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Improving the Phototherapeutic Efficiencies of Molecular and Nanoscale Materials by Targeting Mitochondria
摘要： Mitochondria-targeted cancer phototherapy (PT), which works by delivering photoresponsive agents specifically to mitochondria, is a powerful strategy to improve the phototherapeutic efficiency of anticancer treatments. Mitochondria play an essential role in cellular apoptosis, and are relevant to the chemoresistance of cancer cells. Furthermore, mitochondria are a major player in many cellular processes and are highly sensitive to hyperthermia and reactive oxygen species. Therefore, mitochondria serve as excellent locations for organelle-targeted phototherapy. In this review, we focus on the recent advances of mitochondria-targeting materials for mitochondria-specific PT. The combination of mitochondria-targeted PT with other anticancer strategies is also summarized. In addition, we discuss both the challenges currently faced by mitochondria-based cancer PT and the promises it holds.
关键词： PDT,PTT,subcellular organelle-targeting,cancer therapy,nanomedicine
更新于2025-09-10 09:29:36
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Doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer
摘要： Despite significant progress in the field of oncology, cancer remains one of the leading causes of death. Chemotherapy is one of the most common treatment options for cancer patients but is well known to result in off-target toxicity. Theranostic nanomedicines that integrate diagnostic and therapeutic functions within an all-in-one platform can increase tumor selectivity for more effective chemotherapy and aid in diagnosis and monitoring of therapeutic responses. Material and methods: In this work, theranostic nanoparticles were synthesized with commonly used biocompatible and biodegradable polymers and used as cancer contrast and therapeutic agents for optical imaging and treatment of breast cancer. These core–shell nanoparticles were prepared by nanoprecipitation of blends of the biodegradable and biocompatible amphiphilic copolymers poly(lactic-co-glycolic acid)-b-poly-l-lysine and poly(lactic acid)-b-poly(ethylene glycol). Poly-l-lysine in the first copolymer was covalently decorated with near-infrared fluorescent Alexa Fluor 750 molecules. Results: The spherical nanoparticles had an average size of 60–80 nm. The chemotherapeutic drug doxorubicin was encapsulated in the core of nanoparticles at a loading of 3% (w:w) and controllably released over a period of 30 days. A 33-fold increase in near-infrared fluorescence, mediated by protease-mediated cleavage of the Alexa Fluor 750-labeled poly-l-lysine on the surface of the nanoparticles, was observed upon interaction with the model protease trypsin. The cytocompatibility of drug-free nanoparticles and growth inhibition of drug-loaded nanoparticles on MDA-MB-231 breast cancer cells were investigated with a luminescence cell-viability assay. Drug-free nanoparticles were found to cause minimal toxicity, even at high concentrations (0.2–2,000 μg/mL), while doxorubicin-loaded nanoparticles significantly reduced cell viability at drug concentrations .10 μM. Finally, the interaction of the nanoparticles with breast cancer cells was studied utilizing fluorescence microscopy, demonstrating the potential of the nanoparticles to act as near-infrared fluorescence optical imaging agents and drug-delivery carriers. Conclusion: Doxorubicin-loaded, enzymatically activatable nanoparticles of less than 100 nm were prepared successfully by nanoprecipitation of copolymer blends. These nanoparticles were found to be suitable as controlled drug delivery systems and contrast agents for imaging of cancer cells.
