Antibody drug conjugates (ADCs) normally compose of a humanized antibody and small molecular drug via a chemical linker. After decades of preclinical and clinical studies, a series of ADCs have been ...widely used for treating specific tumor types in the clinic such as brentuximab vedotin (Adcetris®) for relapsed Hodgkin's lymphoma and systemic anaplastic large cell lymphoma, gemtuzumab ozogamicin (Mylotarg®) for acute myeloid leukemia, ado-trastuzumab emtansine (Kadcyla®) for HER2-positive metastatic breast cancer, inotuzumab ozogamicin (Besponsa®) and most recently polatuzumab vedotin-piiq (Polivy®) for B cell malignancies. More than eighty ADCs have been investigated in different clinical stages from approximately six hundred clinical trials to date. This review summarizes the key elements of ADCs and highlights recent advances of ADCs, as well as important lessons learned from clinical data, and future directions.
Antibody drug conjugates (ADCs), normally composed of a humanized antibody and small molecular drugs via chemical linkers, represent a rapidly growing field for cancer therapy. In this review, we provide an overview of ADCs in preclinical and clinical development, as well as future directions of ADCs. Display omitted
Lipid-like nanoparticles (LLNs) have been extensively explored for messenger RNA (mRNA) delivery in various biomedical applications. However, the long-term storage of these nanoparticles is still a ...challenge for their clinical translation. In this study, we investigated a series of conditions for the long-term storage of LLNs with encapsulation of mRNA. We evaluated the stability of LLNs with different concentrations of cryoprotectants (sucrose, trehalose or mannitol) under the conditions of freezing or lyophilization processes. Through in vitro and in vivo mRNA delivery studies, we identified the optimal storage condition, and found that the addition with 5% (w/v) sucrose or trehalose to LLNs could remain their mRNA delivery efficiency for at least three months in the liquid nitrogen storage condition.
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•The stability of lipid-like nanoparticles (LLNs) are evaluated under aqueous, freezing, or lyophilization conditions.•Effects of cryoprotectants on LLNs stability are investigated with the freezing and lyophilization processes.•5% (w/v) sucrose or trehalose LLNs stored in liquid nitrogen remain mRNA delivery efficiency for over three months.
Atherosclerosis (AS), a chronic arterial disease, is the leading cause of death in western developed countries. Considering its long-term asymptomatic progression and serious complications, the early ...prevention and effective treatment of AS are particularly important. The unique characteristics of nanoparticles (NPs) make them attractive in novel therapeutic and diagnostic applications, providing new options for the treatment of AS. With the assistance of reactive oxygen species (ROS)-based NPs, drugs can reach specific lesion areas, prolong the therapeutic effect, achieve targeted controlled release and reduce adverse side effects. In this article, we reviewed the mechanism of AS and the generation and removal strategy of ROS. We further discussed ROS-based NPs, and summarized their biomedical applications in scavenger and drug delivery. Furthermore, we highlighted the recent advances, challenges and future perspectives of ROS-based NPs for treating AS.
Ultrasound with low frequency (20-100 kHz) assisted drug delivery has been widely investigated as a non-invasive method to enhance the permeability and retention effect of drugs. The functional ...micro/nanobubble loaded with drugs could provide an unprecedented opportunity for targeted delivery. Then, ultrasound with higher intensity would locally burst bubbles and release agents, thus avoiding side effects associated with systemic administration. Furthermore, ultrasound-mediated destruction of micro/nanobubbles can effectively increase the permeability of vascular membranes and cell membranes, thereby not only increasing the distribution concentration of drugs in the interstitial space of target tissues but also promoting the penetration of drugs through cell membranes into the cytoplasm. These advancements have transformed ultrasound from a purely diagnostic utility into a promising theragnostic tool. In this review, we first discuss the structure and generation of micro/nanobubbles. Second, ultrasound parameters and mechanisms of therapeutic delivery are discussed. Third, potential biomedical applications of micro/nanobubble-assisted ultrasound are summarized. Finally, we discuss the challenges and future directions of ultrasound combined with micro/nanobubbles.
Glioblastoma (GBM) is the most aggressive brain tumor, which owns the characteristics of high recurrence, low survival rate and poor prognosis because of the existence of blood brain barrier (BBB) ...and complicated brain tumor microenvironment. Currently, immunotherapy has attracted much attention on account of favorable therapeutic effect. In this study, we designed a cRGD-modified cancer cell membrane (CM) coated calcium carbonate nanoparticle to deliver interleukin-12 messenger RNA (IL-12 mRNA@cRGD-CM-CaCO
NPs). The cRGD-modified CM as the shell can endow the nanoparticles with BBB crossing and tumor homing/homotypic targeting effect in the brain tumor microenvironment. IL-12 mRNA-loaded calcium carbonate nanoparticles as the core allow synergistic immunotherapy of necroptosis-induced immune response and IL-12 mRNA transfection under ultrasound irradiation. The as-prepared biomimetic nanoparticles showed superior target and immunotherapeutic outcomes, suggesting that this biomimetic nanoplatform provides a feasible strategy for promoting BBB-penetrating and antitumor immunity.
