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Efficacy of Surface-Modified PLGA Nanoparticles as a Function of Cervical Cancer Type

  • Lee B. Sims
  • Keegan C. Curry
  • Sindhu Parupalli
  • Gwynneth Horner
  • Hermann B. Frieboes
  • Jill M. Steinbach-RankinsEmail author
Research Paper
Part of the following topical collections:
  1. Nanomedicines in Cancer

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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 Words

3D cell culture cell penetrating peptide (CPP) cervical cancer nanoparticles nanotherapy 

Abbreviations

AUC

Area under the curve

C6

Coumarin 6

CPP

Cell penetrating peptide

DCM

Methylene chloride

diH2O

Deionized water

Dox

Doxorubicin

EPR

Enhanced permeability and retention

FRT

Female reproductive tract

HPV

Human papilloma virus

MDR

Multi-drug resistant

MEM

Minimum essential media

MFI

Mean fluorescence intensity

NaDC

Sodium deoxycholate

NP

Nanoparticle

o/w

Oil-in-water

PA-NHS

Palmitic acid-N-hydroxysuccinimide ester

PBS

Phosphate buffered saline

PEG

Polyethylene glycol

Pgp

P-glycoprotein

PLGA

Poly(lactic-co-glycolic) acid

PVA

Polyvinyl alcohol

RPMI

Roswell Park Memorial Institute medium

SEM

Scanning electron microscopy

Notes

Supplementary material

11095_2019_2602_MOESM1_ESM.docx (149 kb)
ESM 1 (DOCX 148 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Lee B. Sims
    • 1
  • Keegan C. Curry
    • 2
  • Sindhu Parupalli
    • 1
  • Gwynneth Horner
    • 3
  • Hermann B. Frieboes
    • 1
    • 4
    • 5
  • Jill M. Steinbach-Rankins
    • 1
    • 5
    • 6
    • 7
    Email author
  1. 1.Department of BioengineeringUniversity of LouisvilleLouisvilleUSA
  2. 2.Department of BiologyUniversity of LouisvilleLouisvilleUSA
  3. 3.School of MedicineUniversity of LouisvilleLouisvilleUSA
  4. 4.James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleUSA
  5. 5.Department of Pharmacology and ToxicologyUniversity of LouisvilleLouisvilleUSA
  6. 6.Department of Microbiology and ImmunologyUniversity of LouisvilleLouisvilleUSA
  7. 7.Center for Predictive MedicineUniversity of LouisvilleLouisvilleUSA

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