Photocleavable core cross-linked polymeric micelles of polypept(o)ides and ruthenium(<scp>ii</scp>) complexes

Bauer, Tobias; Eckrich, Jonas; Wiesmann, Nadine; Kuczelinis, Felix; Sun, Wen; Zeng, Xiaolong; Weber, Benjamín; Wu, Si; Bings, Nicolas H.; Strieth, Sebastian; Barz, Matthias

doi:10.1039/d1tb01336j

Cited by 15 publications

(10 citation statements)

References 77 publications

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“…In a similar direction, recently, Barz et al prepared photocleavable core cross-linked polymeric micelles containing polypyridyl–ruthenium(II) complexes combined with polypept(o)ides ( Ru35 and Ru36 ) [ 116 ]. Block copolymers of polysarcosine- b -poly(glutamic acid) were synthesized and modified with aromatic nitrile groups on the glutamic acid side chain.…”

Section: Non-platinum-containing Metal Therapeutic Agents Loaded Into...mentioning

confidence: 99%

“…The ruthenium cross-linked micelles displayed colloidal stability in human blood plasma. Analysis in HuH-7 tumor cells revealed increased cytotoxicity via micellar delivery of [Ru(bpy) 2 (H 2 O) 2 ] 2+ (bpy = 2,2′-bipyridine) but mostly irradiation damage for [Ru(biq) 2 (H 2 O) 2 ] 2+ (biq = 2,2′-biquinoline) that could not be completely released by light-induced cleavage [ 116 ].…”

Section: Non-platinum-containing Metal Therapeutic Agents Loaded Into...mentioning

confidence: 99%

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Polymeric Nanosystems Applied for Metal-Based Drugs and Photosensitizers Delivery: The State of the Art and Recent Advancements

2022

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Nanotechnology-based approaches for targeting the delivery and controlled release of metal-based therapeutic agents have revealed significant potential as tools for enhancing the therapeutic effect of metal-based agents and minimizing their systemic toxicities. In this context, a series of polymer-based nanosized systems designed to physically load or covalently conjugate metal-based therapeutic agents have been remarkably improving their bioavailability and anticancer efficacy. Initially, the polymeric nanocarriers were applied for platinum-based chemotherapeutic agents resulting in some nanoformulations currently in clinical tests and even in medical applications. At present, these nanoassemblies have been slowly expanding for nonplatinum-containing metal-based chemotherapeutic agents. Interestingly, for metal-based photosensitizers (PS) applied in photodynamic therapy (PDT), especially for cancer treatment, strategies employing polymeric nanocarriers have been investigated for almost 30 years. In this review, we address the polymeric nanocarrier-assisted metal-based therapeutics agent delivery systems with a specific focus on non-platinum systems; we explore some biological and physicochemical aspects of the polymer–metallodrug assembly. Finally, we summarize some recent advances in polymeric nanosystems coupled with metal-based compounds that present potential for successful clinical applications as chemotherapeutic or photosensitizing agents. We hope this review can provide a fertile ground for the innovative design of polymeric nanosystems for targeting the delivery and controlled release of metal-containing therapeutic agents.

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Section: Non-platinum-containing Metal Therapeutic Agents Loaded Into...mentioning

confidence: 99%

Section: Non-platinum-containing Metal Therapeutic Agents Loaded Into...mentioning

confidence: 99%

Polymeric Nanosystems Applied for Metal-Based Drugs and Photosensitizers Delivery: The State of the Art and Recent Advancements

2022

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“…Afterwards the Salkylsulfonyl protective group can be reacted with thiols yielding unsymmetric disulfides for chemoselective bioconjugation or bioreversible cross-linking chemistry. [79][80][81][82] Based on this chemical tool box Matthias Barz synthesized core-crosslinked polymeric micelles, [79,[83][84][85] polymersomes, [86] nanohydrogels and polyplexes, [87] lipid nanoparticles, [88] molecular polymer brushes [89][90][91] and organic-inorganic hybrid systems. [89][90][91] In line with Rudolf Zentel's vision that every system shall be designed to fulfil a rational need, Matthias Barz's systems enable therapeutic interventions, e.g., in cancer diagnosis [89] and therapy, [92] (immune) therapy [91,93,94] and bacterial infections.…”

Section: How Did This Inspire Rudolf Zentel and Next Generations?mentioning

confidence: 99%

From Self‐Organization to Tumor‐Immune Therapy: How Things Started and How They Evolved

Barz

Nuhn

Hörpel³

et al. 2022

Macromol. Rapid Commun.

