Recent advances of focused ultrasound induced blood-brain barrier opening for clinical applications of neurodegenerative diseases.

With the aging population on the rise, neurodegenerative disorders have taken center stage as a significant health concern. The blood-brain barrier (BBB) plays an important role to maintain the stability of central nervous system, yet it poses a formidable obstacle to delivering drugs for neurodegenerative disease therapy. Various methods have been devised to confront this challenge, each carrying its own set of limitations.

Polymer-DNA assembled nanoflower for targeted delivery of dolastatin-derived microtubule inhibitors.

Dolastatin derivatives possess excellent anticancer activity and have been translated into clinical trials for cancer therapy. Drug delivery systems enable dolastatin derivatives to break the limitation of instability during blood circulation and ineffective cell internalization in the application. Nevertheless, their potential has not been thoroughly established because of the limited loading efficacy and complicated chemical modification.

DNA self-assembly nanoflower reverse P-glycoprotein mediated drug resistance in chronic myelogenous leukemia therapy.

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder caused by the BCR-ABL chimeric tyrosine kinase. Vincristine (VCR) is widely used in leukemia therapy but is hindered by multidrug resistance (MDR). We prepared DNA nanoflower via self-assembly for the delivery of VCR and P-glycoprotein small interfering RNA (P-gp siRNA).

Ultrasound-assisted biomimetic nanobubbles for targeted treatment of atherosclerosis.

Cardiovascular disease caused by atherosclerosis remains the main reason of death in the worldwide scale. Although oxidative stress plays a key role in the initiation and progression of atherosclerosis, current antioxidant drugs have limited efficacy. To resolve this problem, we constructed Nox2 siRNA-loaded nanobubbles (PNBs-siNox2) coated with platelet membranes to utilize their antioxidant stress activity and targeting effect for atherosclerosis treatment.

Biomimetic calcium carbonate nanoparticles delivered IL-12 mRNA for targeted glioblastoma sono-immunotherapy by ultrasound-induced necroptosis.

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).

Recent Advances of Calcium Carbonate Nanoparticles for Biomedical Applications.

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.

Tumor Microenvironment-Based Stimuli-Responsive Nanoparticles for Controlled Release of Drugs in Cancer Therapy.

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.

Mechanistic Insights and Therapeutic Delivery through Micro/Nanobubble-Assisted Ultrasound.

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.

ROS-Based Nanoparticles for Atherosclerosis Treatment.

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.

Nanoparticle-Assisted Sonosensitizers and Their Biomedical Applications.

As a non-invasive strategy, sonodynamic therapy (SDT) which utilizes sonosensitizers to generate reactive oxygen species (ROS) has received significant interest over recent years due to its ability to break depth barrier. However, intrinsic limitations of traditional sonosensitizers hinder the widespread application of SDT. With the development of nanotechnology, various nanoparticles (NPs) have been designed and used to assist sonosensitizers for SDT.

Recent advances of antibody drug conjugates for clinical applications.

Antibody drug conjugates (ADCs) normally compose of a humanized antibody and small molecular drug 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.

Platinum complexes of curcumin delivered by dual-responsive polymeric nanoparticles improve chemotherapeutic efficacy based on the enhanced anti-metastasis activity and reduce side effects.

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.

Long-term storage of lipid-like nanoparticles for mRNA delivery.

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.

One-pot synthesis of a microporous organosilica-coated cisplatin nanoplatform for HIF-1-targeted combination cancer therapy.

Nanoparticle formulations have proven effective for cisplatin delivery. However, the development of a versatile nanoplatform for cisplatin-based combination cancer therapies still remains a great challenge. : In this study, we developed a one-pot synthesis method for a microporous organosilica shell-coated cisplatin nanoplatform using a reverse microemulsion method, and explored its application in co-delivering acriflavine (ACF) for inhibiting hypoxia-inducible factor-1 (HIF-1).

Biocompatible co-loading vehicles for delivering both nanoplatin cores and siRNA to treat hepatocellular carcinoma.

Bmi-1 is a gene related to malignant transformation in hepatocellular carcinoma (HCC). The liver cancer cells developed the ability to tolerate CDDP treatment with the elevation of Bmi-1. Bmi-1 is also an oncogene promoting malignance of tumor and an anti-cancer target in many studies.

Selenium-doped calcium carbonate nanoparticles loaded with cisplatin enhance efficiency and reduce side effects.

Osteosarcoma is the bone tumor that most commonly affects children and teenagers with low survival rate because of metastatic relapse or recurrence. Cisplatin is a first-line chemotherapy for osteosarcoma. However, severe side effects limit its use in clinic.

