Hyaluronic acid-drug conjugate modified core-shell MOFs as pH responsive nanoplatform for multimodal therapy of glioblastoma

Pandey, Abhijeet and Kulkarni, Sanjay and Nannuri, Shivanand H and George, Sajan D and Mutalik, Srinivas (2020) Hyaluronic acid-drug conjugate modified core-shell MOFs as pH responsive nanoplatform for multimodal therapy of glioblastoma. International Journal of Pharmaceutics, 588. pp. 1-16. ISSN 0378-5173

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Abstract

Multimodal therapeutic approach has been gaining lot of attention for effective therapy of cancer. In the present work, a novel and unique pH responsive nanoplatform have been developed for multimodal therapy of glioblastoma using protein, biopolymer and MOFs. Lactoferrin (Lf) has been used as protein matrix for loading titanocene which was then enclosed in ZIF-8 framework along with 5-FU (ZIF-8@Lf-TC). The ZIF-8 was further coated with Lenalidomide-HA conjugate linked via hydrazone linkage (LND-HA@ZIF-8@Lf-TC). The developed nanocomposite was extensively characterized using spectroscopic, x-ray and electron microscopic techniques.The nanocomposites were evaluated for pH responsive drug release, stability, bio-interaction, and haemocompatibility which confirmed pH responsive nature of nanocomposite, stability and absence of any significant interaction with biomolecules. In obtained results for in vitro cell line studies performed in U87MG and RAW264.7 cells demonstrated enhanced cell cytotoxicity against cancer cells which was further supported by results of cellular ROS generation and surface ROS generation by nanocomposites. The Zinc and Lf mediated disruption of intracellular IL-6 and TNFα levels was observed with synthesized nanocomposites. They demonstrated pH responsive release of 5-FU and LND along with sustained release of both drugs in simulated medium.The LND-HA@ZIF- @Lf-TC demonstrated superior cell growth supressing ability compared to ZIF-8@Lf-TC and ZIF-8. The nanocomposites were stable in biomimicking environment as well as did not show any significant interaction with RBC, plasma or CSF. The overall results suggest that LND-HA@ZIF-8@Lf-TC can be explored as promising platform for dual drug delivery mediated multimodal therapy of cancer

Item Type: Article
Uncontrolled Keywords: Hyaluronic acid-drug conjugate; Lactoferrin nanoparticles; Titanocene; ZIF-8,Core-shell MOFs
Subjects: Departments at MU > Atomic Molecular Physics
Pharmacy > MCOPS Manipal > Pharmaceutics
Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 03 Dec 2020 09:04
Last Modified: 03 Dec 2020 09:04
URI: http://eprints.manipal.edu/id/eprint/156061

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