Targeted delivery by pH-responsive mPEG-S-PBLG micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity

Feng, Qiyi; Xu, Junhuai; Liu, Xinyi; Wang, Haibo; Xiong, Junjie; Xiao, Kai

doi:10.1080/10717544.2021.2008052

Cited by 8 publications

(5 citation statements)

References 51 publications

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“…Interestingly, the hydrolysis rate of β-thiopropionate can be adjusted by varying the number of methylene units, such as the length of a sulfide. 112 Recently, Feng et al 112 onate groups. This copolymer could self-assemble into micelles to encapsulate DOX and displayed acidity-sensitive stability.…”

Section: Response Mechanisms Of Tme Acidity-sensitive Polymersmentioning

confidence: 99%

“…Of the six different acidity-responsive covalent bonds, hemiaminal ether bonds , and acetal bonds − are most frequently used to construct polymerizable monomers for the fabrication of acidity responsive polymers. However, amide bonds, , imine bonds, − ester bonds, − and hydrazone bonds − are more commonly introduced through postmodification strategies. The degradation of these chemical bonds can usually be determined by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC).…”

Section: Response Mechanisms Of Tme Acidity-sensitive Polymersmentioning

confidence: 99%

“…The β-thiopropionate group is easily synthesized via a thiol–ene click reaction, which has been shown to be efficient, green, and easy. , Compared to acetal, amide, and imine groups, β-thiopropionate is relatively stable at neutral pH but slowly hydrolyzes under weakly acidic conditions due to the inductive effect of the sulfur atom, which leads to a partial positive charge on the ester carbonyl carbon. Interestingly, the hydrolysis rate of β-thiopropionate can be adjusted by varying the number of methylene units, such as the length of a sulfide . Recently, Feng et al designed an amphiphilic block copolymer composed of mPEG and poly( N -carbobenzoxy- l -glutamic acid) (PBLG) blocks containing β-thiopropionate groups.…”

Section: Response Mechanisms Of Tme Acidity-sensitive Polymersmentioning

confidence: 99%

“…Interestingly, the hydrolysis rate of β-thiopropionate can be adjusted by varying the number of methylene units, such as the length of a sulfide . Recently, Feng et al designed an amphiphilic block copolymer composed of mPEG and poly( N -carbobenzoxy- l -glutamic acid) (PBLG) blocks containing β-thiopropionate groups. This copolymer could self-assemble into micelles to encapsulate DOX and displayed acidity-sensitive stability.…”

Section: Response Mechanisms Of Tme Acidity-sensitive Polymersmentioning

confidence: 99%

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Targeted Delivery of Anticancer Therapeutics with Polymers by Harnessing Tumor Microenvironment Acidity

Shi,

Ma,

Zhang

et al. 2023

Chem. Mater.

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Cancer therapy is a global biomedical challenge, and a number of promising anticancer therapeutics, such as small-molecule drugs, proteins, nucleic acids, photothermal agents, etc., have been developed or are in development. However, the direct administration of anticancer therapeutics often fails to achieve the desired therapeutic efficacy due to their low bioavailability and poor tissue selectivity, leading to relapse or severe side effects such as immunosuppression, chronic inflammatory responses, mutagenesis, and long-term tissue dysfunction. Polymers offer multiple advantageous properties for the delivery of anticancer therapeutics but are generally poorly targeted to the tumor microenvironment (TME). The relatively lower acidity of the TME compared to normal tissue provides an intrinsic yet highly specific trigger for the development of polymers for the targeted delivery of anticancer therapeutics. Here, we summarize the exquisite strategies for the synthesis of TME acidity-sensitive polymers, elucidate the mechanisms of the polymers’ response to TME acidity, and highlight the applications of the polymers for the delivery of various anticancer therapeutics. Moreover, the potential challenges in translating the polymers into clinical practice are discussed.

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Section: Response Mechanisms Of Tme Acidity-sensitive Polymersmentioning

confidence: 99%

Section: Response Mechanisms Of Tme Acidity-sensitive Polymersmentioning

confidence: 99%

Section: Response Mechanisms Of Tme Acidity-sensitive Polymersmentioning

confidence: 99%

Section: Response Mechanisms Of Tme Acidity-sensitive Polymersmentioning

confidence: 99%

See 2 more Smart Citations

Targeted Delivery of Anticancer Therapeutics with Polymers by Harnessing Tumor Microenvironment Acidity

Shi,

Ma,

Zhang

et al. 2023

Chem. Mater.

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show abstract

“…Although the research on lignin-based pH-responsive polymers is still in its infancy, other types of pH-sensitive conjugates with different responsive mechanisms are rela-tively mature. For instance, a polymer fabricated with acid-unstable bonds, such as ester bonds [1][2][3], hydrazones [4,5], imines [6][7][8], phosphoramidates [9], acetals [10,11], cyclic acetals [12], and β-thiopropionate bonds [13][14][15], can realize pH response dissociation via the breaking of the weakly covalent bonds. Obviously, the ester bonds can be easily constructed in lignin by a simple esterification reaction.…”

Section: Introductionmentioning

confidence: 99%

A pH-Sensitive Lignin-Based Material for Sustained Release of 8-Hydroxyquinoline

Zheng

Chai

et al. 2023

Polymers

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The fabrication of pH-sensitive lignin-based materials has received considerable attention in various fields, such as biomass refining, pharmaceuticals, and detecting techniques. However, the pH-sensitive mechanism of these materials is usually depending on the hydroxyl or carboxyl content in the lignin structure, which hinders the further development of these smart materials. Here, a pH-sensitive lignin-based polymer with a novel pH-sensitive mechanism was constructed by establishing ester bonds between lignin and the active molecular 8-hydroxyquinoline (8HQ). The structure of the produced pH-sensitive lignin-based polymer was comprehensively characterized. The substituted degree of 8HQ was tested up to 46.6% sensitivity, and the sustained release performance of 8HQ was confirmed by the dialysis method, the sensitivity of which was found to be 60 times slower compared with the physical mixed sample. Moreover, the obtained pH-sensitive lignin-based polymer showed an excellent pH sensitivity, and the released amount of 8HQ under an alkaline condition (pH = 8) was obviously higher than that under an acidic condition (pH = 3 and 5). This work provides a new paradigm for the high-value utilization of lignin and a theory guidance for the fabrication of novel pH-sensitive lignin-based polymers.

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Research progress of therapeutic drugs for doxorubicin-induced cardiomyopathy

Chen¹,

Shi²,

Dai³

2022

Biomedicine & Pharmacotherapy

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Targeted delivery by pH-responsive mPEG-S-PBLG micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity

Cited by 8 publications

References 51 publications

Targeted Delivery of Anticancer Therapeutics with Polymers by Harnessing Tumor Microenvironment Acidity

Targeted Delivery of Anticancer Therapeutics with Polymers by Harnessing Tumor Microenvironment Acidity

A pH-Sensitive Lignin-Based Material for Sustained Release of 8-Hydroxyquinoline

Research progress of therapeutic drugs for doxorubicin-induced cardiomyopathy

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