Imidazoquinoline-Conjugated Degradable Coacervate Conjugate for Local Cancer Immunotherapy.
ACS Biomater Sci Eng
; 6(9): 4993-5000, 2020 09 14.
Article
em En
| MEDLINE
| ID: mdl-33455292
Strategies that can reduce the harmful side effects of potent immunomodulatory drugs are in high demand to facilitate clinical translation of the newest generation of immunotherapy. Indeed, uncontrolled triggering of the immune system can lead to life-threatening cascade reactions, such as e.g. cytokine storm. In particular, drug formulations that combine simplicity and degradability are of formidable relevance. Imidazoquinolines are an excellent example of such small molecule immunomodulatory drugs that exhibit in unformulated form a highly undesirable pharmacokinetic profile. Imidazoquinolines are potent inducers of type I interferons that are of great interest in the context of anticancer and antiviral therapy through triggering of Toll like receptors 7 and 8. In this work we aimed to alter the pharmacokinetic profile of imidazoquinolines using a simple, yet efficient, strategy that holds high potential for clinical translation. Hereto, we conjugated an imidazoquinoline to the backbone of poly(aspartate) and further formulated this into a degradable coacervate through complex coacervation with a nontoxic degradable polycation. The intrinsic TLR activity of the imidazoquinoline was well preserved and our formulation strategy offered spatial control over its biological activity in vivo.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoterapia
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
ACS Biomater Sci Eng
Ano de publicação:
2020
Tipo de documento:
Article