping morphologies. High shear force as they are found with high stirring rates was observed to inhibit the formation of long rods. Rod-like micelles with length of 500-2000 nm were subsequently investigated toward their ability to translocate in breast cancer cells and penetrate into MCF-7 multicellular spheroid models. It was found that shorter rods were taken up at a higher rate than longer rods.

Carbohydrate-Specific Uptake of Fucosylated Polymeric Micelles by Different Cancer Cell Lines

Inspired by upregulated levels of fucosylated proteins on the surfaces of multiple types of cancer cells, micelles carrying β-l-fucose and β-d-glucose were prepared. A range of block copolymers were synthesized by reacting a mixture of 2-azidoethyl β-l-fucopyranoside (FucEtN3) and 2-azideoethyl β-d-glucopyranoside (GlcEtN3) with poly(propargyl methacrylate)-block-poly(n-butyl acrylate) (PPMA-b-PBA) using copper-catalyzed azide-alkyne cycloaddition (CuAAC). Five block copolymers were obtained ranging from 100 mol % fucose to 100% glucose functionalization. The resulting micelles had hydrodynamic diameters of around 30 nm. In this work, we show that fucosylated micelles reveal an increased uptake by pancreatic, lung, and ovarian carcinoma cell lines, whereas the uptake by the healthy cell lines (CHO) is negligible. This finding suggests that these micelles can be used for targeted drug delivery toward cancer cells.

N‐Vinylcarbazole as Versatile Photoinaddimer of Photopolymerization under Household UV LED Bulb (392 nm)

N-vinylcarbazole (NVK) can act simultaneously as a photoinitiator, an additive, and a mono-mer (photoinaddimer) of photopolymerization upon exposure to the household ultraviolet (UV) light-emitting diode (LED) bulb (emission wavelength centered at 392 nm). Even though the light absorption spectrum of NVK exhibits weak overlapping with the emission spectrum of the UV LED, the active species (i.e., radicals and cations) can be generated from the interaction between NVK and diphenyliodonium hexafluorophosphate (Iod) under irradiation of this LED device, which is investigated by steady state photolysis and electron spin resonance spin-trapping methods. Interestingly, the generated radicals and cations from the NVK/Iod system demonstrate high efficiency to initiate the free radical photopolymerization of (meth)acrylates and the cationic photopolymerization of epoxide and divinyl ether under the UV LED irradiation, and the one-step simultaneous catonic/radical photopolymerization of expoxide/acrylate blend can lead to the formation of tack free polyacrylate/polyether-based interpenetrated polymer network film within 10 min even when the polymerization process is exposed to the atmosphere highlighting the high efficiency of the system to reduce the oxygen inhibition effect. More interestingly, NVK/Iod system can also initiate the photopolymerization of NVK under the UV LED irradiation to produce polyvinylcarbazole, and NVK acts as both a photoinitiator and a monomer in the system.

Influence of nanoparticle shapes on cellular uptake of paclitaxel loaded nanoparticles in 2D and 3D cancer models

Enhanced cellular uptake and efficient penetration of nanocarriers inside tumors is paramount to successful anti-cancer therapy. While many studies have shown the important role nanoparticle shape plays in cellular uptake, no detailed conclusions on the most efficient drug carrier shape have been drawn at this stage. Here, a series of fructose-based amphiphilic block copolymers poly(1-O-MAFru)-b-PMMA are synthesized via RAFT polymerization. Three different morphologies (spheres, rods and vesicles) are prepared by self-assembly under different processing conditions. The shape effects of fructose-coated nanoparticles on cellular uptake by two breast cancer cell lines (MCF-7 cells and MDA-MB-231 cells) in 2D and 3D cell culture models are investigated. The cytotoxicity of corresponding paclitaxel-loaded nanoparticles are tested as well to give a comprehensive comparison between cellular uptake and resulting therapeutic efficacy after drug encapsulation in both cell culture models. Consistent results in 2D models confirm the shape effect of nanoparticles on cellular uptake. Unexpectedly, the shape does influence significantly the cell growth inhibition in 3D multicellular spheroids due to the possible cessation of transcellular delivery of nanoparticles in the apoptotic peripheral cells, caused by faster release of drugs from un-crosslinked micelles. Our results confirm the shape effect of nanoparticles on 2D models can vary from 3D models due to parameters such as spheroid penetration that can now play a pivotal role.

Entry of nanoparticles into cells: the importance of nanoparticle properties

Knowledge of the interactions between nanoparticles (NPs) and cell membranes is of great importance for the design of safe and efficient nanomedicines. Extensive studies aimed at understanding the correlation of NP properties with endocytosis have been carried out in the past few years. Here, we review the recent progress of these studies and provide an overview of the current state of knowledge on the influence of NP size, shape, stiffness and surface chemistry on cellular uptake. Special attention was dedicated to the uptake of non-spherical nanoparticles. Some general principles obtained from these fundamental studies will serve as guidelines for the design of optimised NP for enhanced cellular uptake. Finally, the opportunities for polymer chemists are discussed.

