Environment-stimulated nanocarriers enabling multi-active sites for high drug encapsulation as an "on demand" drug release system

Limited active sites in polyesters hinder fabrication of multifunctional biodegradable nanocarriers for successful clinical applications. Herein, poly(malic acid) (PMA)-based biodegradable polyesters bearing large carboxyl groups in their side chains were grafted with intracellular reductive-sensiti...

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Bibliographic Details
Published in:Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2018-04, Vol.6 (15), p.2258-2273
Main Authors: Cheng, F. R, Su, T, Cao, J, Luo, X. L, Li, Li, Pu, Yuji, He, B
Format: Article
Language:English
Subjects:
Anticancer properties
Antitumor activity
Biodegradability
Biodegradation
Blood circulation
Drug delivery systems
Drug development
Dynamic stability
Fabrication
Imidazole
Intracellular
Light scattering
Monomers
Organs
Photon correlation spectroscopy
Polyester resins
Polyesters
Polyethylene glycol
Polymalic acid
Side effects
Therapeutic applications
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Summary:Limited active sites in polyesters hinder fabrication of multifunctional biodegradable nanocarriers for successful clinical applications. Herein, poly(malic acid) (PMA)-based biodegradable polyesters bearing large carboxyl groups in their side chains were grafted with intracellular reductive-sensitive polyethylene glycol and imidazole to construct bioreducible nanocarriers (PLM- g -ss-EGA). The uniform spherical shape and high stability of the PLM- g -ss-EGA nanocarriers were demonstrated by dynamic light scattering (DLS) and dissipative particle dynamics (DPD) simulations. Enhanced interaction between the monomers in this novel nanocarrier doubled its drug loading efficiency (15%) as compared to that of traditional polyester nanocarriers (5-7%). Moreover, stimulus-responsive assessment and in vitro drug release studies showed that these bioreducible nanocarriers can balance extracellular stability in blood circulation and intracellular "on demand" release. In vitro and in vivo assays have demonstrated that these bioreducible nanocarriers not only can substantially enhance antitumor efficacy as compared to insensitive micelles and even comparably to free DOX·HCl, but can also greatly reduce unwanted side effects in other organs. The encouraging anticancer efficiency of these poly(malic acid)-based nanocarriers opens a new avenue to design multifunctional biodegradable polyester drug-delivery systems. Limited active sites in polyesters hinder fabrication of multifunctional biodegradable nanocarriers for successful clinical applications.
ISSN:2050-750X
2050-7518
DOI:10.1039/c8tb00132d