Encapsulation of Photothermal Nanoparticles in Stealth and pH-Responsive Micelles for Eradication of Infectious Biofilms In Vitro and In Vivo

Photothermal nanoparticles can be used for non-antibiotic-based eradication of infectious biofilms, but this may cause collateral damage to tissue surrounding an infection site. In order to prevent collateral tissue damage, we encapsulated photothermal polydopamine-nanoparticles (PDA-NPs) in mixed shell polymeric micelles, composed of stealth polyethylene glycol (PEG) and pH-sensitive poly(β-amino ester) (PAE). To achieve encapsulation, PDA-NPs were made hydrophobic by electrostatic binding of indocyanine green (ICG). Coupling of ICG enhanced the photothermal conversion efficacy of PDA-NPs from 33% to 47%. Photothermal conversion was not affected by micellar encapsulation. No cytotoxicity or hemolytic effects of PEG-PAE encapsulated PDA-ICG-NPs were observed. PEG-PAE encapsulated PDA-ICG-NPs showed good penetration and accumulation in a Staphylococcus aureus biofilm. Penetration and accumulation were absent when nanoparticles were encapsulated in PEG-micelles without a pH-responsive moiety. PDA-ICG-NPs encapsulated in PEG-PAE-micelles found their way through the blood circulation to a sub-cutaneous infection site after tail-vein injection in mice, yielding faster eradication of infections upon near-infrared (NIR) irradiation than could be achieved after encapsulation in PEG-micelles. Moreover, staphylococcal counts in surrounding tissue were reduced facilitating faster wound healing. Thus, the combined effect of targeting and localized NIR irradiation prevented collateral tissue damage while eradicating an infectious biofilm.

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Real-time monitoring of a controlled drug delivery system in vivo: construction of a near infrared fluorescence monomer conjugated with pH-responsive polymeric micelles

Journal of Materials Chemistry B ◽

10.1039/c6tb00315j ◽

2016 ◽

Vol 4 (19) ◽

pp. 3377-3386 ◽

Cited By ~ 11

Author(s):

Li Chen ◽

Bizheng Chen ◽

Xiaodong Liu ◽

Yujie Xu ◽

Lifen Zhang ◽

...

Keyword(s):

Real Time ◽

Near Infrared ◽

Polymeric Micelles ◽

Controlled Drug Delivery ◽

Polymeric Micelle ◽

Amphiphilic Copolymer ◽

Tumor Site ◽

Ph Responsive ◽

Controlled Drug Delivery System

A self-assembled polymeric micelle from multifunctional amphiphilic copolymer with NIR and pH-sensitive groups can be used to monitor the dynamic process of its arriving at the tumor site in real time.

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Self-Assembly Iron Oxide Nanoclusters for Photothermal-Mediated Synergistic Chemo/Chemodynamic Therapy

Journal of Immunology Research ◽

10.1155/2021/9958239 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Xiang Li ◽

Zhen Wang ◽

Mian Ma ◽

Zhouqing Chen ◽

Xiang-long Tang ◽

...

Keyword(s):

Iron Oxide ◽

Self Assembly ◽

Near Infrared ◽

Light Irradiation ◽

Infrared Light ◽

Photothermal Effect ◽

Photothermal Conversion ◽

Assembly Method

Background and Purpose. Although chemodynamic therapy (CDT) is promising for cancer treatment, its clinical application is still limited because of unresolved issues. In this study, an efficient CDT agent for synergistic chemo/CDT therapy mediated by the photothermal effect was developed by an iron oxide self-assembly method. Methods. Superparamagnetic iron oxide nanoclusters (SPIOCs) were located within the core, which resulted in high photothermal conversion and outstanding generation of reactive oxygen species (ROS). The shell consisted of a human serum albumin- (HSA-) paclitaxel (PTX) layer, which extended the blood circulation time and ensured the effectiveness of the chemotherapy. Arg-Gly-Asp peptides (RGD) were linked to the naked cysteine moieties in HSA to promote the specific targeting of human glioma U87 cells by αvβ3 integrins. Continuous near-infrared light irradiation triggered and promoted the synergistic chemo/CDT therapy through the photothermal effect. Results. Our SPIOCs@HSA-RGD nanoplatform showed well biocompatibility and could target glioma specifically. Photothermal conversion and ROS burst were detected after continuous 808 nm light irradiation, and a significant antitumor effect was achieved. Conclusion. Experimental in vitro and in vivo evaluations showed that our photothermal-mediated chemo/CDT therapy could efficiently inhibit tumor growth and is therefore promising for cancer therapy.

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In-vitro and in-vivo evaluation of pH-responsive polymeric micelles in a photodynamic cancer therapy model

Journal of Pharmacy and Pharmacology ◽

10.1211/0022357011775352 ◽

2001 ◽

Vol 53 (2) ◽

pp. 155-166 ◽

Cited By ~ 42

Author(s):

J. Taillefer ◽

N. Brasseur ◽

J. E. van Lier ◽

V. Lenaerts ◽

D. Le Garrec ◽

...

