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result(s) for
"Lehto, Vesa‐Pekka"
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Cell membrane coating integrity affects the internalization mechanism of biomimetic nanoparticles
2021
Cell membrane coated nanoparticles (NPs) have recently been recognized as attractive nanomedical tools because of their unique properties such as immune escape, long blood circulation time, specific molecular recognition and cell targeting. However, the integrity of the cell membrane coating on NPs, a key metrics related to the quality of these biomimetic-systems and their resulting biomedical function, has remained largely unexplored. Here, we report a fluorescence quenching assay to probe the integrity of cell membrane coating. In contradiction to the common assumption of perfect coating, we uncover that up to 90% of the biomimetic NPs are only partially coated. Using in vitro homologous targeting studies, we demonstrate that partially coated NPs could still be internalized by the target cells. By combining molecular simulations with experimental analysis, we further identify an endocytic entry mechanism for these NPs. We unravel that NPs with a high coating degree (≥50%) enter the cells individually, whereas the NPs with a low coating degree (<50%) need to aggregate together before internalization. This quantitative method and the fundamental understanding of how cell membrane coated NPs enter the cells will enhance the rational designing of biomimetic nanosystems and pave the way for more effective cancer nanomedicine.
Cell membrane coating of nanomaterials has become an attractive method of improving targeting, residence and biocompatibility. Here, the authors demonstrated that most nanoparticles are only partially coated by standard methods, and show the coating degree can impact the biological fate of nanoparticles.
Journal Article
Systematic design of cell membrane coating to improve tumor targeting of nanoparticles
2022
Cell membrane (CM) coating technology is increasingly being applied in nanomedicine, but the entire coating procedure including adsorption, rupture, and fusion is not completely understood. Previously, we showed that the majority of biomimetic nanoparticles (NPs) were only partially coated, but the mechanism underlying this partial coating remains unclear, which hinders the further improvement of the coating technique. Here, we show that partial coating is an intermediate state due to the adsorption of CM fragments or CM vesicles, the latter of which could eventually be ruptured under external force. Such partial coating is difficult to self-repair to achieve full coating due to the limited membrane fluidity. Building on our understanding of the detailed coating process, we develop a general approach for fixing the partial CM coating: external phospholipid is introduced as a helper to increase CM fluidity, promoting the final fusion of lipid patches. The NPs coated with this approach have a high ratio of full coating (~23%) and exhibit enhanced tumor targeting ability in comparison to the NPs coated traditionally (full coating ratio of ~6%). Our results provide a mechanistic basis for fixing partial CM coating towards enhancing tumor accumulation.
Surface modification of nanoparticles by cell membrane (CM) coating to improve their bio-interface properties often results in partial coating. Here the authors show that partial coating is an intermediate state due to the absorption of CM fragments or vesicles and can be resolved by increasing CM fluidity with external phospholipids.
Journal Article
From structural design to delivery: mRNA therapeutics for cancer immunotherapy
by
Tao, Wei
,
Xu, Zhi Ping
,
Lehto, Vesa‐Pekka
in
Adjuvants
,
Anticancer properties
,
Antigen-presenting cells
2024
mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority in expressing all sequence‐known proteins in vivo. In particular, with a small dosage of delivered mRNA, antigen‐presenting cells (APCs) can synthesize mutant neo‐antigens and multi‐antigens and present epitopes to T lymphocytes to elicit antitumor effects. In addition, expressing receptors like chimeric antigen receptor (CAR), T‐cell receptor (TCR), CD134, and immune‐modulating factors including cytokines, interferons, and antibodies in specific cells can enhance immunological response against tumors. With the maturation of in vitro transcription (IVT) technology, large‐scale and pure mRNA encoding specific proteins can be synthesized quickly. However, the clinical translation of mRNA‐based anticancer strategies is restricted by delivering mRNA into target organs or cells and the inadequate endosomal escape efficiency of mRNA. Recently, there have been some advances in mRNA‐based cancer immunotherapy, which can be roughly classified as modifications of the mRNA structure and the development of delivery systems, especially the lipid nanoparticle platforms. In this review, the latest strategies for overcoming the limitations of mRNA‐based cancer immunotherapies and the recent advances in delivering mRNA into specific organs and cells are summarized. Challenges and opportunities for clinical applications of mRNA‐based cancer immunotherapy are also discussed. Systemic or topical mRNA delivery for immune function modulation is emerging as a promising option for cancer immunotherapy. In this review, strategies for enhancing mRNA‐based cancer immunotherapy from the perspective of mRNA structure design and delivery systems are first summarized. Advances of delivering mRNA into specific organs or cells for cancer treatment and opportunities in clinical translation are discussed.
