Poly(2-ethyl-2-oxazoline) conjugates with doxorubicin for cancer therapy: In vitro and in vivo evaluation and direct comparison to poly[N-(2-hydroxypropyl)methacrylamide] analogues

Sedláček, Ondřej; Monnery, Bryn D.; Mattová, Jana; Kučka, Jan; Pánek, Jiří; Janoušková, Olga; Höcherl, Anita; Verbraeken, Bart; Vergaelen, Maarten; Zadinová, M; Hoogenboom, Richard; Hrubý, Martin

doi:10.1016/j.biomaterials.2017.09.003

Cited by 91 publications

(75 citation statements)

References 52 publications

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“…The lyophilised polymers reacted with ninhydrin to slowly form Ruhemannsp urple,a nd were successfully modified with isothiocyanates in the presence of ab ase confirming the presence of the primary amino end group,which is consistent with previous reports. [12,[26][27][28] When the polymerisations were performed at 40 8 8Ci t yielded PEtOx polymers with extremely narrow dispersity and minimal shoulders in the size exclusion chromatograms with a < 1.06 up to ac hain length of 58 kDa at high monomer conversion of > 90 %(SEC;F igure 1, top;T able 1; see Table S1). Defined polymers with < 1.2 were also obtained when targeting higher molar masses at ca.…”

Section: Angewandte Chemiementioning

confidence: 99%

Defined High Molar Mass Poly(2‐Oxazoline)s

et al. 2018

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Poly(2-alkyl-2-oxazoline)s (PAOx) are regaining interest for biomedical applications.H owever,t heir full potential is hampered by the inability to synthesise uniform high-molar mass PAOx. In this work, we proposed alternative intrinsic chain transfer mechanisms based on 2-oxazoline and oxazolinium chain-end tautomerisation and derived improved polymerization conditions to suppress chain transfer,allowing the synthesis of highly defined poly(2-ethyl-2-oxazoline)s up to ca. 50 kDa (dispersity () < 1.05) and defined polymers up to at least 300 kDa ( < 1.2). The determination of the chain transfer constants for the polymerisations hinted towards the tautomerisation of the oxazolinium chain end as most plausible cause for chain transfer.Finally,the method was applied for the preparation of up to 60 kDa molar mass copolymers of 2-ethyl-2-oxazoline and 2-methoxycarbonylethyl-2-oxazoline.

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Section: Angewandte Chemiementioning

confidence: 99%

Defined High Molar Mass Poly(2‐Oxazoline)s

et al. 2018

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“…For further precisely analyzing the retention effect in vivo, CPT‐LFPR, CPT‐LGPR, or free CPT are IV injected into HeLa tumor‐bearing mice with the same protocol as above mentioned and the three groups of mice are sacrificed at day 2. The tumors are collected for determining the CPT concentration by homogenization and fluorescence measurement . As shown in Figure d, for free CPT, CPT‐ LGPR, and CPT‐ LFPR groups, the CPT accumulation in tumor is 1.32%, 2.21%, and 4.14% ID g −1 , respectively, where the highest CPT accumulation is detected in CPT‐LFPR treated tumor.…”

Section: Methodsmentioning

confidence: 99%

Site‐Specific Construction of Long‐Term Drug Depot for Suppression of Tumor Recurrence

Cheng

Zhang

Gao

et al. 2019

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Local tumor recurrence after surgical resection is a critical concern in cancer therapy, and the current treatments, such as postsurgical chemotherapy, still show undesired side effects. Here a nonimplant strategy (transformation induced localization, TIL) is presented to in situ construct long‐term retentive drug depots, wherein the sustained drug release from fibrous drug depots results in highly efficient suppression of postsurgical local tumor relapse. The peptide‐based prodrug nanoparticles show favorable tumor targeting and instantly reorganize into fibrous nanostructures under overexpressed enzyme, realizing the construction of long‐term drug depot in the tumor site. After the resection surgery, the remnant cancer cells are still inhibited by the sustained drug release from the fibrous prodrug depot, effectively preventing postsurgical local recurrences. This TIL strategy shows great potential in cancer recurrence therapy and offers a novel perspective for constructing functional biomaterials in vivo.

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“…On the other hand with PHPMA and poly(2‐oxazolines) it is possible to create uniform statistical copolymers (with polydispersity index PDI < 1.2) in combination with a wide choice of functionalized methacrylamides and 2‐oxazolines, using either the reversible addition − fragmentation chain‐transfer (RAFT) polymerization (for PHPMA) or the living cationic polymerization (for poly(2‐oxazolines)). When evaluated on in vivo murine models the systems based on PHPMA and poly(2‐oxazolines) have comparable properties . The most studied systems in past decades were antitumor conjugates of copolymers based on PHPMA of which some reached the stage of clinical testing …”

Section: Other Considerations and Comparison Of The Polymersmentioning

confidence: 99%

Physico‐Chemical Properties as a Key Factor in Choosing Practically Applicable Biocompatible Polymers

Hrubý

Štěpánek

Pánek

2019

Macromolecular Symposia

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Main principles of applicability of polymers for biomedical purposes with the emphasis on their physico‐chemical properties and solution behavior are reviewed. The influence of molecular weight of the polymers and their degradability are also discussed. Thermosensitive polymers are pointed out including additional effects such as hydrogen bonds and vitrification. Several examples of polymers currently used or under development are presented and their advantages and drawbacks are analyzed.

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Poly(2-ethyl-2-oxazoline) conjugates with doxorubicin for cancer therapy: In vitro and in vivo evaluation and direct comparison to poly[N-(2-hydroxypropyl)methacrylamide] analogues

Cited by 91 publications

References 52 publications

Defined High Molar Mass Poly(2‐Oxazoline)s

Defined High Molar Mass Poly(2‐Oxazoline)s

Site‐Specific Construction of Long‐Term Drug Depot for Suppression of Tumor Recurrence

Physico‐Chemical Properties as a Key Factor in Choosing Practically Applicable Biocompatible Polymers

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