With the development of nanomedicine technology, stimuli-responsive nanocarriers play an increasingly important role in antitumor therapy. Compared with the normal physiological environment, the ...tumor microenvironment (TME) possesses several unique properties, including acidity, high glutathione (GSH) concentration, hypoxia, over-expressed enzymes and excessive reactive oxygen species (ROS), which are closely related to the occurrence and development of tumors. However, on the other hand, these properties could also be harnessed for smart drug delivery systems to release drugs specifically in tumor tissues. Stimuli-responsive nanoparticles (srNPs) can maintain stability at physiological conditions, while they could be triggered rapidly to release drugs by specific stimuli to prolong blood circulation and enhance cancer cellular uptake, thus achieving excellent therapeutic performance and improved biosafety. This review focuses on the design of srNPs based on several stimuli in the TME for the delivery of antitumor drugs. In addition, the challenges and prospects for the development of srNPs are discussed, which can possibly inspire researchers to develop srNPs for clinical applications in the future.
Calcium carbonate nanoparticles have been widely used in biomedicine due to their biocompatibility and biodegradability. Recently, calcium carbonate nanoparticles are largely integrated with imaging ...contrast and therapeutic agents for various imaging and therapeutic approaches. In this review, we first described the advantages and preparation methods of calcium carbonate nanoparticles, then the state-of-the-art progress of calcium carbonate nanoparticles in diagnosis, treatment and theranostics was summarized. Finally, we discussed the challenges and recommendations for future studies of the calcium carbonate nanoparticles.
Platinum-based chemotherapy is used for non-small cell lung cancer (NSCLC). However, it has side effects and minimum efficacy against lung cancer metastasis. In this study, platinum–curcumin ...complexes were loaded into pH and redox dual-responsive nanoparticles (denoted as Pt–CUR@PSPPN) to facilitate intracellular release and synergistic anti-cancer effects. Pt–CUR@PSPPN was prepared by a nano-precipitation method and had a diameter of ∼100 nm. The nanoparticles showed increased anti-cancer effects both in vivo and in vitro. In addition, Pt–CUR@PSPPN blocked PI3K/AKT signal transduction pathway and inhibited MMP2 and VEGFR2, resulting in enhanced anti-metastatic activity. Furthermore, reduced side effects were also observed. In conclusion, Pt–CUR@PSPPN provided a novel and attractive therapeutic strategy for NSCLC.
Pt–CUR@PSPPN showed increased anti-cancer effects both in vitro and in vivo. The nanoparticles blocked PI3K/AKT signal transduction pathway and inhibited MMP2 and VEGFR2, resulting in enhanced anti-metastatic activity. In addition, reduced nephrotoxicity was also observed. Display omitted
Abstract Hepatocellular carcinoma (HCC) is a prevalent and lethal disease that is characterized by drug resistance. Doxorubicin (DOX) is a widely used chemotherapeutic drug and miR-375 has been shown ...to be a tumor suppressor in HCC. Here, we reported that miR-375 and DOX co-loaded into lipid-coated calcium carbonate nanoparticles (LCC-DOX/miR-375 NPs), enhanced the anti-tumor effects through combination therapy, and were highly effective in reversing drug resistance in HCC. LCC-DOX/miR-375 NPs were prepared by a reverse microemulsions method. In vitro , LCC-DOX/miR-375 NPs exhibited enhanced intracellular accumulation, pH-sensitive DOX release and potent cytotoxicity. In vivo , LCC-DOX/miR-375 NPs showed efficient antitumor effect both in xenograft and primary HCC murine models. Our results showed that the LCC-DOX/miR-375 nanoparticles provide a novel strategy to overcome the drug resistance and promote addictive effect between miR-375 and DOX in HCC.
In the wake of frequent and intensive human activities, highly urbanized areas consistently grapple with severe water environmental challenges. It becomes imperative to establish corresponding water ...environment models for simulating and forecasting regional water quality, addressing the associated environmental risks. The distributed framework water environment modeling system (DF-WEMS) incorporates fundamental principles, including the distributed concept and node concentration mass conservation. It adeptly merges point source and non-point source pollution load models with zero-dimensional, one-dimensional, and two-dimensional water quality models. This integration is specifically tailored for various Hydrological Feature Units (HFUs), encompassing lakes, reservoirs, floodplains, paddy fields, plain rivers, and hydraulic engineering structures. This holistic model enables the simulation and prediction of the water environment conditions within the watershed. In the Taihu Lake basin of China, a highly urbanized region featuring numerous rivers, lakes and gates, the DF-WEMS is meticulously constructed, calibrated, and validated based on 26 key water quality monitoring stations. The results indicate a strong alignment between the simulation of water quality indicators (WQIs) and real-world conditions, demonstrating the model’s reliability. This model proves applicable to the simulation, prediction, planning, and management of the water environment within the highly urbanized watershed.
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