关键词： enzymatic activation,nanoprecipitation,theranostics,PEG,poly-l-lysine,PLGA,block copolymers,nanomedicine,fluorescence imaging,drug delivery,nanoparticles,PLA
更新于2025-09-10 09:29:36
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Hybrid Nanostructures for Cancer Theranostics || Nanostructures for Externally Triggered Chemo/Thermal Therapies
摘要： Cancer is the most common cause of death globally despite improvement in early detection, life-style changes, and advances in radiotherapy, immunotherapy, chemotherapy, and molecular medicine. The American Cancer Society estimated 1,688,780 cases of cancer and 600,920 deaths in the USA in 2017 alone. Problems with current therapies include: invasive procedures, systemic side effects from the nonspecific nature of chemotherapy drugs, and drug-resistant tumors. In addition to limited efficacy, the side effects of current treatments include anemia, bleeding or clotting, loss of bone density, bowel dysfunction, fatigue, hair loss, damage to the heart, immune suppression, infertility, lung dysfunction, lymphedema, mental deficits, nausea, pain, sexual dysfunction, skin changes, weight loss or gain, and urinary and bladder problems. Radiation and chemotherapies comprise the bulk of cancer treatment methods in current practice, and the off-target effects are primarily due to the nonspecific toxicity of these methods. Obviously, limiting nonspecific toxicity will improve patients’ quality of life, while not affecting tumor directed dose—this provides the motivation to pursue tumor-targeted nanomedicine. Further, many current therapy methods do not adequately address the individual patient differences resulting from inter and intra-tumor heterogeneity. Ideal disease treatment would noninvasively deliver therapy to only the target, limiting side effects due to the nonspecific drug action, and expose the tumor to a sufficient amount of drug, or other therapy such as heat or radiation. Multifunctional nanoparticles (NPs), which aid in the diagnosis (generally by acting as a contrast agent for traditional diagnostic imaging modalities), possibly targeted to the specific molecular phenotype of tumors, and which also deliver therapy (nanotheranostics) offer benefits not possible with other therapies. Only about 1% of current therapeutic agents deposit in tumors; thus, the vast majority of injected drugs are either excreted or end up in undesired tissues. In addition to not effectively treating the disease, exposing the tumors to such low concentrations of chemotherapeutic agents also artificially selects for cells that can tolerate the drug, leading to resistance. Incorporating drugs into nanoconstructs that can be noninvasively tracked for delivery to the tumor and activated at the disease site, offers a potential solution to both the drug-delivery and toxicity/efficacy problems of current chemotherapies. Besides drug delivery, NPs can also be designed and used to thermally ablate the tumor using energy from an external source, thereby avoiding invasive surgical procedures. The subcellular size (in the tens to hundreds of nanometers, similar in size to organelles) of NPs makes them exceptionally well suited for use in drug delivery and/or as absorbers for certain wavelengths of light. They can circulate for a relatively long period because they avoid rapid filtration by the spleen and can pass through Kupffer cell sieve plates. A long circulation time gives them a greater percentage of injected dose accumulating in the desired location. Tumors generally exhibit a more porous vasculature and poorer lymphatic circulation than normal tissue, allowing more and larger particles to cross over between the blood vessels and intercellular space and build up there. This is called enhanced permeability and retention (EPR), and can cause NPs to build up in the tumor, provided they can circulate long enough.
关键词： Drug delivery,Cancer,Thermal ablation,Enhanced permeability and retention (EPR),Externally triggered NPs,Nanotheranostics,Nanomedicine
更新于2025-09-10 09:29:36
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[Methods in Molecular Biology] Atomic Force Microscopy Volume 1886 (Methods and Protocols) || Molecular Recognition Force Spectroscopy for Probing Cell Targeted Nanoparticles In Vitro
摘要： In the development and design of cell targeted nanoparticle-based systems the density of targeting moieties plays a fundamental role in allowing maximal cell-specific interaction. Here, we describe the use of molecular recognition force spectroscopy as a valuable tool for the characterization and optimization of targeted nanoparticles toward attaining cell-specific interaction. By tailoring the density of targeting moieties at the nanoparticle surface, one can correlate the unbinding event probability between nanoparticles tethered to an atomic force microscopy tip and cells to the nanoparticle vectoring capacity. This novel approach allows for a rapid and cost-effective design of targeted nanomedicines reducing the need for long and tedious in vitro tests.
