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PPy nanoneedle based nanoplatform capable of overcoming biological barriers for synergistic chemo-photothermal therapy.

ABSTRACT: The biological barriers in vivo have limited the site-specific bioavailability and impeded therapeutic efficacy. To tackle these issues, nonspherical particles with a shape effect have attracted wide attention to affect the in vivo translocation of a drug delivery system. Herein, we constructed a nanoplatform based on polypyrrole (PPy) nanoneedles by hyaluronic acid (HA) modification and doxorubicin (DOX) loading. The PPy-HA@DOX nanoneedles with high aspect ratios could enhance the extravasation through the fenestrated vasculature of tumors, transport across tumor cell membrane via an endocytosis mechanism or even penetrated the membrane directly, and ultimately enter the nucleus easily via the nuclear pore complex by passive diffusion. With the ability of overcoming biological barriers, the PPy nanoneedle based nanoplatform would deliver drugs into the organelles more effectively. Under near infrared (NIR) laser irradiation, PPy as the photothermal agent could lead to tumor cellular structure damage for photothermal therapy (PTT). Therefore, PPy-HA@DOX developed here would exploit the merits of synergistic combination of chemo-photothermal therapy, which would pave the way toward more effective nanotherapeutics.

SUBMITTER: Yin Y

PROVIDER: S-EPMC9049910 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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PPy nanoneedle based nanoplatform capable of overcoming biological barriers for synergistic chemo-photothermal therapy.

Yin Yanyan Y Hao Yutong Y Wang Ning N Yang Pengfei P Li Na N Zhang Xiaoyi X Song Yu Y Feng Xuebing X Ma Weiwei W

RSC advances 20200224 13

The biological barriers <i>in vivo</i> have limited the site-specific bioavailability and impeded therapeutic efficacy. To tackle these issues, nonspherical particles with a shape effect have attracted wide attention to affect the <i>in vivo</i> translocation of a drug delivery system. Herein, we constructed a nanoplatform based on polypyrrole (PPy) nanoneedles by hyaluronic acid (HA) modification and doxorubicin (DOX) loading. The PPy-HA@DOX nanoneedles with high aspect ratios could enhance the ...[more]

PMID: 35492174

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Project description:Background and Purpose:The development of multiple drug resistance (MDR) to chemotherapy and single modal therapy remains unsatisfied for the eradication of tumor, which are major obstacles in cancer therapy. This novel system with excellent characteristics for inhibition of P-glycoprotein (P-gp), and for near-infrared fluorescence (NIRF) imaging-guided chemo-photothermal therapy (PTT), has been identified as a promising way to MDR and achieve synergistic cancer therapy. Methods:In this study, we successfully synthesized a multifunctional theranostic system, which was developed through FDA-approved self-assembling drugs, which contain anticancer drug doxorubicin (Dox), imaging and high photothermal conversion drug indocyanine green (ICG) and P-gp regulator TPGS (the system named T/Dox-ICG). We studied the characterization of T/Dox-ICG NPs, including the TEM, SEM, DLS, UV-vis-NIR, zeta potential, CLSM, in vitro FL imaging, in vitro photothermal effect, in vitro Dox and ICG release. We used CLSM to verify the location of intracellular distribution of Dox in SCG 7901/VCR cells, Western blot was performed to demonstrate the TPGS-mediated inhibition of P-gp. And, the cytotoxicity of materials against SCG 7901/VCR cells was studied by the MTT assay. Results:The TEM showed the T/Dox-ICG NPs had good monodispersity with diameters of 19.03 nm, Dox and ICG could be released constantly from T/Dox-ICG NPs in vitro. In vitro cell experiments demonstrated higher Dox accumulation and retention in the nucleus. Western blot showed TPGS could obviously inhibit the expression of P-gp. In vitro cytotoxicity assay showed more significant cytotoxicity on MDR cells (SCG 7901/VCR) with only 8.75% of cells surviving. Conclusion:MDR cancer therapy indicates that it may be important to develop a safer system that can simultaneously inhibit the drug transporters and monitor the delivery of chemotherapeutic agents, and combination therapy have raised widespread concern on tumor treatment.

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.

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PPy nanoneedle based nanoplatform capable of overcoming biological barriers for synergistic chemo-photothermal therapy.

Publications

PPy nanoneedle based nanoplatform capable of overcoming biological barriers for synergistic chemo-photothermal therapy.

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