Liangran Guo

Combinatorial Photothermal and Immuno Cancer Therapy Using Chitosan-Coated Hollow Copper Sulfide Nanoparticles

Near-infrared light-responsive inorganic nanoparticles have been shown to enhance the efficacy of cancer photothermal ablation therapy. However, current nanoparticle-mediated photothermal ablation is more effective in treating local cancer at the primary site than metastatic cancer. Here, we report the design of a near-infrared light-induced transformative nanoparticle platform that combines photothermal ablation with immunotherapy. The design is based on chitosan-coated hollow CuS nanoparticles that assemble the immunoadjuvants oligodeoxynucleotides containing the cytosine-guanine (CpG) motifs. Interestingly, these structures break down after laser excitation, reassemble, and transform into polymer complexes that improve tumor retention of the immunotherapy. In this “photothermal immunotherapy” approach, photothermal ablation-induced tumor cell death reduces tumor growth and releases tumor antigens into the surrounding milieu, while the immunoadjuvants potentiate host antitumor immunity. Our results indicated that combined photothermal immunotherapy is more effective than either immunotherapy or photothermal therapy alone against primary treated and distant untreated tumors in a mouse breast cancer model. These hollow CuS nanoparticles are biodegradable and can be eliminated from the body after laser excitation.

A Comparative Study of Hollow Copper Sulfide Nanoparticles and Hollow Gold Nanospheres on Degradability and Toxicity

Gold and copper nanoparticles have been widely investigated for photothermal therapy of cancer. However, degradability and toxicity of these nanoparticles remain concerns. Here, we compare hollow CuS nanoparticles (HCuSNPs) with hollow gold nanospheres (HAuNS) in similar particle sizes and morphology following intravenous administration to mice. The injected pegylated HCuSNPs (PEG-HCuSNPs) are eliminated through both hepatobiliary (67 percentage of injected dose, %ID) and renal (23 %ID) excretion within one month postinjection. By contrast, 3.98 %ID of Au is excreted from liver and kidney within one month after iv injection of pegylated HAuNS (PEG-HAuNS). Comparatively, PEG-HAuNS are almost nonmetabolizable, while PEG-HCuSNPs are considered biodegradable nanoparticles. PEG-HCuSNPs do not show significant toxicity by histological or blood chemistry analysis. Principal component analysis and 2-D peak distribution plots of data from matrix-assisted laser desorption ionization-time-of-flight imaging mass spectrometry (MALDI-TOF IMS) of liver tissues demonstrated a reversible change in the proteomic profile in mice receiving PEG-HCuSNPs. This is attributed to slow dissociation of Cu ion from CuS nanoparticles along with effective Cu elimination for maintaining homeostasis. Nonetheless, an irreversible change in the proteomic profile is observed in the liver from mice receiving PEG-HAuNS by analysis of MALDI-TOF IMS data, probably due to the nonmetabolizability of Au. This finding correlates with the elevated serum lactate dehydrogenase at 3 months after PEG-HAuNS injection, indicating potential long-term toxicity. The comparative results between the two types of nanoparticles will advance the development of HCuSNPs as a new class of biodegradable inorganic nanomaterials for photothermal therapy.

Hollow Copper Sulfide Nanoparticle-Mediated Transdermal Drug Delivery

A photothermal ablation-enhanced transdermal drug delivery methodology is developed based on hollow copper sulfide nanoparticles (HCuSNPs) with intense photothermal coupling effects. Application of nanosecond-pulsed near-infrared laser allows rapid heating of the nanoparticles and instantaneous heat conduction. This provides very short periods of time but extremely high temperatures in local regions, with focused thermal ablation of the stratum corneum. The depth of skin perforations can be controlled by adjusting the laser power. Skin disruption by HCuSNP-mediated photothermal ablation significantly increases the permeability of human growth hormone. This technique offers compelling opportunities for macromolecular drug and vaccine delivery.

