Oleic Acid Copolymer as A Novel Upconversion Nanomaterial to Make Doxorubicin-Loaded Nanomicelles with Dual Responsiveness to pH and NIR.

Jin Zhang,Chuanqing Huang,Zeyu Liu,Xiaoyue Tang,Yong Ye

doi:10.3390/pharmaceutics12070680

Jin Zhang, Chuanqing Huang + Show 3 more

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https://doi.org/10.3390/pharmaceutics12070680

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Journal: Pharmaceutics	Publication Date: Jul 20, 2020
Citations: 6	License type: CC BY 4.0

Affiliation: South China University of Technology

Abstract

Oleic acid (OA) as main component of plant oil is an important solvent but seldom used in the nanocarrier of anticancer drugs because of strong hydrophobicity and little drug release. In order to develop a new type of OA nanomaterial with dual responses to pH and near infrared light (NIR) to achieve the intelligent delivery of anticancer drugs. The novel OA copolymer (mPEG-PEI-(NBS, OA)) was synthesized by grafting OA and o-nitrobenzyl succinate (NBS) onto mPEGylated polyethyleneimine (mPEG-PEI) by amidation reaction. It was further conjugated with NaYF4:Yb3+/Er3+ nanoparticles, and encapsulated doxorubicin (DOX) through self-assembly to make upconversion nanomicelles with dual response to pH and NIR. Drug release behavior of DOX, physicochemical characteristics of the nanomicelles were evaluated, along with its cytotoxic profile, as well as the degree of cellular uptake in A549 cells. The encapsulation efficiency and drug loading capacity of DOX in the nanomicelles were 73.84% ± 0.58% and 4.62% ± 0.28%, respectively, and the encapsulated DOX was quickly released in an acidic environment exposed to irradiation at 980 nm. The blank nanomicelles exhibited low cytotoxicity and excellent biocompatibility by MTT assay against A549 cells. The DOX-loaded nanomicelles showed remarkable cytotoxicity to A549 cells under NIR, and promoted the cellular uptake of DOX into the cytoplasm and nucleus of cancer cells. OA copolymer can effectively deliver DOX to cancer cells and achieve tumor targeting through a dual response to pH and NIR.

Highlights

Oleic acid (OA) as a natural compound widely exists in plant oil such as Camellia seed oil, which is extracted from seeds of Camellia oleifera Abel and contain OA above 90% [1,2]
The results indicate that DOX is successfully loaded and the methoxyl poly ethylene glycol (mPEG)-PEI-(NBS, OA) upconversion nanomicelles can be used as nano delivery vehicle for DOX in drug delivery systems
The OA copolymer mPEG-PEI-(NBS, OA) conjugate was successfully synthesized by grafting hydrophobic OA onto hydrophilic mPEG-PEI and interfacing with photosensitive nitrobenzyl succinate (NBS) and NaYF4:Yb3+/Er3+ nanoparticles

Summary

Introduction

Oleic acid (OA) as a natural compound widely exists in plant oil such as Camellia seed oil, which is extracted from seeds of Camellia oleifera Abel and contain OA above 90% [1,2]. OA has good biodegradability and biosafety, and can be used as solvent for drug delivery [7] It can enhance the stability of anticancer drugs, promote the entry of anticancer drugs into cells, inhibit the metastasis of cancer and the expression of oncogenes, and increase the sensitivity of anticancer drugs to chemotherapy. It has natural tumor-targeting properties, because OA can increase the intake of fatty acids in tumors as a source of nutrition, and has great potential in tumor treatment [5,8]. On the basis of OA pharmacological activities, it is meaningful to design OA drug carriers with controlled release at the tumor site

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Conclusion