Enhancement of cisplatin efficacy by lipid-CaO nanocarrier-mediated comprehensive modulation of the tumor microenvironment.

Hypoxia, acidosis and high level of glutathione (GSH) are characteristic abnormalities of the tumor microenvironment (TME), which promote tumor progression, metastasis, and resistance to therapies. Previous attempts to improve therapeutic efficacy were limited to modifying individual TME elements. In this study, we proposed a comprehensive TME modulation strategy that modifies multiple elements of the TME in order to enhance cisplatin anticancer efficacy.

Synergism of cisplatin-oleanolic acid co-loaded calcium carbonate nanoparticles on hepatocellular carcinoma cells for enhanced apoptosis and reduced hepatotoxicity.

Cisplatin (CDDP), a widely used chemotherapeutic agent against hepatocellular carcinoma (HCC), faces severe resistance and hepatotoxicity problems which can be alleviated through combination therapy. The objective of this study was to develop a pH-dependent calcium carbonate nano-delivery system for the combination therapy of CDDP with oleanolic acid (OA). A microemulsion method was employed to generate lipid coated cisplatin/oleanolic acid calcium carbonate nanoparticles (CDDP/OA-LCC NPs), and the loading concentration of CDDP and OA was measured by atomic absorption spectroscopy and HPLC respectively.

Enhancing the therapeutic effect via elimination of hepatocellular carcinoma stem cells using Bmi1 siRNA delivered by cationic cisplatin nanocapsules.

Resistance of hepatocellular carcinoma (HCC) to systemic chemotherapy is partially due to presence of drug-resistant cancer stem cells. Bmi1 protein is essential for survival and proliferation of HCC cancer stem cells (CSCs). Here, we report that Bmi1 siRNA (Bmi1siR) loaded in cationic nanocapsules of cisplatin (NPC) eliminated stem cells in situ HCC in mice.

Cisplatin and curcumin co-loaded nano-liposomes for the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) continues to be a leading cause of cancer related death in the world. Conventional chemotherapeutic agents such as cisplatin (CDDP) have an unsatisfactory efficacy on HCC due to the poor response, severe toxicity and drug resistance. Curcumin (CUR) could improve the chemosensitivity of HCC to chemotherapy drugs by regulating a variety of signaling pathways.

Enhancing anti-tumor efficiency in hepatocellular carcinoma through the autophagy inhibition by miR-375/sorafenib in lipid-coated calcium carbonate nanoparticles.

Unlabelled: Sorafenib is a first-line drug for hepatocellular carcinoma (HCC). Autophagy has been shown to facilitate sorafenib resistance. miR-375 has been shown to be an inhibitor of autophagy.

Co-delivery of doxorubicin and imatinib by pH sensitive cleavable PEGylated nanoliposomes with folate-mediated targeting to overcome multidrug resistance.

Multidrug resistance to chemotherapeutic drugs is a major obstacle to breast cancer treatment. In this study, doxorubicin (DOX) and imatinib (IM) were co-loaded into folate receptor targeted (FR-targeted) pH-sensitive liposomes (denoted as FPL-DOX/IM) to fulfill intracellular acid-sensitive release and reverse drug resistance. FPL-DOX/IM could maintain stability in blood circulation with approximate diameters of 100 nm and rapidly release encapsulated drugs in tumor acidic microenvironment.

MiR-375 and Doxorubicin Co-delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma.

Doxorubicin (DOX) is one of the most frequently used anti-cancer drugs and the front line option for hepatocellular carcinoma (HCC) treatment. However, the clinical applications of DOX are restricted largely due to its toxicity and chemoresistance. Here, we report that miR-375 and DOX were co-delivered by liposomes (named L-miR-375/DOX-NPs) for combination therapy of HCC and drug resistance reversion of DOX.

MiR-375 delivered by lipid-coated doxorubicin-calcium carbonate nanoparticles overcomes chemoresistance in hepatocellular carcinoma.

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.

Nanocrystals of a new camptothecin derivative WCN-21 enhance its solubility and efficacy.

WCN-21 is a new camptothecin derivative we synthesized and has desirable anti-tumor efficacy, but its aqueous solubility is very low and hurdles the further evaluation and development. In this study, we prepared nanocrystals of WCN-21 through a bottom-up approach to enhance its solubility and obtained WCN-21 nanorods (WND) and nanospheres (WNP). We investigated the crystallization of WND and WNP in different temperature and solvents and found that both temperature and solvents affect the crystal shapes and sizes.