Regulation of carboxylesterase‐2 expression by p53 family proteins and enhanced anti‐cancer activities among 5‐fluorouracil, irinotecan and doxazolidine prodrug

For four decades, 5‐fluorouracil (5‐FU) has been a major anti‐cancer medicine. This drug is increasingly used with other anti‐cancer agents such as irinotecan. Irinotecan and many others such as PPD (pentyl carbamate of p‐aminobenzyl carbamate of doxazolidine) require activation by carboxylesterase‐2 (CES2). 5‐FU, on the other hand, reportedly induces CES2 in colorectal tumour lines. The aims of this study were to determine the molecular basis for the induction and to ascertain interactive cell‐killing activity between 5‐FU and ester prodrugs.

Deficiency in Nrf2 Transcription Factor Decreases Adipose Tissue Mass and Hepatic Lipid Accumulation in Leptin Deficient Mice

To evaluate whether Nrf2 deficiency impacts insulin resistance and lipid accumulation in liver and white adipose tissue.

Laser ablation-enhanced transdermal drug delivery

Abstract: Transdermal delivery offers an excellent route for drug and vaccine administration. Nonetheless, the lipid-rich outer stratum corneum layer of the skin presents a critical challenge to drug penetration. Laser ablation perforates epidermis through selective photothermolysis, making skin more permeable to hydrophilic and macromolecular drugs such as peptides, proteins, and genes. This review summarizes recent applications to laser ablation-enhanced transdermal delivery. Needle- and pain-free transcutaneous drug delivery via laser ablation provides an alternative approach to achieve local or systemic therapeutics. Zusammenfassung: Die transdermale Applikation bietet eine hervorragende Möglichkeit für die Verabreichung von Medikamenten und Impfstoffen, stellt aber aufgrund der lipidreichen äußeren Hornschicht der Haut eine besondere Herausforderung dar. Mittels Laserablation kann die Epidermis durch selektive Photothermolyse perforiert werden, was die Haut durchlässig für hydrophile und makromolekulare Substanzen wie Peptide, Proteine und Gene macht. Der vorliegende Review-Artikel fasst die neuesten Anwendungen der Laserablations-verstärkten Verabreichung von Wirkstoffen zusammen. Die nadel- und schmerzfreie transkutane Prozedur mittels Laserablation bietet einen alternativen Ansatz zur Verabreichung lokaler oder systemischer Therapeutika.

Enhanced reactive oxygen species through direct copper sulfide nanoparticle-doxorubicin complexation

CuS-based nanostructures loading the chemotherapeutic agent doxorubicin (DOX) exerted excellent cancer photothermal chemotherapy under multi-external stimuli. The DOX loading was generally designed through electrostatic interaction or chemical linkers. However, the interaction between DOX molecules and CuS nanoparticles has not been investigated. In this work, we use PEGylated hollow copper sulfide nanoparticles (HCuSNPs) to directly load DOX through the DOX/Cu2+ chelation process. Distinctively, the synthesized PEG-HCuSNPs-DOX release the DOX/Cu2+ complexes into surrounding environment, which generate significant reactive oxygen species (ROS) in a controlled manner by near-infrared laser. The CuS nanoparticle-mediated photothermal ablation facilitates the ROS-induced cancer cell killing effect. Our current work reveals a DOX/Cu2+-mediated ROS-enhanced cell-killing effect in addition to conventional photothermal chemotherapy through the direct CuS nanoparticle-DOX complexation.

Photothermal Properties of Hollow Gold Nanostructures for Cancer Theranostics

Cancer theranostic agents are defined as integrated platforms, which can combine the tumor diagnosis, therapeutic, or even therapeutic evaluation functions in one system. Hollow gold (Au) nanostructures have been emerging as promising nanoplatforms for cancer theranostics because of their specific structure and unique optical property for both cancer imaging and therapeutics. Au nanocages, hollow Au nanospheres, and hollow Au nanoshells are three kinds of hollow Au nanostructures widely investigated in the recent years. This chapter briefly summarizes the synthesis methods and cancer theranostic applications of the above three kinds of Au nanostructures, aiming to highlight the importance and potential future use of these agents.