Journal Article
A review on the effectiveness of nanocomposites for the treatment and recovery of oil spill
by
Doshi, Bhairavi
,
Lehto, Vesa-Pekka
,
Sillanpää, Mika
in
aquatic organisms
,
Aquatic Pollution
,
Atmospheric Protection/Air Quality Control/Air Pollution
2023
The introduction of unintended oil spills into the marine ecosystem has a significant impact on aquatic life and raises important environmental concerns. The present review summarizes the recent studies where nanocomposites are applied to treat oil spills. The review deals with the techniques used to fabricate nanocomposites and identify the characteristics of nanocomposites beneficial for efficient recovery and treatment of oil spills. It classifies the nanocomposites into four categories, namely bio-based materials, polymeric materials, inorganic-inorganic nanocomposites, and carbon-based nanocomposites, and provides an insight into understanding the interactions of these nanocomposites with different types of oils. Among nanocomposites, bio-based nanocomposites are the most cost-effective and environmentally friendly. The grafting or modification of magnetic nanoparticles with polymers or other organic materials is preferred to avoid oxidation in wet conditions. The method of synthesizing magnetic nanocomposites and functionalization polymer is essential as it influences saturation magnetization. Notably, the inorganic polymer-based nanocomposite is very less developed and studied for oil spill treatment. Also, the review covers some practical considerations for treating oil spills with nanocomposites. Finally, some aspects of future developments are discussed. The terms “Environmentally friendly,” “cost-effective,” and “low cost” are often used, but most of the studies lack a critical analysis of the cost and environmental damage caused by chemical alteration techniques. However, the oil and gas industry will considerably benefit from the stimulation of ideas and scientific discoveries in this field.
Journal Article
Biogenic nanoporous silicon carrier improves the efficacy of buparvaquone against resistant visceral leishmaniasis
by
Thapa, Rinez
,
Lehto, Vesa-Pekka
,
Näkki, Simo
in
Animals
,
Antiprotozoal Agents - administration & dosage
,
Antiprotozoal Agents - therapeutic use
2021
Visceral leishmaniasis is a vector-borne protozoan infection that is fatal if untreated. There is no vaccination against the disease, and the current chemotherapeutic agents are ineffective due to increased resistance and severe side effects. Buparvaquone is a potential drug against the leishmaniases, but it is highly hydrophobic resulting in poor bioavailability and low therapeutic efficacy. Herein, we loaded the drug into silicon nanoparticles produced from barley husk, which is an agricultural residue and widely available. The buparvaquone-loaded nanoparticles were several times more selective to kill the intracellular parasites being non-toxic to macrophages compared to the pure buparvaquone and other conventionally used anti-leishmanial agents. Furthermore, the in vivo results revealed that the intraperitoneally injected buparvaquone-loaded nanoparticles suppressed the parasite burden close to 100%. By contrast, pure buparvaquone suppressed the burden only by 50% with corresponding doses. As the conclusion, the biogenic silicon nanoparticles are promising carriers to significantly improve the therapeutic efficacy and selectivity of buparvaquone against resistant visceral leishmaniasis opening a new avenue for low-cost treatment against this neglected tropical disease threatening especially the poor people in developing nations.
