Functionalised thermally induced phase separation (TIPS) microparticles enabled for “click” chemistry

Nogueira, João C. F.; Paliashvili, Ketevan; Bradford, Alexandra; Maggio, Francesco; Richards, Daniel A.; Day, Richard M.; Chudasama, Vijay

doi:10.1039/d0ob00106f

Cited by 7 publications

(6 citation statements)

References 25 publications

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“…The monobromo derivative was selective for cysteine residues (Z HER2:2395 –Cys) and the dibromo for disulfide bridges (Ontruzant, Ontruzant Fab). [ 54 ] See Figure S21 in the Supporting Information for chemical structures of both pyridazinedione linkers. Previous work by Bahou and Chudasama have shown that these linkers have negligible impact on stability and antigen binding.…”

Section: Resultsmentioning

confidence: 99%

Modular Synthesis of Semiconducting Graft Copolymers to Achieve “Clickable” Fluorescent Nanoparticles with Long Circulation and Specific Cancer Targeting

et al. 2023

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Semiconducting polymer nanoparticles (SPNs) are explored for applications in cancer theranostics because of their high absorption coefficients, photostability, and biocompatibility. However, SPNs are susceptible to aggregation and protein fouling in physiological conditions, which can be detrimental for in vivo applications. Here, a method for achieving colloidally stable and low‐fouling SPNs is described by grafting poly(ethylene glycol) (PEG) onto the backbone of the fluorescent semiconducting polymer, poly(9,9′‐dioctylfluorene‐5‐fluoro‐2,1,3‐benzothiadiazole), in a simple one‐step substitution reaction, postpolymerization. Further, by utilizing azide‐functionalized PEG, anti‐human epidermal growth factor receptor 2 (HER2) antibodies, antibody fragments, or affibodies are site‐specifically “clicked” onto the SPN surface, which allows the functionalized SPNs to specifically target HER2‐positive cancer cells. In vivo, the PEGylated SPNs are found to have excellent circulation efficiencies in zebrafish embryos for up to seven days postinjection. SPNs functionalized with affibodies are then shown to be able to target HER2 expressing cancer cells in a zebrafish xenograft model. The covalent PEGylated SPN system described herein shows great potential for cancer theranostics.

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Section: Resultsmentioning

confidence: 99%

Modular Synthesis of Semiconducting Graft Copolymers to Achieve “Clickable” Fluorescent Nanoparticles with Long Circulation and Specific Cancer Targeting

et al. 2023

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“… 19 , 33 Furthermore, TIPS PLGA microcarriers have been broadly characterized for various applications, which include myogenesis-related studies. 11 , 12 , 34–36 The work reported herein is the first to combine these areas of expertise to prepare a tissue-engineered combined product with the goal of treating fecal incontinence. This condition still misses a reliable treatment highly due to the inefficient cell delivery typically used in Regenerative Medicine approaches.…”

Section: Discussionmentioning

confidence: 99%

Developing a Cell-Microcarrier Tissue-Engineered Product for Muscle Repair Using a Bioreactor System

Cartaxo,

Fernandes-Platzgummer,

Rodrigues

et al. 2023

Tissue Engineering Part C: Methods

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Fecal incontinence, although not life-threatening, has a high impact on the economy and patient quality of life. So far, available treatments are based on both surgical and nonsurgical approaches. These can range from changes in diet, to bowel training, or sacral nerve stimulation, but none of which provides a long-term solution. New regenerative medicine-based therapies are emerging, which aim at regenerating the sphincter muscle and restoring continence. Usually, these consist of the administration of a suspension of expanded skeletal-derived muscle cells (SkMDCs) to the damaged site. However, this strategy often results in a reduced cell viability due to the need for cell harvesting from the expansion platform, as well as the non-native use of a cell suspension to deliver the anchorage-dependent cells. In this study, we propose the proof-of-concept for the bioprocessing of a new cell delivery method for the treatment of fecal incontinence, obtained by a scalable two-step process. First, patient-isolated SkMDCs were expanded using planar static culture systems. Second, by using a single-use PBS-MINI Vertical-Wheel ® bioreactor, the expanded SkMDCs were combined with biocompatible and biodegradable (i.e., directly implantable) poly(lactic- co -glycolic acid) microcarriers prepared by thermally induced phase separation. This process allowed for up to 80% efficiency of SkMDCs to attach to the microcarriers. Importantly, SkMDCs were viable during all the process and maintained their myogenic features (e.g., expression of the CD56 marker) after adhesion and culture on the microcarriers. When SkMDC-containing microcarriers were placed on a culture dish, cells were able to migrate from the microcarriers onto the culture surface and differentiate into multinucleated myotubes, which highlights their potential to regenerate the damaged sphincter muscle after administration into the patient. Overall, this study proposes an innovative method to attach SkMDCs to biodegradable microcarriers, which can provide a new treatment for fecal incontinence. Impact statement At present, no life-long treatment for fecal incontinence exists. New regenerative medicine-based therapies can be seen as a new avenue to solve this burdening health situation. Our approach relies on the administration of implantable biodegradable microcarriers that deliver cells capable of regenerating muscle to the damaged sphincter. In this study, we demonstrate the feasibility of using single-use, bioreactor technology for developing a cell-microcarrier combined product. Moreover, we show that the microcarrier-attached cells, due to their differentiation capacity and the presence of myogenic markers, display muscle regenerative potential, and are likely to be able to provide life-lasting repairs to the damaged muscle.

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“…Another key application that has benefited from employing PD-based bioconjugation strategies, is the formation of nanoparticle-antibody conjugates. 5,61,62 DiBrPDs in particular have been used extensively to site-selectively re-bridge antibody-fragments, which can then be attached to the surface of nanoparticles through efficient copper free "click" chemistries. Previous reports have shown that antibody-nanoparticle conjugates synthesised with antibody fragments (e.g.…”

Section: Orientated Nanoparticle-antibody Decorationmentioning

confidence: 99%

The use of bromopyridazinedione derivatives in chemical biology

Bahou¹,

Chudasama²

2022

Org. Biomol. Chem.

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Functionalised thermally induced phase separation (TIPS) microparticles enabled for “click” chemistry

Abstract: In this study we describe a novel platform for generating functionalised TIPS microparticles for “click” conjugation to various active compounds.

Cited by 7 publications

References 25 publications

Modular Synthesis of Semiconducting Graft Copolymers to Achieve “Clickable” Fluorescent Nanoparticles with Long Circulation and Specific Cancer Targeting

Modular Synthesis of Semiconducting Graft Copolymers to Achieve “Clickable” Fluorescent Nanoparticles with Long Circulation and Specific Cancer Targeting

Developing a Cell-Microcarrier Tissue-Engineered Product for Muscle Repair Using a Bioreactor System

The use of bromopyridazinedione derivatives in chemical biology

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