A tumor extracellular pH-sensitive PD-L1 binding peptide nanoparticle for chemo-immunotherapy of cancer

Zhu, Wangwei; Bai, Yun; Zhang, Nan; Yan, Jianqing; He, Ziyun; Sun, Qiqi; Pu, Yuji; He, Bin; Ye, Xueting

doi:10.1039/d1tb00537e

Cited by 30 publications

(21 citation statements)

References 47 publications

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“…6a2), and stronger red fluorescence of DOX could be seen mainly in the nuclei. Compared with the quick nuclei cumulation of free DOX within 1 h of co-incubation, 21 the slower nuclei cumulation here demonstrated the sustained drug release behavior of the proposed copolyprodrug nanoparticles due to the slow drug release from the copolyprodrug nanoparticles occurring as an interfacial process, as discussed in the HPLC analysis and the in vitro drug release profiles.…”

Section: Resultsmentioning

confidence: 58%

Synthesis and self-assembly of an acid/reduction co-triggered degradable amphiphilic copolyprodrug as a tumor-selective drug self-delivery system

Liu

2022

J. Mater. Chem. B

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Section: Resultsmentioning

confidence: 58%

Synthesis and self-assembly of an acid/reduction co-triggered degradable amphiphilic copolyprodrug as a tumor-selective drug self-delivery system

Liu

2022

J. Mater. Chem. B

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“…Due to the lack of in vivo selectivity 25 , a targeting D-type anti-PD-L1 peptide (NYSKPTDRQYHF, aPD-L1) was incorporated into the MP9 conjugate (Figure 3 A). This aPD-L1 peptide improves protease resistance and facilitates PD-L1 binding 26 . A K d value of 4 μM was observed between the aPD-L1 peptide and PD-L1 protein in MST experiment (Figure 3 B), which is consistent with previous report 27 .…”

Section: Resultsmentioning

confidence: 99%

Polymer chimera of stapled oncolytic peptide coupled with anti-PD-L1 peptide boosts immunotherapy of colorectal cancer

Lu¹,

Zhang²,

Zhou³

et al. 2022

Theranostics

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Rationale: Scarce tumor mutation burden and neoantigens create tremendous obstacles for an effective immunotherapy of colorectal cancer (CRC). Oncolytic peptides rise as a promising therapeutic approach that boosts tumor-specific immune responses by inducing antigenic substances. However, the clinical application of oncolytic peptides has been hindered because of structural instability, proteolytic degradation, and undesired toxicity when administered systemically. Methods: Based on wasp venom peptide, an optimized stapled oncolytic peptide MP9 was developed with rigid α-helix, protease-resistance, and CRC cell cytotoxicity. By incorporating four functional motifs that include D-peptidomimetic inhibitor of PD-L1, matrix metalloproteinase-2 (MMP-2) cleavable spacer, and MP9 with 4-arm PEG, a novel peptide-polymer conjugate (PEG-MP9-aPDL1) was obtained and identified as the most promising systemic delivery vehicle with PD-L1 targeting specificity and favorable pharmacokinetic properties. Results: We demonstrated that PEG-MP9-aPDL1-driven oncolysis induces a panel of immunogenic cell death (ICD)-relevant damage-associated molecular patterns (DAMPs) both in vitro and in vivo , which are key elements for immunotherapy with PD-L1 inhibitor. Further, PEG-MP9-aPDL1 exhibited prominent immunotherapeutic efficacy in a CRC mouse model characterized by tumor infiltration of CD8+ T cells and induction of cytotoxic lymphocytes (CTLs) in the spleens. Conclusion: Our findings suggest that PEG-MP9-aPDL1 is an all-in-one platform for oncolytic immunotherapy and immune checkpoint blockade (ICB).

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“…Among the immune-related peptides, D-PPA [NYSKPTDRQYHF] is a PD-L1-binding peptide developed by Chang et al Their study demonstrated that the hydrophilic D-type polypeptide (D-PPA) itself did not have cytotoxicity; however, through blocking the PD-1/PD-L1 interaction, it could inhibit tumor growth and prolong animal survival in CT26 tumor-bearing mice [ 18 ]. In other studies, Zhu et al made a conjugate-based PD-L1-binding nanoparticle with doxorubicin [ 62 ]. A hydrophilic D-PPA polypeptide was linked with two hydrophobic stearyl chains via a pH-sensitive linker to form amphiphilic PD-L1-binding peptide conjugate (DCS)-based nanoparticles.…”

Section: Peptides For Anticancer Therapymentioning

confidence: 99%

Peptide-Based Bioconjugates and Therapeutics for Targeted Anticancer Therapy

et al. 2022

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With rapidly growing knowledge in bioinformatics related to peptides and proteins, amino acid-based drug-design strategies have recently gained importance in pharmaceutics. In the past, peptide-based biomedicines were not widely used due to the associated severe physiological problems, such as low selectivity and rapid degradation in biological systems. However, various interesting peptide-based therapeutics combined with drug-delivery systems have recently emerged. Many of these candidates have been developed for anticancer therapy that requires precisely targeted effects and low toxicity. These research trends have become more diverse and complex owing to nanomedicine and antibody–drug conjugates (ADC), showing excellent therapeutic efficacy. Various newly developed peptide–drug conjugates (PDC), peptide-based nanoparticles, and prodrugs could represent a promising therapeutic strategy for patients. In this review, we provide valuable insights into rational drug design and development for future pharmaceutics.

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A tumor extracellular pH-sensitive PD-L1 binding peptide nanoparticle for chemo-immunotherapy of cancer

Abstract: Chemo-immunotherapy is a promising model for combination treatment of cancer. Many solid tumors overexpress programmed cell death ligand (PD-L1) for immune suppression. In this study, a PD-L1 binding peptide conjugate...

Cited by 30 publications

References 47 publications

Synthesis and self-assembly of an acid/reduction co-triggered degradable amphiphilic copolyprodrug as a tumor-selective drug self-delivery system

Synthesis and self-assembly of an acid/reduction co-triggered degradable amphiphilic copolyprodrug as a tumor-selective drug self-delivery system

Polymer chimera of stapled oncolytic peptide coupled with anti-PD-L1 peptide boosts immunotherapy of colorectal cancer

Peptide-Based Bioconjugates and Therapeutics for Targeted Anticancer Therapy

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