PEG Grafted‐Nanodiamonds for the Delivery of Gemcitabine

Carboxyl end-functionalized poly[poly(ethylene glycol) methyl ether methacrylate] [P(PEGMEMA)] and its block copolymer with gemcitabine substituted poly(N-hydroxysuccinimide methacrylate) [PGem-block-P(PEGMEMA)] are synthesized via reversible addition-fragmentation transfer (RAFT) polymerization. Then, two polymers are grafted onto the surface of amine-functionalized nanodiamonds to obtain [P(PEGMEMA)]-grafted nanodiamonds (ND-PEG) and [PGem-block-P(PEGMEMA)]-grafted nanodiamonds (ND-PF). Gemcitabine is physically absorbed to ND-PEG to produce ND-PEG (Gem). Two polymer-grafted nanodiamonds (i.e., with physically absorbed gemcitabine ND-PEG (Gem) and with chemically conjugated gemcitabine ND-PF) are characterized using attenuated total reflectance infrared spectroscopy, dynamic light scattering, and thermogravimetric analysis. The drug release, cytotoxicity (to seed human pancreatic carcinoma AsPC-1 cells), and cellular uptake of ND-PEG (Gem) and ND-PF are also investigated.

Dihydroxyanthraquinone derivatives: natural dyes as blue-light-sensitive versatile photoinitiators of photopolymerization

Four dihydroxyanthraquinone derivatives [i.e. 1,2-dihydroxyanthraquinone (12-DHAQ), 1,4-dihydroxyanthraquinone (14-DHAQ), 1,5-dihydroxyanthraquinone (15-DHAQ), and 1,8-dihydroxyanthraquinone (18-DHAQ)], when combined with various additives (e.g. iodonium salt, tertiary amine, N-vinylcarbazole, phenacyl bromide, and 4-cyanopentanoic acid dithiobenzoate), are investigated as photoinitiating systems for free radical photopolymerization [e.g. cross-linked free radical photopolymerization of multifunctional monomers or reversible addition–fragmentation chain transfer (RAFT) photopolymerization of monofunctional monomers] and cationic photopolymerization. 14-DHAQ, 15-DHAQ and 18-DHAQ exhibit good solubility in solvent (acetonitrile) and monomers (methacrylate and epoxide) and demonstrate absorption maxima in the blue light wavelength range, which makes them potential candidates to work under the irradiation of a household blue LED bulb. Among all the investigated dihydroxyanthraquinone derivative-based photoinitiating systems, 18-DHAQ based systems exhibit the highest photoinitiating ability for both free radical and cationic photopolymerization while 12-DHAQ based systems are inefficient. It illustrates that the positions of hydroxyl substituents in the anthraquinone molecule play a significant role in the photoinitiating ability of dihydroxyanthraquinone derivatives. The photochemical mechanisms are investigated by fluorescence, laser flash photolysis, steady state photolysis, and electron spin resonance spin trapping techniques, and the results are in agreement with the relevant photopolymerization efficiency.

Length vs. stiffness: which plays a dominant role in the cellular uptake of fructose-based rod-like micelles by breast cancer cells in 2D and 3D cell culture models?

Polymeric nanoparticles with long circulation time hold great promise for anti-cancer drug delivery. An enhanced circulation effect of rod-like micelles has been reported, yet efficient intracellular delivery, especially their interactions with cells during endocytosis, still remains inconsistent. Internalization of rod-like nanoparticles is significantly affected by a number of factors including aspect ratio, stiffness and surface chemistry of nanoparticles. Our previous research has shown that the length of rods affected their cellular uptake by breast cancer cells. Here, the influence of rod stiffness in cellular uptake was investigated to provide a comprehensive understanding of the interaction between rods and cells during endocytosis. Well-defined fructose-coated rod-like micelles of different lengths and stiffness were prepared successfully. The AFM results indicate that rods based on poly(1-O-MAFru)31-b-PMMA166 are significantly stiffer than those prepared from poly(1-O-MAFru)31-b-PBA158. The cellular uptake of these different rod-like micelles by breast cancer cells was investigated. In vitro studies via 2D and 3D cell culture models reveal that stiffer rods exhibit a higher cellular uptake and a deeper penetration into cells than the soft rod-like micelles. These results indicate that the internalization of rod-like micelles is significantly affected by their stiffness, though the length of rods also plays an important role. Our results yield a fundamental understanding of the stiffness effect of rod-like micelles on cellular uptake.

Multihydroxy-Anthraquinone Derivatives as Free Radical and Cationic Photoinitiators of Various Photopolymerizations under Green LED

Multihydroxy-anthraquinone derivatives [i.e., 1,2,4-trihydroxyanthraquinone (124-THAQ), 1,2,7-trihydroxyanthraquinone (127-THAQ), and 1,2,5,8-tetrahydroxyanthraquinone (1258-THAQ)] can interact with various additives [e.g., iodonium salt, tertiary amine, N-vinylcarbazole, and 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-triazine] under household green LED irradiation to generate active species (cations and radicals). The relevant photochemical mechanism is investigated using quantum chemistry, fluorescence, cyclic voltammetry, laser flash photolysis, steady state photolysis, and electron spin resonance spin-trapping techniques. Furthermore, the multihydroxy-anthraquinone derivative-based photoinitiating systems are capable of initiating cationic photopolymerization of epoxides or divinyl ethers under green LED, and the relevant photoinitiation ability is consistent with the photochemical reactivity (i.e., 124-THAQ-based photoinitiating system exhibits highest reactivity and photoinitiation ability). More interestingly, multihydroxy-anthraquinone derivative-based photoinitiating systems can initiate free radical crosslinking or controlled (i.e., reversible addition-fragmentation chain transfer) photopolymerization of methacrylates under green LED. It reveals that multihydroxy-anthraquinone derivatives can be used as versatile photoinitiators for various types of photopolymerization reactions.