Magnetic particle anchored reduction and pH responsive nanogel for enhanced intracellular drug delivery

• Published in: European polymer journal 2020-04, Vol.129, p.109638, Article 109638
• Main Authors: Mandal, Pijush, Panja, Sudipta, Banerjee, Sovan Lal, Ghorai, Sanjoy Kumar, Maji, Somnath, Maiti, Tapas Kumar, Chattopadhyay, Santanu
• Format: Article
• Language: English
• Subjects: Biomolecules; Block copolymers; Cancer therapies; Crosslinking; Drug delivery systems; Esterification; Magnetic fields; Magnetic nanoparticles; Nanogel; Nanoparticles; Stimuli; Triple responsive
• ISSN: 0014-3057; 1873-1945
• DOI: 10.1016/j.eurpolymj.2020.109638

[Display omitted] •A triple-responsive (pH, magneto and redox) nanogel has been fabricated.•A star-shaped amphiphilic block copolymer has been synthesized.•Surface modified Fe3O4 nanoparticle has been incorporated within the polymer nanogel.•Doxorubicin loaded nanogels are used to sustain delivery of the drug to the cancer cells. The controlled delivery of drugs towards the cancerous cell is still an unresolved issue in the area of cancer cell targeted drug delivery. To resolve the issue, in this work, a triple-responsive (pH, magnetic field and redox) nanogel has been fabricated to potentially deliver the anticancer drug (DOX) to the cancerous cell. The nanogel has been fabricated by esterification reaction between the ‘-COOH’ group of the pre-synthesized amphiphilic tetra-armed block copolymer, pentaerythritol-poly(ε-caprolactone)-b-polyacrylic (Pe-PCL-b-PAA) and ‘-OH’ group of the redox-responsive crosslinker, 2-hydroxyethyl disulfide. The nanogels are further ornamented with aminosilane coated magnetic nanoparticles to impart the magnetic field responsive characteristic. The spherically shaped nanogel (size 120 nm) ensures the long circulation half-life in the bloodstream. The drug release profile under different stimuli such as pH, magnetic field and redox environment explored a new way of controlled drug release in a more promising manner under the synergistic participation of all three stimuli. It has been observed that the multi-stimuli responsive nanogel not only boost up the cell uptake process but also dramatically enhance the drug release rate up to 65% within 1 h under the environment of multiple stimuli (acidic pH 5, redox (10 mM GSH) and in the presence of dynamic magnetic field. Precisely, the acidic pH and reducing micro-environment of cancer affected cells are expected to act as an internal stimulus, whereas magnetic force can be maneuverer as an external stimulus in the proposed sub-structure of the nanogels. In a nut-shell, this kind of multi-responsive nanogel can pave a new direction in the area of controlled and targeted delivery of anticancer drugs or other biomolecules.