An orally available PD-1/PD-L1 blocking peptide OPBP-1-loaded trimethyl chitosan hydrogel for cancer immunotherapy

Li, Wanqiong; Zhu, Xueqiong; Zhou, Xiaoxi; Wang, Xiaoxi; Zhai, Wenjie; Li, Bingyu; Du, Jiangfeng; Li, Guodong; Sui, Xinghua; Wu, Yahong; Zhai, Mingxia; Qi, Yuanming; Chen, Guan-Yu; Gao, Yanfeng

doi:10.1016/j.jconrel.2021.04.036

Cited by 55 publications

(28 citation statements)

References 64 publications

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“…In addition, the PPD loaded hydrogel is able to prolong retention time within specific gut regions thus elevate the drug absorption. However, hydrogels for oral delivery of PPDs have not made significant progress towards the clinical trials 68 , 70 .…”

Section: Strategies To Enhance Oral Bioavailability Of Ppdsmentioning

confidence: 99%

“…Further, the stability of peptides can be improved by simple modification, such as terminal blocking and insertion of D-amino acids 137 . We have previously identified a PD-1/PD-L1 blocking D-peptide by using a liquid-phase phage display screening method, and it showed proteolysis-resistance and great stability in vivo , which is remarkably beneficial for its oral delivery 70 . Arginine-glycine-aspartic acid (RGD) is widely used ligands to target integrin αvβ3 receptors, which are transmembrane glycoproteins overexpressed in intestinal Caco-2 cell line 138 .…”

Section: Targeting Intestinal Cell For Oral Ppds Deliverymentioning

confidence: 99%

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Oral delivery of protein and peptide drugs: from non-specific formulation approaches to intestinal cell targeting strategies

Chen¹,

Kang²,

Li³

et al. 2022

Theranostics

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The past few years has witnessed a booming market of protein and peptide drugs, owing to their superior efficiency and biocompatibility. Parenteral route is the most commonly employed method for protein and peptide drugs administration. However, short plasma half-life protein and peptide drugs requires repetitive injections and results in poor patient compliance. Oral delivery is a promising alternative but hindered by harsh gastrointestinal environment and defensive intestinal epithelial barriers. Therefore, designing suitable oral delivery systems for peptide and protein drugs has been a persistent challenge. This review summarizes the main challenges for oral protein and peptide drugs delivery and highlights the advanced formulation strategies to improve their oral bioavailability. More importantly, major intestinal cell types and available targeting receptors are introduced along with the potential strategies to target these cell types. We also described the multifunctional biomaterials which can be used to prepare oral carrier systems as well as to modulate the mucosal immune response. Understanding the emerging delivery strategies and challenges for protein and peptide drugs will surely inspire the production of promising oral delivery systems that serves therapeutic needs in clinical settings.

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Section: Strategies To Enhance Oral Bioavailability Of Ppdsmentioning

confidence: 99%

Section: Targeting Intestinal Cell For Oral Ppds Deliverymentioning

confidence: 99%

Oral delivery of protein and peptide drugs: from non-specific formulation approaches to intestinal cell targeting strategies

Chen¹,

Kang²,

Li³

et al. 2022

Theranostics

Self Cite

View full text Add to dashboard Cite

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“…Gao et al. ( 138 ) screened the parent peptide H12 by phage display technology and subsequently optimized it. They obtained D-peptide A10Y (OPBP-1) with high PD-1/PD-L1 blocking activity and resistance to enzymatic degradation in the gastrointestinal environment.…”

Section: Hydrogel Materials For Combinatorial Immunotherapymentioning

confidence: 99%

Nanomaterials: A powerful tool for tumor immunotherapy

et al. 2022

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Cancer represents the leading global driver of death and is recognized as a critical obstacle to increasing life expectancy. In recent years, with the development of precision medicine, significant progress has been made in cancer treatment. Among them, various therapies developed with the help of the immune system have succeeded in clinical treatment, recognizing and killing cancer cells by stimulating or enhancing the body’s intrinsic immune system. However, low response rates and serious adverse effects, among others, have limited the use of immunotherapy. It also poses problems such as drug resistance and hyper-progression. Fortunately, thanks to the rapid development of nanotechnology, engineered multifunctional nanomaterials and biomaterials have brought breakthroughs in cancer immunotherapy. Unlike conventional cancer immunotherapy, nanomaterials can be rationally designed to trigger specific tumor-killing effects. Simultaneously, improved infiltration of immune cells into metastatic lesions enhances the efficiency of antigen submission and induces a sustained immune reaction. Such a strategy directly reverses the immunological condition of the primary tumor, arrests metastasis and inhibits tumor recurrence through postoperative immunotherapy. This paper discusses several types of nanoscale biomaterials for cancer immunotherapy, and they activate the immune system through material-specific advantages to provide novel therapeutic strategies. In summary, this article will review the latest advances in tumor immunotherapy based on self-assembled, mesoporous, cell membrane modified, metallic, and hydrogel nanomaterials to explore diverse tumor therapies.

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“…The PD-1/PD-L1 blocking peptide was co-administered with N , N , N -trimethyl chitosan, a hydrogel increasing the bioavailability of the peptide by 53% in mouse models. This made it possible to achieve not only inhibition of tumor growth but also an increase in tumor infiltration by CD8+ T cells and secretion of IFN-γ [ 99 ].…”

Section: Targeting Clinically Significant Ppis With Interfacial Peptidesmentioning

confidence: 99%

Interfacial Peptides as Affinity Modulating Agents of Protein-Protein Interactions

2022

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The identification of disease-related protein-protein interactions (PPIs) creates objective conditions for their pharmacological modulation. The contact area (interfaces) of the vast majority of PPIs has some features, such as geometrical and biochemical complementarities, “hot spots”, as well as an extremely low mutation rate that give us key knowledge to influence these PPIs. Exogenous regulation of PPIs is aimed at both inhibiting the assembly and/or destabilization of protein complexes. Often, the design of such modulators is associated with some specific problems in targeted delivery, cell penetration and proteolytic stability, as well as selective binding to cellular targets. Recent progress in interfacial peptide design has been achieved in solving all these difficulties and has provided a good efficiency in preclinical models (in vitro and in vivo). The most promising peptide-containing therapeutic formulations are under investigation in clinical trials. In this review, we update the current state-of-the-art in the field of interfacial peptides as potent modulators of a number of disease-related PPIs. Over the past years, the scientific interest has been focused on following clinically significant heterodimeric PPIs MDM2/p53, PD-1/PD-L1, HIF/HIF, NRF2/KEAP1, RbAp48/MTA1, HSP90/CDC37, BIRC5/CRM1, BIRC5/XIAP, YAP/TAZ–TEAD, TWEAK/FN14, Bcl-2/Bax, YY1/AKT, CD40/CD40L and MINT2/APP.

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An orally available PD-1/PD-L1 blocking peptide OPBP-1-loaded trimethyl chitosan hydrogel for cancer immunotherapy

Cited by 55 publications

References 64 publications

Oral delivery of protein and peptide drugs: from non-specific formulation approaches to intestinal cell targeting strategies

Oral delivery of protein and peptide drugs: from non-specific formulation approaches to intestinal cell targeting strategies

Nanomaterials: A powerful tool for tumor immunotherapy

Interfacial Peptides as Affinity Modulating Agents of Protein-Protein Interactions

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