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

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.

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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

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Correspondence to Jill M. Steinbach-Rankins.

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Sims, L.B., Curry, K.C., Parupalli, S. et al. Efficacy of Surface-Modified PLGA Nanoparticles as a Function of Cervical Cancer Type. Pharm Res 36, 66 (2019). https://doi.org/10.1007/s11095-019-2602-y

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  • DOI: https://doi.org/10.1007/s11095-019-2602-y

Key Words

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