RETRACTED: Multi‐Stimuli Nanocomposite Therapeutic: Docetaxel Targeted Delivery and Synergies in Treatment of Human Breast Cancer Tumor

Abstract

To further improve the efficiencies of the established drugs, various treatment strategies, such as preparation of protein-drug conjugates and the design of nanoscale drug-carriers, are used to increase the efficacy of therapeutic agents. [6-8] Several effective nanocarrier systems were designed to deliver anti-cancer cytotoxic agents to tumor cells with high selectivity and efficacy while minimizing negative side effects. [9,10] Drug nano-carriers provide multiple advantages, such as convenient uptake and internalization, reduced drug interactions, optimized lifetime, and widened therapeutic windows. [11] In this regard, the synthetic design and applications of different types of iron oxide nanoparticles (Fe 3 O 4 NPs) have received significant attention since these NPs can be magnetically directed inside target tissues and their surface can be easily functionalized with diverse polymers and organic compounds. [12-16] Previously, we have reported several magnetic systems in micro-and nanoscale for diverse functional applications. [17-24] To further expand upon this work, we utilized one of the most commonly employed polymers, polyvinyl alcohol (PVA), to encapsulate magnetic Fe 3 O 4 NPs by virtue of its extended hydrogen bonding and to provide a selective release medium for DXL. [25] Drug molecules, such as DXL, can be incorporated into a PVA gel when polymer chains are in a shrunk state at low temperatures, and subsequently released in a target tissue upon a PVA transition into a swollen gel at 37 °C. [26] PVA features several important advantages. First is the ability to form a gel owing to multiple hydrogen bonding by OH groups. A versatile breast cancer-targeting nanocomposite therapeutic combining docetaxel (DXL), polyvinyl alcohol (PVA) network for controlled release, and silica-protected magnetic iron oxide nanoparticles (Fe 3 O 4 NPs) for targeted delivery and gold nanoparticles (AuNPs) for plasmonic photothermal therapy (PPTT) is presented in this work. First, the designed nanocomposite is magnetically directed for cancer-targeted therapy confirmed by computerized tomography (CT) scans. Second, 10% DXL by mass is loaded into PVA, a pH and temperature responsive gel, for controlled release. Third, PPTT is confirmed with Au/Fe 3 O 4 /PVA-10%DXL using a prototype circulation system and then for tumor treatment in vivo; Au/Fe 3 O 4 /PVA-10%DXL is conveniently directed and the entrapped DXL is selectively released (≈96%) via the interaction of green and near-infrared (NIR) light with the localized surface plasmon resonance of AuNPs. A 75% cell death is reported from in vitro studies with DXL doses as low as 20 µg mL −1 of Au/Fe 3 O 4 /PVA-10%DXL, and a 70% tumor growth inhibition is demonstrated by in vivo experiments with the biosafety studies confirming minimal side effects to other organs. Overall, the developed Au/Fe 3 O 4 /PVA-10%DXL has a strong potential to simultaneously enhance CT imaging contrast together with the targeted delivery of DXL.

Recent Advances in the Use of Iron–Gold Hybrid Nanoparticles for Biomedical Applications

“…Overall, the tumor inhibition was achieved by a combination of magnetically targeted delivery by iron NPs, pH and temperature-selective docetaxel release by PVA component, photothermal effect of gold NPs, and anti-tumor effects of docetaxel. This study reflects the successful report of iron–gold nanohybrids as a single system for multifunctional uses in cancer therapy [ 105 ]. In another example, Yun Quan-Li et al have covalently attached a cytotoxic agent such as methotrexate to iron–gold alloy NPs and reported that with the increase in the applied magnetic field, the release of methotrexate increased in an incremental manner [ 111 ].…”

“…Nanohybrids combining magnetic and gold nanoparticles facilitate the selective release of drugs [ 105 ] which are successfully employed for gene [ 106 ] and drug delivery applications [ 23 , 107 , 108 , 109 , 110 ]. For instance, Reza et al has reported a nanohybrid of iron oxide and gold NPs with a polymer such as PVA and cytotoxic drug such as docetaxel.…”

Plasmonic photothermal release of docetaxel by gold nanoparticles incorporated onto halloysite nanotubes with conjugated 2D8-E3 antibodies for selective cancer therapy

“…Importantly for the practical realization of the DTX@HNT/Au-SORT synergy, low temperatures of the disruption of the HNT hydrogen bonding in DTX@HNT/Au-SORT at low pH can be conveniently reached through the PPTT-heating of the AuNPs [ 6 ]. This enables facile implementation of the DTX@HNT/Au-SORT design based on the synergy of the PPTT and targeted release of DTX incorporated in HNTs.…”

“…Traditional cancer therapy relies upon the administration of cytotoxic chemical agents resulting in multiple negative side effects of chemotherapy due to the susceptibility of normal cells to this treatment [ 1 , 2 ]. Current strategies to minimize these side effects involve different approaches for targeted drug delivery to specific tissues [ 3 – 5 ], including magnetically driven transport of therapeutic agents [ 6 – 8 ], and/or incorporation of the specific biomolecules, such as aptamers [ 9 ], peptide sequences [ 10 ], and antibodies [ 11 ] onto the surface of the nanoscale carriers for selective delivery of the anti-cancer medication [ 12 , 13 ]. There are two main types of cancer cells to target: (1) cancer stem cells (CSCs) that could develop into different cell types [ 14 ], and (2) differentiated cancer cells (DCCs) that have matured into a particular form of cancer [ 15 ].…”

Magnetically recoverable catalysts for the preparation of pyridine derivatives: an overview

“…In recent decades, nanotechnology has attracted much attention in various elds. 1,2 One of the most inuential families of nanomaterials is magnetic nanoparticles, which have been extensively employed in different sciences, including drug delivery, 3 illness recognition, 4 water desalination, 5 ambiance scrubbing, 6 and chemical catalysis. 7 Recently, magnetic nanocatalysts have attracted the consideration of many researchers due to their high activity, selectivity, availability, large surface area, low toxicity, excellent reusability, and easy separation.…”