Keyword(s):

Cancer Therapy ◽

Polymeric Micelles ◽

Ph Responsive ◽

In Vivo Evaluation ◽

Photodynamic Cancer Therapy ◽

Therapy Model

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Erythrocyte Membrane-Enveloped Molybdenum Disulfide Nanodots for Biofilm Elimination on Implants Via Toxin Neutralization and Immune Modulation

10.21203/rs.3.rs-1124131/v1 ◽

2021 ◽

Author(s):

Tingwang Shi ◽

Zesong Ruan ◽

Jianrong Wu ◽

Weijuan Zou ◽

Xiaojun Cai ◽

...

Keyword(s):

Molybdenum Disulfide ◽

Erythrocyte Membrane ◽

Tissue Damage ◽

Immune Modulation ◽

Near Infrared ◽

Erythrocyte Membranes ◽

Clinical Issue ◽

Immunosuppressive Microenvironment

Abstract Backgrounds: Implant-related infections (IRIs) caused by bacterial biofilms remain a prevalent but tricky clinical issue, which are characterized by drug resistance, toxin impairment and immunity suppression. Recently, antimicrobial therapies based on reactive oxygen species (ROS) or hyperthermia have been developed to effectively destroy biofilms. However, all of them have failed to simultaneously focus on the immunosuppressive microenvironment of biofilms and tissue damage caused by bacterial toxins. Results Herein, we proposed a one-arrow-three-hawks strategy to orchestrate hyperthermia/ROS antibiofilm therapy, toxin neutralization and immunomodulatory therapies through engineering a bioinspired erythrocyte membrane-enveloped molybdenum disulfide nanodots (EM@MoS2) nanoplatform. In biofilm microenvironment, pore-forming toxins actively attack the erythrocyte membranes on the nanodots and be detained, thus keeping toxins away from their targets and mitigating tissue damage. Under near-infrared laser irradiation, MoS2 nanodots, with superb photothermal and peroxidase-like properties, exert a powerful synergistic antibiofilm effect. More intriguingly, we initially identified that they possess the ability to reverse the immunosuppressive microenvironment through skewing the macrophages from an anti-inflammatory phenotype to a proinflammatory phenotype, which would promote the elimination of biofilm debris and prevention of infection relapse. Systematic in vitro and in vivo evaluations have demonstrated that EM@MoS2 achieves remarkable antibiofilm effect. Conclusion The current study integrated the functions of hyperthermia/ROS therapy, virulence clearance and immune regulation, which could provide an effective paradigm for IRIs therapy.

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Novel phthalocyanine-based polymeric micelles with high near-infrared photothermal conversion efficiency under 808 nm laser irradiation for in vivo cancer therapy

Journal of Materials Chemistry B ◽

10.1039/c9tb00011a ◽

2019 ◽

Vol 7 (14) ◽

pp. 2247-2251 ◽

Cited By ~ 9

Author(s):

Lu Li ◽

Qingzhu Yang ◽

Lei Shi ◽

Nannan Zheng ◽

Zeyu Li ◽

...

Keyword(s):

Cancer Therapy ◽

Cancer Cells ◽

Laser Irradiation ◽

Conversion Efficiency ◽

Photothermal Therapy ◽

Near Infrared ◽

Polymeric Micelles ◽

Photothermal Conversion ◽

Phthalocyanine Molecule

Novel phthalocyanine molecule 4OCSPC with deep NIR absorbance showed excellent photothermal therapy property for cancer cells.

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A Semimetal-Like Molybdenum Carbide Quantum Dots Photoacoustic Imaging and Photothermal Agent with High Photothermal Conversion Efficiency

Materials ◽

10.3390/ma11091776 ◽

2018 ◽

Vol 11 (9) ◽

pp. 1776 ◽

Cited By ~ 8

Author(s):

Wenhao Dai ◽

Haifeng Dong ◽

Xueji Zhang

Keyword(s):

Quantum Dots ◽

Conversion Efficiency ◽

Molybdenum Carbide ◽

Near Infrared ◽

Photoacoustic Imaging ◽

Therapeutic Interventions ◽

High Concentration ◽

Photothermal Conversion

Theranostic platforms integrating imaging diagnostic and therapeutic interventions into a single nanoplatform have attracted considerable attention for cancer-individualized therapies. However, their uncertain stability, complex pharmacokinetics, and intrinsic toxicology of multiple components hinder their practical application in clinical research. In this paper, stable and high-concentration molybdenum carbide quantum dots (Mo2C QDs) with a diameter of approximately 6 nm and a topographic height of about 1.5 nm were synthesized using a facile sonication-assisted liquid-phase exfoliation approach. The prepared Mo2C QDs exhibited a strong near-infrared (NIR) absorbance with a high molar extinction coefficient of 4.424 Lg−1cm−1 at 808 nm, a high photothermal conversion efficiency of 42.9%, and showed excellent performance on photoacoustic imaging. The Mo2C QDs had high stability and highly biocompatibility, with low cytotoxicity. Under NIR irradiation, a remarkable in vitro and in vivo therapeutic effect was obtained. Such a stable and biocompatible all-in-one theranostic nanoagent generated by facile synthesis that combines promising imaging guidance and effective tumor ablation properties may hold great potential for theranostic nanomedicine.