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BackgroundOn a sunny afternoon in summer 2021, Rudolf Zentel and Lutz Nuhn visited Helmut Ringsdorf in Mainz-Gonsenheim, Germany. It was the first time they were able to meet each other again in person after the long-lasting restrictions of the COVID-19 pandemic. While having a cup of coffee and a slice of cake on the garden terrace, Zentel and Ringsdorf looked back on the early days and "how things started and how they evolved". In a lively discussion the participants shared their thoughts on naïve ideas from the old days, how they continued, evolved and extended in the Zentel lab (Figure 1). These ideas were afterwards discussed and co-reflected by former students of the Ringsdorf lab (G. Hörpel, R. Zentel) and the Zentel lab (M. Barz, L.Nuhn). As a result, this perspective article was written, which brings together the individual opinions of the authors as -hopefully -a valuable contribution to Macromolecular Rapid Communication's special issue in honor of Rudolf Zentel upon his retirement. Starting PointThe starting point of the work in the Ringsdorf lab was polymer science in the 60s and 70s of the last century (or even better: "the last millennium", quotation by Ringsdorf). At that time, the beginning of the "plastic era" had just started a few decades previously, everything related to polymers was extremely modern, and research on this topic was well supported by chemical industries. Polymers and plastics entered everyday life as commodity

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“…[16] Moreover, (bio-) reversible drug conjugation strategies allow for external or disease-related controlled drug release from CCPMs. [17][18][19][20] As the most promising example, CCPMs containing pH-cleavable docetaxel (CPC634) are currently under clinical evaluation for the treatment of platinum-resistant ovarian cancer in phase II (NCT03742713). [11,21,22] The production of CCPMs typically involves the self-assembly of reactive block copolymers, cross-linking, (pro-) drug incorporation and purification, processes which require facile, robust, and scalable manufacturing.…”

Section: Introductionmentioning

confidence: 99%

“…[ 16 ] Moreover, (bio‐) reversible drug conjugation strategies allow for external or disease‐related controlled drug release from CCPMs. [ 17–20 ] As the most promising example, CCPMs containing pH‐cleavable docetaxel (CPC634) are currently under clinical evaluation for the treatment of platinum‐resistant ovarian cancer in phase II (NCT03742713). [ 11,21,22 ]…”

Section: Introductionmentioning

confidence: 99%

Complex Structures Made Simple – Continuous Flow Production of Core Cross‐Linked Polymeric Micelles for Paclitaxel Pro‐Drug‐Delivery

et al. 2023

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Translating innovative nanomaterials to medical products requires efficient manufacturing techniques that enable large‐scale high‐throughput synthesis with high reproducibility. Drug carriers in medicine embrace a complex subset of tasks calling for multifunctionality. Here, the synthesisof pro‐drug‐loaded core cross‐linked polymeric micelles (CCPMs) in a continuous flow processis reported, which combines the commonly separated steps of micelle formation, core cross‐linking, functionalization, and purification into a single process. Redox‐responsive CCPMs are formed from thiol‐reactive polypept(o)ides of polysarcosine‐block‐poly(S‐ethylsulfonyl‐l‐cysteine) and functional cross‐linkers based on dihydrolipoic acid hydrazide for pH‐dependent release of paclitaxel. The precisely controlled microfluidic process allows the production of spherical micelles (Dh = 35 nm) with low polydispersity values (PDI < 0.1) while avoiding toxic organic solvents and additives with unfavorable safety profiles. Self‐assembly and cross‐linking via slit interdigital micromixers produces 350–700 mg of CCPMs/h per single system, while purification by online tangential flow filtration successfully removes impurities (unimer ≤ 0.5%). The formed paclitaxel‐loaded CCPMs possess the desired pH‐responsive release profile, display stable drug encapsulation, an improved toxicity profile compared to Abraxane (a trademark of Bristol‐Myers Squibb), and therapeutic efficiency in the B16F1‐xenotransplanted zebrafish model. The combination of reactive polymers, functional cross‐linkers, and microfluidics enables the continuous‐flow synthesis of therapeutically active CCPMs in a single process.

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Photocleavable core cross-linked polymeric micelles of polypept(o)ides and ruthenium(ii) complexes

Abstract: Core cross-linking of polymeric micelles has been demonstrated to contribute to enhanced stability that can improve therapeutic efficacy. Photochemistry has the potential to provide spatial resolution and on-demand drug release....

Cited by 15 publications

References 77 publications

Polymeric Nanosystems Applied for Metal-Based Drugs and Photosensitizers Delivery: The State of the Art and Recent Advancements

Polymeric Nanosystems Applied for Metal-Based Drugs and Photosensitizers Delivery: The State of the Art and Recent Advancements

From Self‐Organization to Tumor‐Immune Therapy: How Things Started and How They Evolved

Complex Structures Made Simple – Continuous Flow Production of Core Cross‐Linked Polymeric Micelles for Paclitaxel Pro‐Drug‐Delivery

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