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Gold nanorod-based multifunctional nanocarrier for synergistic chemo-photothermal therapy in tumors.

ABSTRACT: Synergistic photothermal therapy (PTT) and chemotherapy is an efficient strategy for tumor therapy. However, it is still a challenge to design a smart delivery system able to release a drug at the appropriate time and site of action. Here, we have synthesized photosensitive molecule 7-(double dodecylamine)-4-hydroxymethylcoumarin which was introduced in a nanocarrier GNR@SiO₂-DOX@CouC₁₂-HA (GSDCH) to achieve manually controlled drug release. The specific nanocarrier was fabricated using a GNR core for photothermal therapy, a mesoporous silica shell for drug loading, and the coumarin moiety as a blocking agent and intelligent controlled switch. In addition, cellular uptake of GSDCH by HeLa cells can be achieved effectively with the help of hyaluronic acid (HA). Owing to the controlled and targeted drug release properties, the GSDCH with photothermal- and chemo-therapy showed significantly enhanced therapeutic efficiency for HeLa tumor-bearing mice compared to the results of single therapy alone. It indicated that the GSDCH had great potential in tumor therapy with negligible systematic toxicity.

SUBMITTER: Wang Y

PROVIDER: S-EPMC9091941 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Gold nanorod-based multifunctional nanocarrier for synergistic chemo-photothermal therapy in tumors.

Wang Yi Y Cui Qiyao Q Zhao Xiaoshuang X Qin Tang T Wang Wenjing W Sun Hongmei H Zhu Hongda H Guo Huiling H Sun Honghao H

RSC advances 20181211 72

Synergistic photothermal therapy (PTT) and chemotherapy is an efficient strategy for tumor therapy. However, it is still a challenge to design a smart delivery system able to release a drug at the appropriate time and site of action. Here, we have synthesized photosensitive molecule 7-(double dodecylamine)-4-hydroxymethylcoumarin which was introduced in a nanocarrier GNR@SiO<sub>2</sub>-DOX@CouC<sub>12</sub>-HA (GSDCH) to achieve manually controlled drug release. The specific nanocarrier was fab ...[more]

PMID: 35559316

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Project description:Metal nanoparticles (NPs), particularly gold nanorods (AuNRs), appear as excellent platforms not only to transport and deliver bioactive cargoes but also to provide additional therapeutic responses for diseased cells and tissues and/or to complement the action of the carried molecules. In this manner, here, we optimized a previous developed metal-based nanoplatform composed of an AuNR core surrounded by a polymeric shell constructed by means of the layer-by-layer approach, and in which very large amounts of the antineoplasic drug doxorubicin (DOXO) in a single loading step and targeting capability thanks to an outer hyaluronic acid layer were incorporated by means of an optimized fabrication process (PSS/DOXO/PLL/HA-coated AuNRs). The platform retained its nanometer size with a negative surface charge and was colloidally stable in a range of physiological conditions, in which only in some of them some particle clustering was noted with no precipitation. In addition, the dual stimuli-responsiveness of the designed nanoplatform to both endogenous proteases and external applied light stimuli allows to perfectly manipulate the chemodrug release rates and profiles to achieve suitable pharmacodynamics. It was observed that the inherent active targeting abilities of the nanoplatfom allow the achievement of specific cell toxicity in tumoral cervical HeLa cells, whilst healthy ones such as 3T3-Balb fibroblast remain safe and alive in agreement with the detected levels of internalization in each cell line. In addition, the bimodal action of simultaneous chemo- and photothermal bioactivity provided by the platform largely enhances the therapeutic outcomes. Finally, it was observed that our PSS/DOXO/PLL/HA-coated AuNRs induced cell mortality mainly through apoptosis in HeLa cells even in the presence of NIR light irradiation, which agrees with the idea of the chemo-activity of DOXO predominating over the photothermal effect to induce cell death, favoring an apoptotic pathway over necrosis for cell death.

Project description:Chemo-mild photothermal synergistic therapy can effectively inhibit tumor growth under mild hyperthermia, minimizing damage to nearby healthy tissues and skin while ensuring therapeutic efficacy. In this paper, we develop a multifunctional study based on polyhedral oligomeric sesquisiloxane (POSS) that exhibits a synergistic therapeutic effect through mild photothermal and chemotherapy treatments (POSS-SQ-DOX). The nanoplatform utilizes SQ-N as a photothermal agent (PTA) for mild photothermal, while doxorubicin (DOX) serves as the chemotherapeutic drug for chemotherapy. By incorporating POSS into the nanoplatform, we successfully prevent the aggregation of SQ-N in aqueous solutions, thus maintaining its excellent photothermal properties both in vitro and in vivo. Furthermore, the introduction of polyethylene glycol (PEG) significantly enhances cell permeability, which contributes to the remarkable therapeutic effect of POSS-SQ-DOX NPs. Our studies on the photothermal properties of POSS-SQ-DOX NPs demonstrate their high photothermal conversion efficiency (62.3%) and stability, confirming their suitability for use in mild photothermal therapy. A combination index value (CI = 0.72) verified the presence of a synergistic effect between these two treatments, indicating that POSS-SQ-DOX NPs exhibited significantly higher cell mortality (74.7%) and tumor inhibition rate (72.7%) compared to single chemotherapy and mild photothermal therapy. This observation highlights the synergistic therapeutic potential of POSS-SQ-DOX NPs. Furthermore, in vitro and in vivo toxicity tests suggest that the absence of cytotoxicity and excellent biocompatibility of POSS-SQ-DOX NPs provide a guarantee for clinical applications. Therefore, utilizing near-infrared light-triggering POSS-SQ-DOX NPs can serve as chemo-mild photothermal PTA, while functionalized POSS-SQ-DOX NPs hold great promise as a novel nanoplatform that may drive significant advancements in the field of chemo-mild photothermal therapy.

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Gold nanorod-based multifunctional nanocarrier for synergistic chemo-photothermal therapy in tumors.

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Gold nanorod-based multifunctional nanocarrier for synergistic chemo-photothermal therapy in tumors.

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