In this article, we are investigating a series of organo-dyes, including methylene blue, fluorescein, rhodamine 6G, Nile red and eosin Y, to perform a visible light-mediated controlled/“living” radical polymerization of methacrylates. We demonstrate that eosin Y and fluorescein were efficient catalysts to activate a photoinduced electron transfer-reversible addition–fragmentation chain transfer (PET-RAFT) mechanism. The concentration of eosin Y was varied from 10 to 100 ppm with respect to monomers. This polymerization technique yielded well-defined (co)polymers with a good control of the molecular weights ranging from 10 000 to 100 000 g mol−1 and low polydispersities (PDI < 1.30). A variety of functional monomers, including N,N-dimethylaminoethyl methacrylate, hydroxyl ethyl methacrylate, pentafluorophenyl methacrylate, glycidyl methacrylate, oligoethylene glycol methyl ether methacrylate (OEGMA), and methacrylic acid, were successfully polymerized. Finally, the addition of a tertiary amine, such as triethylamine, afforded the polymerization in the presence of air via a reductive quenching cycle. Different diblock polymethacrylate copolymers, i.e. PMMA-b-POEGMA and PMMA-b-PMMA, were prepared to demonstrate the high end group fidelity.
In this paper, we describe the synthesis of asymmetric functional POEGMA-b-P(ST-co-VBA) copolymers in methanol, yielding in one-pot polymerization a range of nanoparticle morphologies, including spherical micelles, worm-like, rod-like micelles and vesicles. The presence of the aldehyde group was then exploited to form crosslinks or to conjugate chemotherapy compounds, such as doxorubicin, via pH-breakable bonds (Schiff base or imine) directly to the preformed nanoparticles. The influence of the nanoparticle morphologies on the MCF-7 breast cancer cell line uptake was investigated using flow cytometry and confocal microscopy. Finally, the IC50 of DOX, following nanoparticle delivery, was studied showing significant influence of the nanoparticle carrier morphology on therapeutic efficacy for breast cancer.
The rise of hospital-acquired infections, also known as nosocomial infections, is a growing concern in intensive healthcare, causing the death of hundreds of thousands of patients and costing billions of dollars worldwide every year. In addition, a decrease in the effectiveness of antibiotics caused by the emergence of drug resistance in pathogens living in biofilm communities poses a significant threat to our health system. The development of new therapeutic agents is urgently needed to overcome this challenge. We have developed new dual action polymeric nanoparticles capable of storing nitric oxide, which can provoke dispersal of biofilms into an antibiotic susceptible planktonic form, together with the aminoglycoside gentamicin, capable of killing the bacteria. The novelty of this work lies in the attachment of NO-releasing moiety to an existing clinically used drug, gentamicin. The nanoparticles were found to release both agents simultaneously and demonstrated synergistic effects, reducing the viability of Pseudomonas aeruginosa biofilm and planktonic cultures by more than 90% and 95%, respectively, while treatments with antibiotic or nitric oxide alone resulted in less than 20% decrease in biofilm viability.