Hydroxyethyl Starch-Based Nanoparticles Featured with Redox-Sensitivity and Chemo-Photothermal Therapy for Synergized Tumor Eradication.

Chan Yu,Hang Hu,Zheng Li,Shaocong Wang,Chuqi Liu,Ying Wan,Xiangliang Yang

doi:10.3390/cancers11020207

Chan Yu, Hang Hu + Show 5 more

Open Access

https://doi.org/10.3390/cancers11020207

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Journal: Cancers	Publication Date: Feb 11, 2019
Citations: 18	License type: CC BY 4.0

Affiliation: Huazhong University of Science and Technology

Abstract

Chemo-photothermal combination therapy could achieve synergistically enhanced efficiency against tumors. Nanocarriers with good safety and high efficiency for chemo- photothermal therapy are pressingly needed. A new type of hydroxyethyl starch (HES) based on nanoparticles (NPs) loaded with doxorubicin (DOX) and indocyanine green (ICG) was, thus, developed in this study. DOX-loaded HES conjugates with redox-sensitivity (HES-SS-DOX) were first synthesized and they were then combined with ICG to self-assemble into HES-SS-DOX@ICG NPs with controlled compositions and sizes via collaborative interactions. The optimal HES-SS-DOX@ICG NPs had good physical and photothermal stability in aqueous media and showed high photothermal efficiency in vivo. They were able to fast release the loaded DOX in response to the redox stimulus and the applied laser irradiation. Based on the H22-tumor-bearing mouse model, these NPs were found to tendentiously accumulate inside tumors in comparison to other major organs. The HES-SS-DOX@ICG NPs together with dose-designated laser irradiation were able to fully eradicate tumors with only one injection and one single subsequent laser irradiation on the tumor site during a 14-day treatment period. In addition, they showed almost no impairment to the body. The presently developed HES-SS-DOX@ICG NPs have good in vivo safety and highly efficient anti-tumor capability. These NPs in conjugation with laser irradiation have promising potential for chemo-photothermal cancer therapy in the clinic.

Highlights

Most chemotherapeutic molecules for cancer treatment show no specificity and they are generally quickly excreted from the body by glomerular filtration or entrapped by the reticulo-endothelial system (RES) once administered intravenously
hydroxyethyl starch (HES)-SS-DOX@Indocyanine green (ICG) NPs were prepared using a facile but highly effective method based on the mutual interactions between DOX and ICG
A series of HES-SS-DOX@ICG NPs was prepared to screen out appropriate parameters for them

Summary

Introduction

Most chemotherapeutic molecules for cancer treatment show no specificity and they are generally quickly excreted from the body by glomerular filtration or entrapped by the reticulo-endothelial system (RES) once administered intravenously. As a result, they commonly show limited efficiency with low bioavailability while leading to various side effects [1]. Cancers 2019, 11, 207 for drug-delivery are generally engineered by attaching the drug molecules to water-soluble or hydrophilic polymers through cleavable spacers [2,3], and the employed polymers usually have their molecular weight higher than the limit of the renal threshold, which enables the resulting conjugates to preferentially deliver drugs toward tumors via the prolonged circulation and the enhanced permeability and retention (EPR) effect [4]. Many polymer-conjugates release the loaded drugs by hydrolysis of spacers, which often causes their poor stability while resulting in unwanted side effects on normal cells [6]

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