关键词： Targeted nanoparticles,Tailored nanomedicine,Tip functionalization,Single molecule force spectroscopy,Drug delivery
更新于2025-09-09 09:28:46
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Personalized nanomedicine: a rapid, sensitive, and selective UV–vis spectrophotometry method for the quantification of nanostructured PEG-asparaginase activity in children’s plasma
摘要： PEGylated asparaginase (PEG-ASNase), which hydrolyzes asparagine to ammonia and aspartic acid, is an effective nanostructured antitumor agent for acute lymphoblastic leukemia (ALL). In order to monitor the activity of PEG-ASNase in plasma and design an individualization project, a rapid and sensitive method to determine PEG-ASNase activity in plasma using ultraviolet–visible spectrophotometry was established. Methods: PEG-ASNase is commonly used in acute lymphoblastic leukemia. With Nessler’s reagent as the chromogenic reagent of ammonia, a stable yellow complex was produced. The units of enzyme activity were defined as micromoles of ammonia released per minute. Results: Calibration curves fitted by plotting the OD at 450 nm of the Nessler product vs concentration were linear in the range of 27.8–1,111.0 IU/L with r2=0.999. The lower limit of quantification for PEG-ASNase activity in human plasma was 20 IU/L with good accuracy and precision. The intra- and interday precision (relative standard deviation) values were below 10% and accuracy ranged from 90% to 110% at all quality control levels. Analytical recoveries were determined between 90% and 110% for all quality control samples. Conclusion: This study proved that the Nessler method is well validated and can be successfully applied in the determination of plasma samples in the clinical setting for patients with ALL. It takes personalized nanomedicine to an entirely new level.
关键词： PEG-ASNase,plasma,ALL,enzyme activity,Nessler method,personalized nanomedicine,UV–vis spectrophotometry,Nessler’s reagent
更新于2025-09-09 09:28:46
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Nanosonosensitizers for Highly Efficient Sonodynamic Cancer Theranostics
摘要： Background: Multifunctional nanoplatforms with diagnostic-imaging and targeted therapeutic functionality (theranostics) are of great interest in the field of precision nanomedicine. The emerging sonodynamic therapy (SDT) combined with sonosensitizers under the guidance of photoacoustic (PA) imaging is highly expected to accurately eliminate cancer cells/tissue. Methods: Unique core/shell-structured theranostic FA-HMME-MNPs-PLGA nanoparticles (FHMP NPs, FA: folate, HMME: hematoporphyrin monomethyl ether, MNPs: melanin nanoparticles, PLGA: poly (lactic-co-glycolic) acid) were constructed by the integration of MNPs (for PA imaging) in the core and HMME in the shell for enhanced PA imaging-guided SDT, which were further functionalized with a tumor-targeting ligand, FA. The PA imaging-guided SDT was systematically and successfully demonstrated both in vitro and in vivo. The high biosafety of FHMP NPs was also systematically evaluated. Results: The synthesized FHMP NPs with a broad optical absorption not only possess high PA-imaging contrast enhancement capability but also exhibit significant SDT efficiency. Importantly, such a PLGA based nanoplatform improved light stability of HMME, enhancing sonodynamic performance and facilitated delivery of MNPs to the tumor region. Meanwhile, a combined effect between HMME and MNPs was discovered and verified. Furthermore, a sonosensitizer assisted by ultrasound irradiation engenders reactive oxygen species (ROS)-mediated cytotoxicity toward tumor cells/tissue. Both in vitro cell-level and systematic in vivo xenograft evaluations on tumor-bearing mice demonstrated that the selective killing effect of ROS on tumor cells was assisted by FHMP NPs, which played an active role in the suppression of tumor growth with high biosafety. Conclusion: A theranostic nanoplatform was successfully constructed, achieving PA imaging-guided SDT against breast cancer cells/tissue. More importantly, MNPs and HMME in one platform with combined effect for enhancing PA imaging was demonstrated. This unique theranostic nanoplatform with multiple capabilities paves a new way toward personalized medicine by rational utilization.
