Layer‐by‐layer nanoparticles for novel delivery of cisplatin and PARP inhibitors for platinum‐based drug resistance therapy in ovarian cancer
Name
btm2.10131.pdf
Description
Published version
Size
5.28 MB
Format
Unknown
Checksum (MD5)
1e7fe21604531b2c13ef760ac01a1d09
Author(s)
Mensah, Lawrence B.
Morton, Stephen W.
Li, Jiahe
Xiao, Haihua
Quadir, Mohiuddin A.
Elias, Kevin M.
Penn, Emily
Richson, Aysen K.
Ghoroghchian, Paiman Peter
Liu, Joyce
Date Issued
May 2019
Journal
Bioengineering & Translational Medicine
Publisher
Wiley
Version
Final published version
Abstract
Advanced staged high-grade serous ovarian cancer (HGSOC) is the leading cause of gynecological cancer death in the developed world, with 5-year survival rates of only 25-30% due to late-stage diagnosis and the shortcomings of platinum-based therapies. A Phase I clinical trial of a combination of free cisplatin and poly(ADP-ribose) polymerase inhibitors (PARPis) showed therapeutic benefit for HGSOC. In this study, we address the challenge of resistance to platinum-based therapy by developing a targeted delivery approach. Novel electrostatic layer-by-layer (LbL) liposomal nanoparticles (NPs) with a terminal hyaluronic acid layer that facilitates CD44 receptor targeting are designed for selective targeting of HGSOC cells; the liposomes can be formulated to contain both cisplatin and the PARPi drug within the liposomal core and bilayer. The therapeutic effectiveness of LbL NP-encapsulated cisplatin and PARPi alone and in combination was compared with the corresponding free drugs in luciferase and CD44-expressing OVCAR8 orthotopic xenografts in female nude mice. The NPs exhibited prolonged blood circulation half-life, mechanistic staged drug release and targeted codelivery of the therapeutic agents to HGSOC cells. Moreover, compared to the free drugs, the NPs resulted in significantly reduced tumor metastasis, extended survival, and moderated systemic toxicity.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/btm2.10131
