Gold Nanorod-Based Nanohybrids for Combinatorial Therapeutics

Abstract

In this work, multifunctional nanocarriers consisting of poly(sodium-4-styrenesulfonate) (PSS)/doxorubicin (DOXO)/poly-l-lysine hydrobromide (PLL)/hyaluronic acid (HA)-coated and (PSS/DOXO/PLL)2/HA-coated gold nanorods were assembled by the layer-by-layer technique with the aims of coupling the plasmonic photothermal properties of the metal nanoparticles for plasmonic hyperthermia and the chemoaction of drug DOXO for potential intended combinatorial cancer therapeutics in the future as well as providing different strategies for the controlled and sustained release of the cargo drug molecules. To do that, DOXO could be successfully loaded onto the hybrid nanoconstructs through electrostatic interactions with high efficiencies of up to ca. 78.3 ± 6.9% for the first formed drug layer and 56 ± 13% for the second one, with a total efficiency for the whole system [(PSS/DOXO/PLL)2/HA-coated NRs] of ca. 65.7 ± 1.4%. Nanohybrid internalization was observed to be enhanced by the outer HA layer, which is able to target the CD44 receptors widely overexpressed in some types of cancers as lung, breast, or ovarian ones. Hence, these nanohybrid systems might be versatile nanoplatforms to simultaneously deliver sufficient heat for therapeutic plasmonic hyperthermia and the anticancer drug. Two controlled mechanisms were proposed to modulate the release of the chemodrug, one by means of the enzymatic degradable character of the PLL layer and another by the modulation of the interactions between the polymeric layers through the exploitation of the optical properties of the hybrid particles under near infrared (NIR) laser irradiation. The combination of this bimodal therapeutic approach exerted a synergistic cytotoxic effect on both HeLa and MDA-MB-231 cancer cells in vitro. Cell death mechanisms were also analyzed, elucidating that plasmonic photothermal therapy induces cell necrosis, whereas DOXO activates the cell apoptotic pathway. Therefore, the present NIR laser-induced targeted cancer thermo/chemotherapy represents a novel targeted anticancer strategy with easy control on demand and suitable therapeutic efficacy.

Doxorubicin-loaded gold nanorods: a multifunctional chemo-photothermal nanoplatform for cancer management

“…This showed that free DOX was more toxic than DOX conjugated to a nanocarrier at the same drug concentration. Similar findings were reported by other studies [ 32 – 33 ]. The high cytotoxic effect of free DOX is due to the higher availability of the drug to the cells after cell uptake.…”

Nanoparticle Activation Methods in Cancer Treatment

“…In the latter, the drug is encapsulated using an emulsion method, and when the shell is ruptured by ultrasound irradiation the drugs are released into the tissue [39,79]. While it was successful, only a low loading capacity of doxorubicin in the bubbles was achieved and so the system was adapted to encapsulate the very potent microtubule stabilizing drug paclitaxel [42,79].…”

“…As such, Villar-Alvarez et al reported a particle coating with PLL and incorporated gold nanorods and the chemotherapeutic DOX. The assembled system could decrease the viability of HeLa cells and MDA-MB-231 cells to around 20% when incubated with 2.5 10 NPs/mL; the same concentration of free DOX killed less than 50% of the cancer cells [42]. Similarly, Yildiz et al described two protease degradable amphiphilic copolymers, poly(lactic-co-glycolic acid)-b-poly-L-lysine (PLGA-PLL) and poly(lactic acid)-b-poly(ethylene glycol) (PLA-PEG), which could react with cathepsins.…”

Utilização de Nanopartículas no Tratamento do Câncer: Aspectos Gerais, Mecanismos de Ação Antineoplásicos e Aplicabilidades Tumorais

“…Esses ligantes podem ser anticorpos monoclonais, aptâmeros ou peptídeos 10 . Após a NP ser absorvida pela célula, por meio da formação de micropinossoma e endossomo 12 , o endossoma é fundido com o lisossomo, que ficará responsável por degradar a partícula absorvida 13 . Muitos fármacos utilizam da via endossomal para chegarem ao citosol e iniciarem seus mecanismos de ação 14 .…”