关键词： Nanosonosensitizers,Nanomedicine,Sonodynamic therapy,Photoacoustic imaging,HMME,Melanin
更新于2025-09-09 09:28:46
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In vivo and in vitro demonstration of gold nanorod aided photothermal pre-softening of B16F10 melanoma for efficient chemotherapy using Doxorubicin loaded Graphene Oxide
摘要： A combined photothermal therapy (PTT), and chemotherapy (chemo) was performed in vitro on B16F10 melanoma cells, and in vivo using melanoma bearing C57BL/6 mice. 785 nm (100 mW) irradiated gold nanorods (AuNRs) was used as the PT agent, and electrostatically conjugated Doxorubicin (Dox) to a nanocarrier graphene oxide (GO) worked as the chemotherapeutic. Selection of dosage was optimized from the individual viability studies, and finally a combined therapeutic (AuNR (100 ppm), GO (125, and 250 ppm), Dox (0.0058, and 0.00058 ppm)), was delivered in vitro. PTT, followed by chemo, sequentially, resulted in <10 % viability, whereas simultaneous PTT with chemo resulted in a viability of ~40 % for the melanoma cells. Flow cytometry indicated optical inhomogeneity in the cells that internalized GO, and AuNR, however, the Dox amount was identical within the cells treated with or without PTT. Confocal microscopy revealed that GO-Dox was internalized, and Dox was distributed uniformly within the cells irrespective of the treatment protocol. In vivo results in melanoma bearing C57BL/6 mice resembled the in vitro data closely. The tumor growth inhibition index was highest at 0.78 for the group receiving sequential treatment, followed by 0.61 for those receiving simultaneous treatment, where the control group had a score of 0. For the sequential treatment, pre-softening of the cells with PTT, followed by the chemo resulted in significantly improved toxicity of the treatment, whereas simultaneous PTT, with chemo results were dominated by the Dox alone.
关键词： Nanomedicine,Graphene Oxide,Photothermal therapy,Melanoma,Drug delivery,Gold Nanorods
更新于2025-09-04 15:30:14
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OPTIMIZATION OF GREEN SYNTHESIZED SILVER NANOPARTICLES FROM CARALLUMA UMBELLATA
摘要： Objective: The current study focuses on optimization and ecologically innocuous green synthesis of silver nanoparticles (AgNPs) using tribal plant Caralluma umbellata and to study its potential as an antibacterial and antifungal agent. Methods: The synthesis of AgNPs were confirmed by the colour change of the stem extract from yellow to dark brown and by UV-Visible spectroscopy. The optimum conditions for synthesis of AgNPs were analysed using Response surface methodology (RSM) based Box-Behnken design (BBD) using Design Expert software (7.0.0 trial version). The AgNPs synthesized were characterized by Scanning electron microscope (SEM), Energy dispersive X-ray (EDX), Fourier transform infrared (FTIR) and X-ray diffraction (XRD) analysis. Further, antibacterial and antifungal activity were performed using well diffusion method for both plant extract and AgNPs. Results: The UV-Visible spectrum of AgNPs revealed characteristic peak at 425.5 nm. The crystalline nature of synthesized AgNPs was confirmed by XRD with average size 26 nm. SEM confirms the spherical shape of AgNPs and by EDX the presence of elemental silver was observed. The ability of the plant to produce both reducing and capping agents were confirmed by FTIR. The optimum conditions for synthesis of AgNPs were found to be 0.55 mmol AgNO3 concentration, 45 °C temperature and 24h reaction time. Both plant sample and synthesized AgNPs exhibited good antimicrobial activity where AgNPs showed superior efficacy as an antimicrobial agent over the other. Conclusion: From the results obtained, it can be deduced that both C. umbellata stem extract and synthesized AgNPs can act as potent antimicrobial agent. But the synthesized AgNPs is more potent against bacteria and fungus.
关键词： Nanomedicine,BBD,Antimicrobial agent,Tribal plant,Silver nanoparticles
更新于2025-09-04 15:30:14