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

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.

High Drug Capacity Doxorubicin-Loaded Iron Oxide Nanocomposites for Cancer Therapy

“…Several types of widely used surfactants were chosen to protect and impart surface properties. Among them are the amphiphilic polyethylene glycol 2000 (PEG 2000) [16,25,53], hydrophobic anionic oleic acid (OA) [67], and Tween (Tw) family [20,68].…”

Composite Hydrogel with Oleic Acid-Grafted Mesoporous Silica Nanoparticles for Enhanced Topical Delivery of Doxorubicin

“…The antiproliferative effects of OA have also been shown in experiments with other tumor cell lines, originating from low metastatic breast (MCF-7) and gastric (SGC7901) carcinomas [ 79 ]. The potential mechanisms by which oleic acid functionalization improves the cytotoxic effects of doxorubicin could be related to improved cellular uptake [ 80 ] and the propensity of OA to decrease the expression of oncogenes [ 81 ], which are responsible for A-431 cell survival, interfere with lipid metabolism and affect autophagy [ 82 ]. Chronic fatty acid intake has been shown to be tumorigenic in some occasions, and there should be careful benefit-risk assessment when specific therapeutic applications are designed [ 83 , 84 ].…”

Opportunities and Challenges of Switchable Materials for Pharmaceutical Use

“…NB moieties were also repetitively investigated as linkers in amphiphilic molecules such as in polymersome shells (Figure 8A) [99,100], which disassociated upon NB cleavage and released their payload. The dissociation of vesicles can also be realized by pH-dependent charge repulsion after the photoinduced removal of NB-based moieties (Figure 8B) [101]. Another concept is to use physical interactions of drug molecules with NB for their retention, e.g., in microgels, where the cleavage of NB leads to increased diffusivity of the drug and the NB degradation product (see above for comment on potential toxicity) out of the gel [102].…”