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Microfluidic-Assisted Preparation of Targeted pH-Responsive Polymeric Micelles Improves Gemcitabine Effectiveness in PDAC: In Vitro Insights

Cancers ◽

10.3390/cancers14010005 ◽

2021 ◽

Vol 14 (1) ◽

pp. 5

Author(s):

Rosa Iacobazzi ◽

Ilaria Arduino ◽

Roberta Di Fonte ◽

Angela Lopedota ◽

Simona Serratì ◽

...

Keyword(s):

Drug Resistance ◽

Colloidal Stability ◽

Polymeric Micelles ◽

3D Models ◽

Physiological Model ◽

Ductal Adenocarcinoma ◽

Ph Responsive ◽

Drug Receptor

Pancreatic ductal adenocarcinoma (PDAC) represents a great challenge to the successful delivery of the anticancer drugs. The intrinsic characteristics of the PDAC microenvironment and drugs resistance make it suitable for therapeutic approaches with stimulus-responsive drug delivery systems (DDSs), such as pH, within the tumor microenvironment (TME). Moreover, the high expression of uPAR in PDAC can be exploited for a drug receptor-mediated active targeting strategy. Here, a pH-responsive and uPAR-targeted Gemcitabine (Gem) DDS, consisting of polymeric micelles (Gem@TpHResMic), was formulated by microfluidic technique to obtain a preparation characterized by a narrow size distribution, good colloidal stability, and high drug-encapsulation efficiency (EE%). The Gem@TpHResMic was able to perform a controlled Gem release in an acidic environment and to selectively target uPAR-expressing tumor cells. The Gem@TpHResMic displayed relevant cellular internalization and greater antitumor properties than free Gem in 2D and 3D models of pancreatic cancer, by generating massive damage to DNA, in terms of H2AX phosphorylation and apoptosis induction. Further investigation into the physiological model of PDAC, obtained by a co-culture of tumor spheroids and cancer-associated fibroblast (CAF), highlighted that the micellar system enhanced the antitumor potential of Gem, and was demonstrated to overcome the TME-dependent drug resistance. In vivo investigation is warranted to consider this new DDS as a new approach to overcome drug resistance in PDAC.

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Comparison of Gold Nanospheres, Nanorods, Nanocages and Nanoflowers for Combined Photothermal-Radiotherapy of Cancer

NANO ◽

10.1142/s1793292021500375 ◽

2021 ◽

pp. 2150037

Author(s):

Lijie Yang ◽

Jinhua Wang ◽

Liying Sun ◽

Yisi Zhang ◽

Peng Huang ◽

...

Keyword(s):

Gold Nanoparticles ◽

Conversion Efficiency ◽

Near Infrared ◽

Enhancement Effect ◽

Gold Nanospheres ◽

Photothermal Conversion ◽

Uptake Efficiency ◽

Gold Nanoflowers

Gold nanoparticles are promising dual agents for combined photothermal-radiotherapy of cancer. Nevertheless, the shape effects of gold nanoparticles on photothermal conversion efficiency and radiosensitization have not been completely revealed. To address this knowledge gap, different shapes of gold nanoparticles including gold nanospheres (GNSs), gold nanorods (GNRs), gold nanocages (GNCs) and gold nanoflowers (GNFs) were synthesized. Despite being subjected to the same modification with poly (ethylene glycol) (PEG), these gold nanoparticles showed different cellular uptake efficiencies: GNFs[Formula: see text][Formula: see text][Formula: see text]GNSs[Formula: see text][Formula: see text][Formula: see text]GNCs[Formula: see text][Formula: see text][Formula: see text]GNRs. Moreover, GNRs, GNCs and GNFs could convert near-infrared (NIR) light to heat and GNFs displayed the highest photothermal conversion efficiency, whereas GNSs showed poor photothermal effects due to the weak NIR absorption. The highest uptake efficiency as well as the best photothermal conversion ability led to GNFs to exhibit the best photothermal therapeutic effect. Furthermore, all the gold nanoparticles could be used as radiosensitizers to improve radiotherapeutic effect. Among these nanoparticles, GNFs showed the best radiation enhancement effect because of their highest uptake efficiency. Furthermore, a higher accumulation of GNFs in tumor tissues was observed than those of other shaped gold nanoparticles. Importantly, our in vitro and in vivo comparative studies revealed that GNFs possessed the strongest anticancer effect in combined photothermal-radiotherapy. Hence, compared to gold nanoparticles with other shapes, the GNFs might be more desirable dual agents for highly efficient combined photothermal-radiotherapy.

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