Distribution of PLGA-modified nanoparticles in 3D cell culture models of hypo-vascularized tumor tissue

Journal of Nanobiotechnology

Research

Lee B. Sims¹  Maya K. Huss¹  Jill M. Steinbach-Rankins²  Hermann B. Frieboes³ 

[1] Department of Bioengineering, University of Louisville, 505 S. Hancock, CTRB 623, 40208, Louisville, KY, USA;Department of Bioengineering, University of Louisville, 505 S. Hancock, CTRB 623, 40208, Louisville, KY, USA;Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA;Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA;Center for Predictive Medicine, University of Louisville, Louisville, KY, USA;Department of Bioengineering, University of Louisville, 505 S. Hancock, CTRB 623, 40208, Louisville, KY, USA;James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA;Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA;

关键词: Nanoparticles;    Cell penetrating peptide (CPP);    Cervical cancer;    Nanoparticle transport;    Tumor vascularization;    3D cell culture;    Tumor spheroid;   

DOI  :  10.1186/s12951-017-0298-x

 received in 2017-06-17, accepted in 2017-09-23,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAdvanced stage cancer treatments are often invasive and painful—typically comprised of surgery, chemotherapy, and/or radiation treatment. Low transport efficiency during systemic chemotherapy may require high chemotherapeutic doses to effectively target cancerous tissue, resulting in systemic toxicity. Nanotherapeutic platforms have been proposed as an alternative to more safely and effectively deliver therapeutic agents directly to tumor sites. However, cellular internalization and tumor penetration are often diametrically opposed, with limited access to tumor regions distal from vasculature, due to irregular tissue morphologies. To address these transport challenges, nanoparticles (NPs) are often surface-modified with ligands to enhance transport and longevity after localized or systemic administration. Here, we evaluate stealth polyethylene–glycol (PEG), cell-penetrating (MPG), and CPP-stealth (MPG/PEG) poly(lactic-co-glycolic-acid) (PLGA) NP co-treatment strategies in 3D cell culture representing hypo-vascularized tissue.ResultsSmaller, more regularly-shaped avascular tissue was generated using the hanging drop (HD) method, while more irregularly-shaped masses were formed with the liquid overlay (LO) technique. To compare NP distribution differences within the same type of tissue as a function of different cancer types, we selected HeLa, cervical epithelial adenocarcinoma cells; CaSki, cervical epidermoid carcinoma cells; and SiHa, grade II cervical squamous cell carcinoma cells. In HD tumors, enhanced distribution relative to unmodified NPs was measured for MPG and PEG NPs in HeLa, and for all modified NPs in SiHa spheroids. In LO tumors, the greatest distribution was observed for MPG and MPG/PEG NPs in HeLa, and for PEG and MPG/PEG NPs in SiHa spheroids.ConclusionsPre-clinical evaluation of PLGA-modified NP distribution into hypo-vascularized tumor tissue may benefit from considering tissue morphology in addition to cancer type.

【 授权许可】

CC BY   
© The Author(s) 2017