Research Field 5

 Li, Z. et. al., ACS Macro Lett., 2023, 12, 10, 1384–1388, https://doi.org/10.1021/acsmacrolett.3c00493

Hydrogen-bonding (H-bonding) assembly incorporated with an aggregation-induced emission (AIE) capability can serve as a powerful tool for developing supramolecular nanomedicine with clear tumor imaging and smart therapeutic performance. We here report a H-bonded polymeric nanoformulation with an AIE characteristic toward smart antitumor therapy. To do so, we first design a structurally novel tetraphenylethylene (TPE)-based H-bonding theranostic prodrug, TPE-(FUA)₄, characterized by four chemotherapeutic fluorouracil-1-acetic acid (FUA) moieties arched to the TPE core. A six-arm star-shaped amphiphilic polymer vehicle, P(DAP-co-OEGEA)₆, is prepared, bearing hydrophilic and biocompatible POEGEA (poly(oligo (ethylene glycol) ethyl acrylate) segments, along with a hydrophobic and H-bonding PDAP (poly(diaminopyridine acrylamide)) segment. Thanks to the establishment of the DAP/FUA H-bonding association, incorporating the TPE-(FUA)₄ prodrug to the P(DAP-co-OEGEA)₆ vehicle can yield H-bond cross-linked nanoparticles with interpenetrating networks. For the first time, AIE luminogens are interwoven into a six-arm star-shaped polymer via an intrinsic H-bonding array of the chemotherapeutic agent FUA, thus imposing an effective restriction of TPE molecular rotations. Concomitantly, encapsulated photothermal agent (IR780) via a hydrophobic interaction facilitates the formation of nanoassemblies, TPE-(FUA)4/IR780@P(DAP-co-OEGEA)₆, featuring synergistic cancer chemo/photothermal therapy (CT/PTT). Copyright © 2023, American Chemical Society

Thümmler, J. F. et al., Chemical Communications, 2023, DOI https://doi.org/10.1039/D3CC03851C

NIR-fluorescent LCST-type single-chain nanoparticles (SCNPs) change their photophysical behaviour upon heating, caused by depletion of water from the swollen SCNP interiors. This thermoresponsive effect leads to a fluctuating photoacoustic (PA) signal which can be used as a contrast mechanism for PA imaging. Rublished with a permission of the Royal Society of Chemistry 2023.

Qiu, X. et al., Biomacromolecules, 2022, 4519–4531,

https://pubs.acs.org/doi/10.1021/acs.biomac.2c00656

Chemodynamic therapy (CDT) reflects an innovative cancer treatment modality. To enhance its relatively low therapeutic efficiency, rational combination with extra therapeutic modes is highly appreciated. Here, core-coordinated amphiphilic, elliptic polymer nanoparticles (Cu/CBL–POEGEA NPs) are constructed via the self-assembly of a glutathione (GSH)-responsive polymer–drug conjugate. Side-chain acylthiourea (ATU) motifs are affixed, which behave as ligands capable of coordinating Cu(II). Benefitting from the GSH-induced reduction reaction, Cu(II) is converted into Cu(I) and subsequently react with endogenous H₂O₂ to create ^•OH, realizing GSH-depletion-promoted CDT. Additionally, the disulfide bond endows GSH-responsive CBL release and provokes further GSH decline, finally realizing combined CDT/CT toward enhancing antitumor outcomes, and in vitro as well as in vivo studies indeed reveal remarkable efficacy. Copyright © 2022, American Chemical Society.

Thümmler, J.F. et al., Chemical Communications, 2023, DOI https://doi.org/10.1039/D3CC03851C

NIR-fluorescent LCST-type single-chain nanoparticles (SCNPs) change their photophysical behaviour upon heating, caused by depletion of water from the swollen SCNP interiors. This thermoresponsive effect leads to a fluctuating photoacoustic (PA) signal which can be used as a contrast mechanism for PA imaging. Published with a permission of the Royal Society of Chemistry 2023.

