Efficacy of Surface-Modified PLGA Nanoparticles as a Function of Cervical Cancer Type
Hypovascularization of cervical tumors, coupled with intrinsic and acquired drug resistance, has contributed to marginal therapeutic outcomes by hindering chemotherapeutic transport and efficacy. Recently, the heterogeneous penetration and distribution of cell penetrating peptide (CPP, here MPG) and polyethylene glycol (PEG) modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were evaluated as a function of tumor type and morphology in cervical cancer spheroids modeling hypovascularized tumor nodules. Building upon this work, this study investigates the efficacy imparted by surface-modified Doxorubicin-loaded NPs transported into hypovascularized tissue.
NP efficacy was measured in HeLa, CaSki, and SiHa cells. NP internalization and association, and associated cell viability, were determined in monolayer and spheroid models.
MPG and PEG-NP co-treatment was most efficacious in HeLa cells, while PEG NPs were most efficacious in CaSki cells. NP surface-modifications were unable to improve efficacy, relative to unmodified NPs, in SiHa cells.
The results highlight the dependence of efficacy on tumor type and the associated microenvironment. The results further relate previous NP transport studies to efficacy, as a function of surface-modification and cell type. Longer-term, this information may help guide the design of NP-mediated strategies to maximize efficacy based on patient-specific cervical tumor origin and characteristics.
Key Words3D cell culture cell penetrating peptide (CPP) cervical cancer nanoparticles nanotherapy
Area under the curve
Cell penetrating peptide
Enhanced permeability and retention
Female reproductive tract
Human papilloma virus
Minimum essential media
Mean fluorescence intensity
Palmitic acid-N-hydroxysuccinimide ester
Phosphate buffered saline
Roswell Park Memorial Institute medium
Scanning electron microscopy
- 12.Gutierrez-Iglesias G, Hurtado Y, Palma-Lara I, Lopez-Marure R. Resistance to the antiproliferative effect induced by a short-chain ceramide is associated with an increase of glucosylceramide synthase, P-glycoprotein, and multidrug-resistance gene-1 in cervical cancer cells. Cancer Chemother Pharmacol. 2014;74(4):809–17.PubMedCrossRefGoogle Scholar
- 14.Grigore ME. Organic and inorganic Nano-Systems used in Cancer treatment. Journal of Medical Research and Health Education. 2017;1.Google Scholar
- 32.Beáta Tóth PK, Rémi Magnan. Membrane transporters and transporter substrates as biomarkers for drug pharmacokinetics, pharmacodynamics, and toxicity/adverse events. In: Press A, editor. Biomarkers in Toxicology: Academic Press; 2014. p. 947–963.Google Scholar
- 40.England CG, Gobin AM, Frieboes HB. Evaluation of uptake and distribution of gold nanoparticles in solid tumors. Eur Phys J Plus. 2015;130(11).Google Scholar