Journal Article
Triple Contrast CT Method Enables Simultaneous Evaluation of Articular Cartilage Composition and Segmentation
by
Honkanen Miitu K M
,
Saukko Annina E A
,
Lovric Goran
in
Bismuth
,
Cartilage
,
Cartilage (articular)
2020
Early degenerative changes of articular cartilage are detected using contrast-enhanced computed tomography (CT) with a cationic contrast agent (CA). However, cationic CA diffusion into degenerated cartilage decreases with proteoglycan depletion and increases with elevated water content, thus hampering tissue evaluation at early diffusion time points. Furthermore, the contrast at synovial fluid-cartilage interface diminishes as a function of diffusion time hindering accurate cartilage segmentation. For the first time, we employ quantitative dual-energy CT (QDECT) imaging utilizing a mixture of three CAs (cationic CA4+ and non-ionic gadoteridol which are sensitive to proteoglycan and water contents, respectively, and bismuth nanoparticles which highlight the cartilage surface) to simultaneously segment the articulating surfaces and determine of the cartilage condition. Intact healthy, proteoglycan-depleted, and mechanically injured bovine cartilage samples (n = 27) were halved and imaged with synchrotron microCT 2-h post immersion in triple CA or in dual CA (CA4+ and gadoteridol). CA4+ and gadoteridol partitions were determined using QDECT, and pairwise evaluation of these partitions was conducted for samples immersed in dual and triple CAs. In conclusion, the triple CA method is sensitive to proteoglycan depletion while maintaining sufficient contrast at the articular surface to enable detection of cartilage lesions caused by mechanical impact.
Journal Article
Biomimetic Inorganic Nanovectors as Tumor-Targeting Theranostic Platform against Triple-Negative Breast Cancer
by
Wen, Huang
,
Lehto, Vesa-Pekka
,
Batnasan, Enkhzaya
in
Biomimetics
,
Bisphosphonates
,
Breast cancer
2023
Mesoporous silicon nanoparticles (PSi NPs) are promising platforms of nanomedicine because of their good compatibility, high payload capacities of anticancer drugs, and easy chemical modification. Here, PSi surfaces were functionalized with bisphosphonates (BP) for radiolabeling, loaded with doxorubicin (DOX) for chemotherapy, and the NPs were coated with cancer cell membrane (CCm) for homotypic cancer targeting. To enhance the CCm coating, the NP surfaces were covered with polyethylene glycol prior to the CCm coating. The effects of the BP amount and pH conditions on the radiolabeling efficacy were studied. The maximum BP was (2.27 wt%) on the PSi surfaces, and higher radiochemical yields were obtained for 99mTc (97% ± 2%) and 68Ga (94.6% ± 0.2%) under optimized pH conditions (pH = 5). The biomimetic NPs exhibited a good radiochemical and colloidal stability in phosphate-buffered saline and cell medium. In vitro studies demonstrated that the biomimetic NPs exhibited an enhanced cellular uptake and increased delivery of DOX to cancer cells, resulting in better chemotherapy than free DOX or pure NPs. Altogether, these findings indicate the potential of the developed platform for cancer treatment and diagnosis.
Journal Article
Experimental Evaluation of Radiation Response and Thermal Properties of NPs-Loaded Tissues-Mimicking Phantoms
by
Lehto, Vesa-Pekka
,
Asadi, Somayeh
,
Voliani, Valerio
in
Cancer therapies
,
Convection
,
Diffusivity
2022
Many efforts have recently concentrated on constructing and developing nanoparticles (NPs) as promising thermal agent for optical hyperthermia and photothermal therapy. However, thermal energy transfer in biological tissue is a complex process involving different mechanisms such as conduction, convection, radiation. Therefore, having information about thermal properties of tissue especially when NPs are embedded in is a necessity for predicting the heat transfer during hyperthermia. In this work, the thermal properties of solid phantom based on agar in the presence of three different nanoparticles (BPSi, tNAs, GNRs) and alone were measured and reported as a function of temperature (ranging from 22 to 62 °C). The thermal response of these NPs to an 808 nm laser beam with three different powers were studied in the water comparatively. Agar and tNAs have almost constant thermal properties in the considered range. Among the three NPs, gold has the highest conductivity and diffusivity. At 62 °C BPSi NPs have the similar amount of increase for the diffusivity. The thermal parameters reported in this paper can be useful for the mathematical modeling. Irradiation of the NPs-loaded water phantom displayed the highest radiosensitivity of gold among the three mentioned NPs. However, for the higher power of irradiation, BPSi and tNAs NPs showed the increased absorption of heat during shorter time and the increased temperature gradient slope for the initial 15 s after the irradiation started. The three NPs showed different thermal and irradiation response behavior; however, this comparison study notes the worth of having information about thermal parameters of NPs-loaded tissue for pre-clinical planning.
