Tumor-mesoporous silica nanoparticle interactions following intraperitoneal delivery for targeting peritoneal metastasis

JOURNAL OF CONTROLLED RELEASE

卷:328

Article

Hargrove, Derek¹  Liang, Brian²  Kashfi-Sadabad, Raana^1,5  Joshi, Gaurav N.^1,6  Gonzalez-Fajardo, Laura¹  Glass, Sterling¹  Jay, Michael³  Salner, Andrew⁴  Lu, Xiuling¹ 

[1] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA

[2] Univ Connecticut, Sch Med, Storrs, CT 06268 USA

[3] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27515 USA

[4] Hartford Hosp, Dept Radiat Oncol, Helen & Harrry Gray Canc Ctr, Hartford, CT USA

[5] Stanford Univ, Sch Med, Dept Otolaryngol & Head & Neck Surg, Palo Alto, CA 94304 USA

[6] Emory Univ, Sch Med, Integrated Cellular Imaging ICI Core, Atlanta, GA 30322 USA

关键词: Nanoparticle;    Tumor microenvironment;    Surface interaction;    Peritoneal metastasis;    Targeting;   

DOI  :  10.1016/j.jconrel.2020.11.003

来源: Elsevier

【 摘 要 】

The use of intraperitoneal administration of nanoparticles has been reported to facilitate higher concentrations of nanoparticles in metastatic peritoneal tumors. While this strategy is appealing for limiting systemic exposure of nanocarrier delivered toxic cargoes and increasing nanoparticle concentrations in avascular peritoneal tumors, little is known about the mechanism of nanoparticle accumulation on tumor tissues and currently, no nanoparticle-based product has been approved for intraperitoneal delivery. Here, we investigated the nanoparticle-specific characteristics that led to increased peritoneal tumor accumulation using MCM-41 type mesoporous silica nanoparticles as our model system. We also investigated the components of the peritoneal tumor stroma that facilitated nanoparticle-tumor interaction. The tumor extracellular matrix is the main factor driving these interactions, specifically the interaction of nanoparticles with collagen. Upon disruption of the collagen matrix, nanoparticle accumulation was reduced by 50%. It is also notable that the incorporation of targeting ligands did not increase overall tumor accumulation in vivo while it significantly increased nanoparticle accumulation in vitro. The use of other particle chemistries did not grossly affect the tumor targetability, but additional concerns arose when those tested particles exhibited significant systemic exposure. Mesoporous silica nanoparticles are advantageous for intraperitoneal administration for the treatment of peritoneal metastasis due to their physical stability, tumor targetability, strong interaction with the collagen matrix, and extended peritoneal residence time. Maximizing nanoparticle interaction with the tumor extracellular matrix is critical for developing strategies to deliver emerging therapeutics for peritoneal cancer treatment using nanocarriers.

【 授权许可】

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