Polymer-drug conjugates as modulators of cellular apoptosis

Vicent, Marı́a J.

doi:10.1208/aapsj0902022

Cited by 42 publications

(26 citation statements)

References 67 publications

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“…In addition, new promising lines of research are being followed to achieve active targeting by polymer-drug conjugates that inhibit specific kinases [186][187][188][189], activate apoptosis [190][191][192] or decrease angiogenesis [183][184][185][193][194][195][196], being all these lines of research in preclinical status, except for a polyacetal-fumagillin (antiangiogenic) conjugate (XMT-1107) which is under a phase I trial [18,197].…”

Section: Polymer Therapeuticsmentioning

confidence: 99%

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Pérez-Herrero

Fernández‐Medarde

2015

European Journal of Pharmaceutics and Biopharmaceutics

1,396

754

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Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vasculatization and, in time, adquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastasic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, like the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic Código de campo cambiado

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Section: Polymer Therapeuticsmentioning

confidence: 99%

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Pérez-Herrero

Fernández‐Medarde

2015

European Journal of Pharmaceutics and Biopharmaceutics

1,396

754

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“…This drug induces apoptosis competing with sphingosine kinase (SpK), a key regulator of tumour angiogenesis [95]. Although pro-apoptotic approaches are related with cancer therapy, anti-apoptotic strategies have also applications in regenerative medicine [96]. Vicent and coworkers designed the first anti-apoptotic polymeric nanomedicine: a PGA-based Apaf-1 inhibitor conjugate [97,98], which has shown to promote regeneration in the course of inflammation-induced tissue injury [99].…”

Section: Drug Deliverymentioning

confidence: 99%

Peptide-Based Polymer Therapeutics

2014

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Abstract:Polypeptides are envisaged to achieve a major impact on a number of different relevant areas such as biomedicine and biotechnology. Acquired knowledge and the increasing interest on amino acids, peptides and proteins is establishing a large panel of these biopolymers whose physical, chemical and biological properties are ruled by their controlled sequences and composition. Polymer therapeutics has helped to establish these polypeptide-based constructs as polymeric nanomedicines for different applications, such as disease treatment and diagnostics. Herein, we provide an overview of the advantages of these systems and the main methodologies for their synthesis, highlighting the different polypeptide architectures and the current research towards clinical applications.

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“…Such antagonism impairs mitochondrial-mediated apoptosis, which is associated with many neurodegenerative diseases 42 . Introducing conformational constraint 43 and conjugation of the peptoid to cell penetrating peptides 44 or a polymeric carrier 45 enhance the effectiveness of these peptoids. Thus, peptoids can target neuroprotective pathways relevant to neurodegenerative diseases.…”

Section: Peptoids As Neuroprotective Agentsmentioning

confidence: 99%

Peptoids: Emerging Therapeutics for Neurodegeneration

Moss¹

2017

J Neurol Neuromedicine

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In recent decades, the increasing prevalence of age-associated neurodegenerative diseases has underscored the need for targeted therapeutic strategies and novel diagnostics. Peptide-based neurotherapeutics offer high specificity and tolerability but are limited by proteolytic degradation in vivo. Peptoids, or N-substituted glycines, are versatile peptidomimetics that evade proteolytic degradation yet maintain many qualities that render peptides attractive neurotherapeutic candidates. These molecules may be engineered to their application through modifications that enhance structural stability and reactivity and can withstand various physiological stressors to retain their intended function within anomalous microenvironments.Peptoids generally demonstrate greater cellular permeability than their corresponding peptides, are less immunogenic, and can be administered intranasally, all properties that enhance their potential as neurotherapeutics. Peptoids have primarily been explored as aggregation inhibitors to prevent the deleterious protein plaque deposition associated with several neurodegenerative disorders. However, novel research has uncovered the potential of peptoids toward additional neurotherapeutic applications. Peptoids can modulate cell signaling pathways involved in axonal function and current modulation and can block cell signaling events associated with apoptosis. In addition, these peptidomimetics are able to function as anti-inflammatory agents via multiple mechanisms. Moreover, the versatility and low cost of peptoids render them ideal instruments in biomarker detection, discovery, and imaging. This mini-review explores these diverse applications of peptoids within the context of neurodegenerative disease.

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Polymer-drug conjugates as modulators of cellular apoptosis

Cited by 42 publications

References 67 publications

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Peptide-Based Polymer Therapeutics

Peptoids: Emerging Therapeutics for Neurodegeneration

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