Paclitaxel and etoposide co-loaded polymeric nanoparticles for the effective combination therapy against human osteosarcoma.

Bing Wang,Ming Xu,Xiu-Chun Yu,Song-Feng Xu

doi:10.1186/s12951-015-0086-4

Bing Wang, Ming Xu + Show 2 more

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https://doi.org/10.1186/s12951-015-0086-4

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Abstract

BackgroundThe combination of chemotherapeutic drugs with different pharmacological action has emerged as a promising therapeutic strategy in the treatment of cancers. Present study examines the antitumor potential of paclitaxel (PTX) and etoposide (ETP)-loaded PLGA nanoparticles for the treatment of osteosarcoma.ResultsThe resulting drug-loaded PLGA NP exhibited a nanosize dimension with uniform spherical morphology. The NP exhibited a sustained release profile for both PTX and ETP throughout the study period without any sign of initial burst release. The combinational drug-loaded PLGA NP enhanced the cytotoxic effect in MG63 and Saos-2 osteosarcoma cell lines, in comparison to either native drug alone or in cocktail combinations. Additionally, NPs showed an appreciable uptake in MG63 cells in a time-based manner. Co-delivery of anticancer drugs resulted in enhanced cell cycle arrest and cell apoptosis. The results clearly showed that combinational drugs remarkably improved the therapeutic index of chemotherapeutic drugs. The greater inhibitory effect of nanoparticle combination would be of great advantage during systemic cancer therapy.ConclusionTaken together, our study demonstrated that PTX-ETP/PLGA NP based combination therapy holds significant potential towards the treatment of osteosarcoma.

Highlights

The combination of chemotherapeutic drugs with different pharmacological action has emerged as a promising therapeutic strategy in the treatment of cancers
Cancer therapy based on single drug remains unsatisfying due to the complex microenvironment of cancer cells along with the drug resistance mechanisms [7]
In order to prolong the systemic blood circulation time, poly(lactic-co-glycolic acid) (PLGA) NP was surface modified with Polyethylene Glycol (PEG) moiety that can endow the antifouling effect (Figure 1A)

Summary

Introduction

The combination of chemotherapeutic drugs with different pharmacological action has emerged as a promising therapeutic strategy in the treatment of cancers. Present study examines the antitumor potential of paclitaxel (PTX) and etoposide (ETP)-loaded PLGA nanoparticles for the treatment of osteosarcoma. Osteosarcoma (OS) is one of the most prevalent malignant bone cancers affecting adolescents aged between 10 and 24 years [1]. Children and adolescent constitutes 60% of overall bone tumor cases in past 2 decades [2]. Significant progress have been made in the treatment of OS (5 year survival rate to 65%), metastatic cancer which constitutes to only 20% survival rate is a big cause of concern [3]. The standard treatment protocol for this disease mainly includes surgery and conventional chemotherapy. Single drug regimen based chemotherapy is the mainstay treatment for OS. Despite great strides in OS treatment, no substantial improvement in OS therapy has taken place and remains elusive [5,6]

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