Journal article
Slippery Nanoparticles as a Diffusion Platform for Mucin Producing Gastrointestinal Tumors
Annals of surgical oncology, v 27(1), pp 76-84
01 Jan 2020
PMID: 31187366
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background. Treatment failure in pseudomyxoma peritonei (PMP) is partly attributed to the ineffective delivery of therapeutics through dense mucinous tumor barriers. We modified the surface of Poly (lactic-co-glycolic acid)-b-polyethylene glycol (PLGA-PEG-NPs) with a low-density, second PEG layer (PLGA-TPEG-NPs-20) to reduce their binding affinity to proteins and improve diffusion through mucin.
Methods. Nanoprecipitation was used to fabricate PLGA-PEG-NPs. To construct the second PEG layer of PLGA-TPEG-NPs-20, PEG-Thiol was conjugated to PLGA-PEG-NPs composed of 80% methoxy PLGA-PEG and 20% of PLGA-PEG-Maleimide. DiD-labeled nanoparticles (NPs) were added to the inner well of a trans-well system containing cultured LS174T or human PMP tissue. Diffusion of NPs was measured via fluorescence signal in the bottom well. In an ex vivo rat model, small intestine was treated with DiD-labeled NPs. In an in vivo murine LS174T subcutaneous tumor model, Nu/Nu nude mice received supratumoral injections (subcutaneous injection above the tumor) of DiD-labeled NPs. Thirty minutes after injection, mice were sacrificed, and tumors were collected. All tissue was cryosectioned, mounted with DAPI-containing media, and inspected via confocal microscopy.
Results. Diffusion profiles of NPs through PMP and cultured LS174T cells were generated. PLGA-TPEG-NPs-20 diffused faster with similar to 100% penetration versus PLGA-PEG-NPs with similar to 40% penetration after 8 h. Increased diffusion of PLGA-TPEG-NPs-20 was further observed in ex vivo rat small intestine as evidenced by elevated luminal NP fluorescence signal on the luminal surface. Subcutaneous LS174T tumors treated with PLGA-TPEG-NPs-20 demonstrated greater diffusion of NPs, showing homogenous fluorescence signal throughout the tumor.
Conclusions. PLGA-TPEG-NPs-20 can be an effective mucin penetrating drug delivery system.
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Details
- Title
- Slippery Nanoparticles as a Diffusion Platform for Mucin Producing Gastrointestinal Tumors
- Creators
- Marian Khalili - Drexel UniversityHao Zhou - Drexel UniversityAnusha Thadi - Drexel UniversityLynsey Daniels - Drexel UniversityZhiyuan Fan - Drexel UniversityWilliam F. Morano - Drexel UniversityJoanne Ang - Drexel UniversityEve Goldstein - Drexel UniversityBoris Polyak - Drexel UniversityBeth C. Mapow - Drexel UniversityHao Cheng - Drexel UniversityWilbur B. Bowne - Drexel University
- Publication Details
- Annals of surgical oncology, v 27(1), pp 76-84
- Publisher
- Springer Nature
- Number of pages
- 9
- Grant note
- 260696 / National Organization of Rare Disorders (NORD) through Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Materials Science and Engineering; Surgery
- Web of Science ID
- WOS:000509111500014
- Scopus ID
- 2-s2.0-85067387623
- Other Identifier
- 991019168327304721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Oncology
- Surgery