Peptide-Drug Conjugate: A Novel Drug Design Approach

Ma, Liang; Wang, Chao; He, Zihao; Cheng, Biao; Zheng, Ling; Huang, Kun

doi:10.2174/0929867324666170404142840

Cited by 89 publications

(71 citation statements)

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“…One of the main drawbacks of PDCs is their short half‐life in blood, due to their relatively small size, and these conjugates are susceptible to clearance. However, their rapid tissue distribution compensates for this unfavorable characteristic . To date, multiple cell‐penetrating and tumor‐homing peptides have been developed, and some of them have already reached clinical trials .…”

Section: Peptide–drug Conjugatesmentioning

confidence: 99%

Protease‐activated prodrugs: strategies, challenges, and future directions

Poręba

2020

The FEBS Journal

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Proteases play critical roles in virtually all biological processes, including proliferation, cell death and survival, protein turnover, and migration. However, when dysregulated, these enzymes contribute to the progression of multiple diseases, with cancer, neurodegenerative disorders, inflammation, and blood disorders being the most prominent examples. For a long time, disease-associated proteases have been used for the activation of various prodrugs due to their well-characterized catalytic activity and ability to selectively cleave only those substrates that strictly correspond with their active site architecture. To date, versatile peptide sequences that are cleaved by proteases in a site-specific manner have been utilized as bioactive linkers for the targeted delivery of multiple types of cargo, including fluorescent dyes, photosensitizers, cytotoxic drugs, antibiotics, and pro-antibodies. This platform is highly adaptive, as multiple protease-labile conjugates have already been developed, some of which are currently in clinical use for cancer treatment. In this review, recent advancements in the development of novel protease-cleavable linkers for selective drug delivery are described. Moreover, the current limitations regarding the selectivity of linkers are Abbreviations AAC, antibody-antibiotic conjugate; Ab, antibody; ACC, 7-amino-4-carbamoylmethylcoumarin; ADAM, a disintegrin and metalloproteinase; ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; ADC, antibody-drug conjugate; aPSs, activatable photosensitizers; BHQ-3, black hole quencher 3; Boc, tert-butyloxycarbonyl group; BT20, a type of mammary gland carcinoma; Cas9, CRISPR-associated protein 9;

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Section: Peptide–drug Conjugatesmentioning

confidence: 99%

Protease‐activated prodrugs: strategies, challenges, and future directions

Poręba

2020

The FEBS Journal

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“…Peptide-drug conjugates (PDCs), which are usually composed of the peptide, the small molecule drug, and a cleavable or noncleavable linker, are an emerging technology that has resulted in many PDCs in the developmental phase of preclinical and clinical studies. 146 PDCs have yet to get marketing approval from regulatory agencies. 146 Zoptarelin doxorubicin, consisting of doxorubicin linked to a small peptide agonist to the luteinizing hormonereleasing hormone (LHRH) receptor, has been evaluated in phase 3 clinical trials in a number of human cancers.…”

Section: Lectinsmentioning

confidence: 99%

“…146 PDCs have yet to get marketing approval from regulatory agencies. 146 Zoptarelin doxorubicin, consisting of doxorubicin linked to a small peptide agonist to the luteinizing hormonereleasing hormone (LHRH) receptor, has been evaluated in phase 3 clinical trials in a number of human cancers. 147. GRN1005 is a PDC composed of paclitaxel covalently linked to a peptide, angiopep-2, that targets the low-density lipoprotein receptor-related protein 1.…”

Section: Lectinsmentioning

confidence: 99%

<p>Smart Targeting To Improve Cancer Therapeutics</p>

Morales‐Cruz¹,

Delgado²,

Castillo³

et al. 2019

DDDT

109

101

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Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loaded particles) that utilize passive targeting, active targeting, and/or stimulus responsiveness strategies. This review will summarize some main ideas about the effect of each strategy and how the combination of some or all of them has shown to be effective. After a brief introduction of current cancer therapies and their limitations, we describe the biological barriers that nanoparticles need to overcome, followed by presenting different types of drug delivery systems to improve drug accumulation in tumors. Then, we describe cancer cell membrane targets that increase cellular drug uptake through active targeting mechanisms. Stimulusresponsive targeting is also discussed by looking at the intra-and extracellular conditions for specific drug release. We include a significant amount of information summarized in tables and figures on nanoparticle-based therapeutics, PEGylated drugs, different ligands for the design of active-targeted systems, and targeting of different organs. We also discuss some still prevailing fundamental limitations of these approaches, eg, by occlusion of targeting ligands.

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“…The polypeptides and nucleic acid aptamers with Mutp53 reactivating properties show reduced side effects due to their high binding specificity to target (Chen et al, ; Tal et al, ), but the poor solubility or stability of these macromolecules makes efficient drug delivery another challenge. Polypeptides usually need to be decorated or fused with a cell‐penetrating peptide to modulate their amphiphilicity (Copolovici, Langel, Eriste, & Langel, ; Ma et al, ). RNA needs to be enclosed in nanoparticles (Fan et al, ).…”

Section: Gaps From Bench To Bedsidementioning

confidence: 99%

Salvation of the fallen angel: Reactivating mutant p53

Yang

Wang

Chen

et al. 2019

British J Pharmacology

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The transcription factor p53 is known as the guardian of the genome for its powerful anti-tumour capacity. However, mutations of p53 that undermine their protein structure, resulting in loss of tumour suppressor function and gain of oncogenic function, have been implicated in more than half of human cancers. The crucial role of mutant forms of p53 in cancer makes it an attractive therapeutic target. A large number of candidates, including low MW compounds, peptides, and nucleic acids, have been identified or designed to rescue p53 mutants and reactivate their anti-tumour capacity through a variety of mechanisms. In this review, we summarize the progress made in the reactivation of mutant forms of p53, focusing on the pharmacological mechanisms of the reactivators of p53 mutants.

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Peptide-Drug Conjugate: A Novel Drug Design Approach

Cited by 89 publications

References 0 publications

Protease‐activated prodrugs: strategies, challenges, and future directions

Protease‐activated prodrugs: strategies, challenges, and future directions

<p>Smart Targeting To Improve Cancer Therapeutics</p>

Salvation of the fallen angel: Reactivating mutant p53

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