Hierarchical drug release designed Au @PDA-PEG-MTX NPs for targeted delivery to breast cancer with combined photothermal-chemotherapy

Abstract

Breast cancer (BC) is the most frequently diagnosed cancer with a low survival rate and one of the major causes of cancer-related death. Methotrexate (MTX) is an anti-tumor drug used in the treatment of BC. Poor dispersion in water and toxic side effects limit its clinical application. Gold nanoparticles (AuNPs), owing to their specific structures and unique biological and physiochemical properties, have emerged as potential vehicles for tumor targeting, bioimaging and cancer therapy. An innovative nano drug-loading system (Au @PDA-PEG-MTX NPs) was prepared for targeted treatment of BC. Au @PDA-PEG-MTX NPs under near infra-red region (NIR) irradiation showed effective photothermal therapy against MDA-MB-231 human BC cells growth in vitro by inducing apoptosis through triggering reactive oxygen species (ROS) overproduction and generating excessive heat. In vivo studies revealed deep penetration ability of Au @PDA-PEG-MTX NPs under NIR irradiation to find application in cancer-targeted fluorescence imaging, and exhibited effective photothermal therapy against BC xenograft growth by inducing apoptosis. Histopathological analysis, cellular uptake, cytotoxicity assay, and apoptosis experiments indicated that Au @PDA-PEG-MTX NPs possessed a good therapeutic effect with high biocompatibility and fewer side effects. This Au NPs drug-loading system achieved specific targeting of MTX to BC cells by surface functionalisation, fluorescence imaging under laser irradiation, combined photothermal-chemotherapy, and pH- and NIR- triggered hierarchical drug release.

Melanin-like nanoparticles: advances in surface modification and tumour photothermal therapy

“…PDA comprise hydroxyl, carboxyl, phenolic, and amine groups, which offer numerous potential binding or biosorption sites for metal ions to be deposited on the surface of virtually any substance. They are able to graft drugs, bioactive molecules, and polymers onto its surface via addition reactions [ 72 ], photoinitiated polymerization [ 73 ], free radical polymerization [ 73 ], single-electron transfer activated radical polymerization (SET-LPR) [ 74 ], surface-initiated atom transfer radical polymerization (SI-ATRP) [ 75 ], and reversible addition-rupture chain transfer polymerization (RAFT) [ 76 ], thereby enhancing the dispersibility and biocompatibility of PDA or imparting them with slow or controlled release properties.…”

“…Addition reactions are a common method for modifying the surface of PDAs, and PDA films can be immobilized with amino- and thiol-containing compounds via Michael addition reactions or Schiff base reactions. For instance, -SH or -NH 2 capped polyethylene glycols (PEG-SH or PEG-NH 2 ) are immobilized on the surface of PDA films by Michael addition reactions, and nanodrugs modified by this step decrease the recognition and destruction of nanoparticles by the reticuloendothelial system (RES) and increase circulation time [ 55 , 77 – 80 ]. In addition, using this method, various peptide or ligand molecules can be functionalized onto the surface of PDA-based nanoparticles to enhance tumor cell uptake.…”

Research Progress on Nanoparticles-Based CRISPR/Cas9 System for Targeted Therapy of Tumors

“…On the other hand, NPs show good biocompatibility and low side effects because of their ultrasmall diameter and environmental basic elements [ 36 ]. Numerous studies and clinical trials have displayed that NPs can be safely used in vitro and in vivo up to now [ 37 , 38 ]. NPs can be taken up by cells through endocytosis to deliver CRISPR/Cas9 cargo, so the use of targeted NPs with multifunctional modification that are appropriate for cancer treatment have attracted the attention of researchers [ 39 ].…”

Inspirations of Cobalt Oxide Nanoparticle Based Anticancer Therapeutics

“…Since the 1980s, nanomaterials have been studied as functional drug carriers by enhancing the targeting effects and anti-tumor effects of drugs in vivo. After more than 30 years of exploration, it has been discovered that some nanomaterials based on nanomedicines have the advantages of high biocompatibility, high targeting and low toxicity for cancer treatment [52]. While many metal oxide nanoparticles have been proved to have anticancer activity [53], cobalt oxide nanomaterials have also been recently reported for their anticancer activities, which indicated their potential for anticancer treatment.…”