Design of Polymers for Intracellular Protein and Peptide Delivery

Cheng, Yiyun

doi:10.1002/cjoc.202000655

Cited by 49 publications

(44 citation statements)

References 59 publications

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“…While covalent coupling of cell membrane translocating moieties to proteins can be used, various non‐covalent methods using lipids, peptides, and polymers have gained much attention due to the facile complex formation, without the risk of altered native function [6–8] . The synergistic and balanced inter‐macromolecular ionic, hydrophobic, and hydrogen‐bond (HB) interactions are essential to achieve complex stability, interactions with the cell membranes, and protein release to the cytosol [9, 10] .…”

Section: Figurementioning

confidence: 99%

Carbamoylated Guanidine‐Containing Polymers for Non‐Covalent Functional Protein Delivery in Serum‐Containing Media

2022

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Despite the high potential of controlling cellular processes and treating various diseases by intracellularly delivered proteins, current delivery systems exhibit poor efficiency due to poor serum stability, cellular entry, and cytosolic availability of proteins. Here, we report a novel functional group, phenyl carbamoylated guanidine (Ph‐CG), that greatly enhances the delivery efficiency to various types of cells. Owing to the substantially lowered pKa, the hydrophobic Ph‐CG offers optimized inter‐macromolecular interactions via enhanced hydrogen‐bonding and hydrophobic interactions. The coplanarity of Ph‐CG also leads to the better intracellular entry of protein complexes. Intracellularly delivered apoptosis‐inducing enzymes and antibodies significantly induce cell viability inhibitions in a serum‐containing medium. The newly developed Ph‐CG can be introduced to various existing carriers, leading to the realization of future therapeutic protein delivery.

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Section: Figurementioning

confidence: 99%

Carbamoylated Guanidine‐Containing Polymers for Non‐Covalent Functional Protein Delivery in Serum‐Containing Media

2022

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“…Chitosan (CS) is a biodegradable natural cationic polymer with antibiotic activity and mucoadhesive property 20 . Inspired by the outstanding transmucosal e ciency of uorocarbon modi ed CS (FCS) as reported in our previous study for intravesical-instillation-based bladder cancer treatment 21 , we speculated that FCS may also be employed for transdermal delivery of biomacromolecules (Fig. 1a).…”

Section: Introductionmentioning

confidence: 98%

Non-invasive transdermal delivery of biomacromolecules with fluorocarbon-modified chitosan for melanoma immunotherapy and transdermal vaccines

Zhu¹,

Wei²,

Jin³

et al. 2022

Preprint

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Transdermal drug delivery has been regarded as an alternative to oral delivery and subcutaneous injection for its non-invasiveness, improved patient compliance and avoidance of the first-pass effect. However, needleless transdermal delivery of biomacromolecules remains a challenge. Herein, a transdermal delivery platform is developed to achieve highly efficient non-invasive transdermal delivery of biomacromolecules. In this system, fluorocarbon modified chitosan (FCS) is optimized as an effective yet biocompatible transdermal carrier to assemble with different proteins including immune checkpoint blockade (ICB) antibodies, and antigens such as the spike (S) protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The formed FCS-containing nanocomplexes exhibited rather effective transdermal penetration ability via both intercellular and transappendageal routes. Interestingly, non-invasive transdermal delivery of ICB antibodies by FCS induced stronger immune responses to treat mouse melanoma compared to intravenous injection of free antibodies, while presenting reduced systemic toxicity. Moreover, transdermal delivery of SARS-CoV-2 vaccine using FCS-containing nanocomplexes resulted in comparable humoral immunity as well as improved cell immunity and immune memory compared to that achieved with subcutaneous vaccine injection. Thus, FCS-based transdermal delivery systems may provide a compelling opportunity to overcome the skin barrier for efficient transdermal delivery of biomacromolecules, widening the range of therapeutics that can be topically administered.

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“…Protein drugs have high potency and specificity compared to conventional small-molecule chemotherapeutics [ 10 ]. However, proteins are easily degraded by proteases and hard to penetrate through cell membranes to act on intracellular targets.…”

Section: Introductionmentioning

confidence: 99%

Targeted and intracellular delivery of protein therapeutics by a boronated polymer for the treatment of bone tumors

Yang

Zhou

Sun

et al. 2022

Bioactive Materials

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The treatment of malignant bone tumors by chemotherapeutics often receives poor therapeutic response due to the specific physiological bone environment, and thus calls for the development of new therapeutic options. Here, we reported a bone-targeted protein nanomedicine for this purpose. Saporin, a toxin protein, was co-assembled with a boronated polymer for intracellular protein delivery, and the formed nanoparticles were further coated with an anionic polymer poly (aspartic acid) to shield the positive charges on nanoparticles and provide the bone targeting function. The prepared ternary complex nanoparticles showed high bone accumulation both in vitro and in vivo , and could reverse the surface charge property from negative to positive after locating at tumor site triggered by tumor extracellular acidity. The boronated polymer in the de-shielded nanoparticles further promote intracellular delivery of saporin into tumor cells, exerting the anticancer activity of saporin by inactivation of ribosomes. As a result, the bone-targeted and saporin-loaded nanomedicine could kill cancer cells at a low saporin dose, and efficiently prevented the progression of osteosarcoma xenograft tumors and bone metastatic breast cancer in vivo . This study provides a facile and promising strategy to develop protein-based nanomedicines for the treatment of malignant bone tumors.

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Design of Polymers for Intracellular Protein and Peptide Delivery

Cited by 49 publications

References 59 publications

Carbamoylated Guanidine‐Containing Polymers for Non‐Covalent Functional Protein Delivery in Serum‐Containing Media

Carbamoylated Guanidine‐Containing Polymers for Non‐Covalent Functional Protein Delivery in Serum‐Containing Media

Non-invasive transdermal delivery of biomacromolecules with fluorocarbon-modified chitosan for melanoma immunotherapy and transdermal vaccines

Targeted and intracellular delivery of protein therapeutics by a boronated polymer for the treatment of bone tumors

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