Prodrugs for targeted cancer therapy

Souza, Carla; Pellosi, Diogo Silva; Tedesco, Antônio Cláudio

doi:10.1080/14737140.2019.1615890

Cited by 53 publications

(40 citation statements)

References 156 publications

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“…Prodrug technology has been applied to enhance its solubility, its tumor target and efficacy. 12 Several researchers have taken advantage of poly(ethylene glycol) PEG-based prodrug to synthesize cabazitaxel-PEG prodrugs that are capable of accumulating in prostate tumor tissues through passive targeting, the enhanced permeability and retention (EPR) effect. 13 , 14 Compared with passive targeting, prodrug-based active targeting (cancer cell-specific targeting) has attracted wide attention in cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Combination Therapy of Metastatic Castration-Recurrent Prostate Cancer: Hyaluronic Acid Decorated, Cabazitaxel-Prodrug and Orlistat Co-Loaded Nano-System

Ren

Shen

et al. 2021

DDDT

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Section: Introductionmentioning

confidence: 99%

Combination Therapy of Metastatic Castration-Recurrent Prostate Cancer: Hyaluronic Acid Decorated, Cabazitaxel-Prodrug and Orlistat Co-Loaded Nano-System

Ren

Shen

et al. 2021

DDDT

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“…Combinations of prodrugs with nanotechnology is a new strategy approach for the treatment that can overcome a lot of these drawbacks or limitations. (Souza et al, 2019). Catharanthus roseus (CR) AuNP nanocomplexes are used as drug delivery systems and are of immense help in human cancer treatment and diagnosis.…”

Section: Uses Of Prodrugs In Cancer Therapymentioning

confidence: 99%

“…In spite of its potential uses, it shows limited prodrug uptake, dif iculty in selective targeting and gene expression. (Souza et al, 2019) They are usually inactive and are derivatives of drug molecules that undergo a chemical transformation to form active compounds. Recombinant technology in prodrugs acts as an important component that is mainly focused on attacking complex Molecular phenotypes in relevant cancer (Giang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…This combination of prodrugs is one of the best strategies used for many treatments. (Souza et al, 2019) Prodrugs generate multipurpose function and reduce the toxicity of conventional anti-cancer drugs that is done by masking as a cleavable marker. Enzyme activatable prodrugs are used in the design of anticancer prodrug and can be used as a cancer treatment strategy.…”

Section: Introductionmentioning

confidence: 99%

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Use of prodrugs in cancer therapy - A Review

Keerthana¹,

Kavitha²,

Sangeetha³

et al. 2020

ijrps

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A prodrug is a medicine that is primarily used after administration, that is metabolized into a pharmacologically active drug. A prodrug is generally a precursor form of a drug. A prodrug is used to selectively improve the drug that directly interacts with cells used in any form of treatment like chemotherapy. The drug, when taken separately, does not have much effect, whereas, a drug taken in after the administration of prodrug acts very effectively. Prodrugs are often used in the pharmaceutical field. Prodrug alters certain properties of prodrugs, such as physicochemical properties to enhance their efficacy and reduce their toxicity. The cancer cells are first injected with a gene that expresses an enzyme that has the ability to convert a non-toxic prodrug into its active cytotoxic form. Various applications of prodrugs include improving drug penetration through biological membranes, increasing site-specificity of a drug; it mainly improves patient's acceptance. Prodrugs stabilize the active drug and prevent drug metabolism. This review was written with an aim to highlight the important aspects of prodrugs and its use in cancer therapy.

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“…CPG2 also known as glucarpidase (Voraxaz ® ) is an FDA-approved bacterial enzyme breaking methotrexate (MTX) down into two noncytotoxic metabolites [21,22,23]. Due to its capacity for hydrolyzing a wide range of folate analogs, CPG2 is also able to convert non-toxic glutamated nitrogen mustard prodrugs into cytotoxic substances; hence, it is proposed as an intriguing choice for the antibody/gene-directed enzyme prodrug therapy modalities known as ADEPT and GDEPT, respectively [24,25,26]. In glucarpidase therapy, the enzyme only reduces the circulating MTX levels and has no access to the drug inside the cells.…”

Section: Introductionmentioning

confidence: 99%

Considerations on the Rational Design of Covalently Conjugated Cell-Penetrating Peptides (CPPs) for Intracellular Delivery of Proteins: A Guide to CPP Selection Using Glucarpidase as the Model Cargo Molecule

Behzadipour

Hemmati

2019

Molecules

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Access of proteins to their intracellular targets is limited by a hydrophobic barrier called the cellular membrane. Conjugation with cell-penetrating peptides (CPPs) has been shown to improve protein transduction into the cells. This conjugation can be either covalent or non-covalent, each with its unique pros and cons. The CPP-protein covalent conjugation may result in undesirable structural and functional alterations in the target protein. Therefore, we propose a systematic approach to evaluate different CPPs for covalent conjugations. This guide is presented using the carboxypeptidase G2 (CPG2) enzyme as the target protein. Seventy CPPs —out of 1155— with the highest probability of uptake efficiency were selected. These peptides were then conjugated to the N- or C-terminus of CPG2. Translational efficacy of the conjugates, robustness and thermodynamic properties of the chimera, aggregation possibility, folding rate, backbone flexibility, and aspects of in vivo administration such as protease susceptibility were predicted. The effect of the position of conjugation was evaluated using unpaired t-test (p < 0.05). It was concluded that N-terminal conjugation resulted in higher quality constructs. Seventeen CPP-CPG2/CPG2-CPP constructs were identified as the most promising. Based on this study, the bioinformatics workflow that is presented may be universally applied to any CPP-protein conjugate design.

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Prodrugs for targeted cancer therapy

Cited by 53 publications

References 156 publications

Combination Therapy of Metastatic Castration-Recurrent Prostate Cancer: Hyaluronic Acid Decorated, Cabazitaxel-Prodrug and Orlistat Co-Loaded Nano-System

Combination Therapy of Metastatic Castration-Recurrent Prostate Cancer: Hyaluronic Acid Decorated, Cabazitaxel-Prodrug and Orlistat Co-Loaded Nano-System

Use of prodrugs in cancer therapy - A Review

Considerations on the Rational Design of Covalently Conjugated Cell-Penetrating Peptides (CPPs) for Intracellular Delivery of Proteins: A Guide to CPP Selection Using Glucarpidase as the Model Cargo Molecule

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