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1.
Biomater Sci ; 12(10): 2705-2716, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38607326

ABSTRACT

Developing effective nanomedicines to cross the blood-brain barrier (BBB) for efficient glioma theranostics is still considered to be a challenging task. Here, we describe the development of macrophage membrane (MM)-coated nanoclusters (NCs) of ultrasmall iron oxide nanoparticles (USIO NPs) with dual pH- and reactive oxygen species (ROS)-responsivenesses for magnetic resonance (MR) imaging and chemotherapy/chemodynamic therapy (CDT) of orthotopic glioma. Surface citrate-stabilized USIO NPs were solvothermally synthesized, sequentially modified with ethylenediamine and phenylboronic acid, and cross-linked with gossypol to form gossypol-USIO NCs (G-USIO NCs), which were further coated with MMs. The prepared MM-coated G-USIO NCs (G-USIO@MM NCs) with a mean size of 99.9 nm display tumor microenvironment (TME)-responsive gossypol and Fe release to promote intracellular ROS production and glutathione consumption. With the MM-mediated BBB crossing and glioma targeting, the G-USIO@MM NCs can specifically inhibit orthotopic glioma in vivo through the gossypol-mediated chemotherapy and Fe-mediated CDT. Meanwhile, USIO NPs can be dissociated from the NCs under the TME, thus allowing for effective T1-weighted glioma MR imaging. The developed G-USIO@MM NCs with simple components and drug as a crosslinker are promising for glioma theranostics, and may be extended to tackle other cancer types.


Subject(s)
Glioma , Macrophages , Theranostic Nanomedicine , Glioma/diagnostic imaging , Glioma/drug therapy , Glioma/metabolism , Glioma/pathology , Animals , Mice , Macrophages/metabolism , Macrophages/drug effects , Magnetic Iron Oxide Nanoparticles/chemistry , Magnetic Resonance Imaging , Humans , Cell Line, Tumor , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Reactive Oxygen Species/metabolism , Cell Membrane/metabolism , Tumor Microenvironment/drug effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects
2.
Adv Healthc Mater ; : e2400114, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38581263

ABSTRACT

The development of functional nanoplatforms to improve the chemotherapy outcome and inhibit distal cancer cell metastasis remains an extreme challenge in cancer management. In this work, a human-derived PC-3 cancer cell membrane-camouflaged chitosan-polypyrrole nanogel (CH-PPy NG) platform, which can be loaded with chemotherapeutic drug docetaxel (DTX) and RANK siRNA for targeted chemotherapy and gene silencing-mediated metastasis inhibition of late-stage prostate cancer in a mouse model, is reported. The prepared NGs with a size of 155.8 nm show good biocompatibility, pH-responsive drug release profile, and homologous targeting specificity to cancer cells, allowing for efficient and precise drug/gene co-delivery. Through in-vivo antitumor treatment in a xenografted PC-3 mouse tumor model, it is shown that such a CH-PPy NG-facilitated co-delivery system allows for effective chemotherapy to slow down the tumor growth rate, and effectively inhibits the metastasis of prostate cancer to the bone via downregulation of the RANK/RANKL signaling pathway. The created CH-Ppy NGs may be utilized as a promising platform for enhanced chemotherapy and anti-metastasis treatment of prostate cancer.

3.
Int J Biol Macromol ; 258(Pt 1): 128874, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38128797

ABSTRACT

This study presents a novel approach in the synthesis and characterization of nanocomposites comprising cationic chitosan (CCS) blended with varying concentrations of silver nanoparticles/montmorillonite (AgNPs/MMT). AgNPs/MMT was synthesized using soluble starch as a reducing and stabilizing agent. Subsequently, nanocomposites, namely CCS/AgMMT-0, CCS/AgMMT-0.5, CCS/AgMMT-1.5, and CCS/AgMMT-2.5, were developed by blending 2.5 g of CCS with 0, 0.5, 1.5, and 2.5 g of AgNPs/MMT, respectively, and the corresponding nanocomposites were prepared using ball milling technique. Transmission electron microscopy (TEM) analysis revealed the formation of nanocomposites that exhibiting nearly spherical morphologies. Dynamic light scattering (DLS) measurements displayed average particle sizes of 1183 nm, 131 nm, 140 nm, and 188 nm for CCS/AgMMT-0, CCS/AgMMT-0.5, CCS/AgMMT-1.5, and CCS/AgMMT-2.5, respectively. The narrow polydispersity index (~0.5) indicated uniform particle size distributions across the nanocomposites, affirming monodispersity. Moreover, the zeta potential values exceeding 30 mV across all nanocomposites that confirmed their stability against agglomeration. Notably, CCS/AgMMT-2.5 nanocomposite exhibited potent antibacterial and antibiofilm properties against diverse pipeline materials. Findings showed that after 15 days of incubation, the highest populations of biofilm cells, Pseudomonas aeruginosa biofilm, developed over UPVC, MDPE, DCI, and SS, with corresponding HPCs of 4.79, 6.38, 8.81, and 7.24 CFU/cm2. The highest cell densities of Enterococcus faecalis biofilm in the identical situation were 4.19, 5.89, 8.12, and 6.9 CFU/cm2. The nanocomposite CCS/AgMMT-2.5 exhibited the largest measured zone of inhibition (ZOI) against both P. aeruginosa and E. faecalis, with measured ZOI values of 19 ± 0.65 and 17 ± 0.21 mm, respectively. Remarkably, the research indicates that the youngest biofilm exhibited the most notable rate of inactivation when exposed to a dose of 150 mg/L, in comparison to the mature biofilm. These such informative findings could offer valuable insights into the development of effective antibiofilm agents and materials applicable in diverse sectors such as water treatment facilities, medical devices, and industrial pipelines.


Subject(s)
Chitosan , Metal Nanoparticles , Nanocomposites , Silver/pharmacology , Bentonite/pharmacology , Chitosan/pharmacology , Anti-Bacterial Agents/pharmacology , Cations/pharmacology , Biofilms , Microbial Sensitivity Tests
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