Qiu, X. et al., Biomacromolecules, 2022, 4519–4531,

https://pubs.acs.org/doi/10.1021/acs.biomac.2c00656

Chemodynamic therapy (CDT) reflects an innovative cancer treatment modality. To enhance its relatively low therapeutic efficiency, rational combination with extra therapeutic modes is highly appreciated. Here, core-coordinated amphiphilic, elliptic polymer nanoparticles (Cu/CBL–POEGEA NPs) are constructed via the self-assembly of a glutathione (GSH)-responsive polymer–drug conjugate. Side-chain acylthiourea (ATU) motifs are affixed, which behave as ligands capable of coordinating Cu(II). Benefitting from the GSH-induced reduction reaction, Cu(II) is converted into Cu(I) and subsequently react with endogenous H₂O₂ to create ^•OH, realizing GSH-depletion-promoted CDT. Additionally, the disulfide bond endows GSH-responsive CBL release and provokes further GSH decline, finally realizing combined CDT/CT toward enhancing antitumor outcomes, and in vitro as well as in vivo studies indeed reveal remarkable efficacy. Copyright © 2022, American Chemical Society

Lechner E. et al., International Journal of Pharmaceutics, 2023, 123268,

https://doi.org/10.1016/j.ijpharm.2023.123268

There is growing need for new drug delivery sytems for intracochlear application of drugs to effectively treat inner ear disorders. In this study, we describe the development and characterization of biodegradable, triamcinolone-loaded implants based on poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol–poly(lactic-co-glycolic acid) (PEG-PLGA) respectively, prepared by hot-melt extrusion. PEG 1500 was used as a plasticizer to improve flexibility and accelerate drug release. PEG-PLGA implants showed an initial slow release rate over several days regardless of the amount of PEG added. Mathematical simulations of the pharmacokinetics of the inner ear based on the in vitro release kinetics indicate a complete distribution of triamcinolone in the whole human scala tympani, which underlines the high potential of the developed formulation. © 2023 The Authors. Published by Elsevier B.V.

Du, F., et al. Int. J. Pharmaceutics, 2022, DOI:https://doi.org/10.1016/j.ijpharm.2022.122023   

The polymer/solvent system poly (l-lactic acid)/ethyl butylacetylaminopropionate (PLLA/IR3535) is regarded as an insect-repellent-delivery system, serving, e.g., for fighting mosquito-borne tropical diseases. In this work, samples of the polymer/repellent system PLLA/IR3535 were prepared by 3D-printing. The experiments showed that it is possible to print 3D-parts containing up to 25 m% repellent, with an only minor loss of repellent during the printing process. The study successfully proved the applicability of the technology of extrusion-based 3D-printing for the preparation of polymer parts with a specific shape/design containing mosquito-repellent at a concentration which raises the expectation to be used as a repellent delivery-device.

Hilgeroth, P., et al. Polymers, 2022, DOI:https://doi.org/10.3390/polym14183742

Additive manufacturing has a wide range of applications and has opened up new methods of drug formulation, in turn achieving attention in medicine. We prepare and use styrene–isobutylene–styrene triblock copolymers (SIBS; Mn = 10 kDa–25 kDa, PDI 1,3–1,6) as a drug carrier for triamcinolone acetonide (TA), further processed by fused deposition modeling to create a solid drug release system displaying improved bioavailability and applicability. Continuous drug release and morphological investigations were conducted to probe the influence of the 3D printing process on the drug release, enabling 3D printing as a formulation method for a slow-release system of Triamcinolone.

Thümmler, J. F., et al. Macromol. Rapid. Commun., 2022, DOI:https://doi.org/10.1002/marc.202200618

Controlling the internal structures of single-chain nanoparticles (SCNPs) is an important factor for their targeted chemical design and synthesis, especially in view of nanosized compartments presenting different local environments as a main feature to control functionality. We here design SCNPs (sized 6 – 12 nm) bearing near-infrared fluorescent dyes embedded in hydrophobic compartments for use as contrast agents in pump–probe photoacoustic (PA) imaging. SCNPs with the dye molecules accumulate at the core and show a nonlinear PA response as a function of pulse energy—a property that can be exploited as a contrast mechanism in molecular PA tomography.

Wu, Y., et al. Polym. Chem., 2022, DOI:https://pubs.rsc.org/en/content/articlelanding/2022/py/d1py01634b

Integrating biomedical applications (e.g., drug delivery) into supramolecular chemistry is a promising strategy. This work targets the construction of hydrogen-bonded (H-bonded) supramolecular polymeric micelles loaded with chemotherapy drugs (carmofur) and photothermal agents (IR780) for combined chemo-photothermal therapies (CT/PTT).