Journal Article
Engineering Carbon Nitride Quantum Dots via Sulfur Doping for Controlled Reactive Oxygen Species Generation
by
Belko, Nikita
,
Filonenko, Elena
,
Brezhneva, Nadzeya
in
Absorption spectroscopy
,
Biocompatibility
,
Carbon
2026
Carbon nitride quantum dots (CNQDs) are emerging as versatile photocatalytic materials with promising applications in biomedicine and environmental remediation. In this study, we synthesized pristine and sulfur‐doped CNQDs via a hydrothermal method, and characterized them using transmission electron microscopy (TEM), X‐ray photoelectron spectroscopy (XPS), and UV–vis absorption spectroscopy. For the first time, the quantum yields of superoxide and singlet oxygen generation were measured for CNQDs. Sulfur doping was found to significantly enhance superoxide generation while concurrently suppressing singlet oxygen production, offering a powerful mechanism for tailoring reactive oxygen species (ROS) output. In addition, all CNQD samples produced hydrogen peroxide and hydroxyl radicals. The ability of these nanomaterials to produce multiple ROS types underscores their potential as hypoxia‐resistant photosensitizers (PSs) for photodynamic therapy (PDT) and as efficient photocatalysts for pollutant degradation. Pristine and sulfur‐doped carbon nitride quantum dots are prepared via hydrothermal “bottom‐up” synthesis. Quantum yields of superoxide and singlet oxygen generation are measured. Sulfur doping is shown to boost photocatalytic production of superoxide by carbon nitride quantum dots while suppressing singlet oxygen generation. The quantum dots also demonstrate efficient photocatalytic hydrogen peroxide and hydroxyl radical production.
Journal Article
Development of Focused Ultrasound-Assisted Nanoplexes for RNA Delivery
by
Lehto, Vesa-Pekka
,
Ranjan, Sanjeev
,
Lukkari, Hannamari
in
Acids
,
Acoustics
,
Addition polymerization
2024
RNA-based therapeutics, including siRNA, have obtained recognition in recent years due to their potential to treat various chronic and rare diseases. However, there are still limitations to lipid-based drug delivery systems in the clinical use of RNA therapeutics due to the need for optimization in the design and the preparation process. In this study, we propose adaptive focused ultrasound (AFU) as a drug loading technique to protect RNA from degradation by encapsulating small RNA in nanoliposomes, which we term nanoplexes. The AFU method is non-invasive and isothermal, as nanoplexes are produced without direct contact with any external materials while maintaining precise temperature control according to the desired settings. The controllability of sample treatments can be effectively modulated, allowing for a wide range of ultrasound intensities to be applied. Importantly, the absence of co-solvents in the process eliminates the need for additional substances, thereby minimizing the potential for cross-contaminations. Since AFU is a non-invasive method, the entire process can be conducted under sterile conditions. A minimal volume (300 μL) is required for this process, and the treatment is speedy (10 min in this study). Our in vitro experiments with silencer CD44 siRNA, which performs as a model therapeutic drug in different mammalian cell lines, showed encouraging results (knockdown > 80%). To quantify gene silencing efficacy, we employed quantitative polymerase chain reaction (qPCR). Additionally, cryo-electron microscopy (cryo-EM) and atomic force microscopy (AFM) techniques were employed to capture images of nanoplexes. These images revealed the presence of individual nanoparticles measuring approximately 100–200 nm in contrast with the random distribution of clustered complexes observed in ultrasound-untreated samples of liposome nanoparticles and siRNA. AFU holds great potential as a standardized liposome processing and loading method because its process is fast, sterile, and does not require additional solvents.
Journal Article