Nanomedicines modulate the tumor immune microenvironment for cancer therapy.

Introduction: In recent years, the evolution of immunotherapy as a means to trigger a robust antitumor immune response has revolutionized cancer treatment. Despite its potential, the effectiveness of cancer immunotherapy is hindered by low response rates and significant systemic side effects. Nanotechnology emerges as a promising frontier in shaping the future of cancer immunotherapy.

Liposome biodistribution mapping with X-ray fluorescence imaging.

Lipid-based nanoparticles are organic nanostructures constituted of phospholipids and cholesterol, displaying high biocompatibility. They have been demonstrated as effective nanocarriers for drug delivery and targeting. Mapping liposome distribution is crucial as it enables a precise understanding of delivery kinetics, tissue targeting efficiency, and potential off-target effects.

Protamine-mediated efficient transcellular and transmucosal delivery of proteins.

Proteins and peptides often require frequent needle-based administrations. Here, we report a non-parenteral delivery method for proteins through physical mixing with protamine, an FDA-approved peptide. Protamine was shown to promote tubulation and rearrangement of cellular actin, leading to enhanced intracellular delivery of proteins compared to poly(arginine) (R8).

Chemically engineering the drug release rate of a PEG-paclitaxel conjugate using click and steric hindrance chemistries for optimal efficacy.

A small molecule drug with poor aqueous solubility can be conjugated to a hydrophilic polymer like poly(ethylene glycol) (PEG) to form an amphiphilic polymer-drug conjugate that self-assembles to form nanoparticles (NPs) with improved solubility and enhanced efficacy. This strategy has been extensively applied to improve the delivery of several small molecule drugs. However, very few reports have succeeded to tune the rate of drug release from these NPs.

Development of a child-friendly oral drug formulation using liposomal multilamellar vesicle technology.

Many medicines are only available in solid dosage forms suitable for adults, and extemporaneous compounding is required to prepare formulations for children. However, this common practice often results in inaccurate dosing and unpleasant taste, reducing the medication adherence. Here, we report the development of a new method to prepare and compound child-friendly oral formulations based on a liposomal multilamellar vesicle (MLV) platform.

Interplay between the linker and polymer molecular weight of a self-assembling prodrug on the pharmacokinetics and therapeutic efficacy.

Poorly water-soluble small hydrophobic compounds can be conjugated to a hydrophilic polymer such as methoxypolyethylene glycol (mPEG) to form amphiphilic prodrugs that can self-assemble into nanoparticles (NPs) with increased aqueous solubility, prolonged circulation, and improved delivery. There have been numerous reports utilizing this strategy to improve delivery of small molecule drugs, but few reports take systematic, structure-activity relationship (SAR)-based approaches to develop optimal prodrug conjugates. Additionally, it is important to study interplay of different components within the conjugate, such as polymer molecular weight (M.

Simultaneous Chromatographic Quantitation of Drug Substance and Excipients in Nanoformulations Using a Combination of Evaporative Light Scattering and Absorbance Detectors.

Nanomedicines including lipid- and polymer-based nanoparticles and polymer-drug conjugates enable targeted drug delivery for the treatment of numerous diseases. Quantitative analysis of components in nanomedicines is routinely performed to characterize the products to ensure quality and property consistency but has been mainly focused on the active pharmaceutical ingredients (APIs) in academic publications. It has been increasingly recognized that excipients in nanomedicines are critical in determining the product quality, stability, consistency, and safety.

Reversal of pancreatic desmoplasia by a tumour stroma-targeted nitric oxide nanogel overcomes TRAIL resistance in pancreatic tumours.

Objective: Stromal barriers, such as the abundant desmoplastic stroma that is characteristic of pancreatic ductal adenocarcinoma (PDAC), can block the delivery and decrease the tumour-penetrating ability of therapeutics such as tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), which can selectively induce cancer cell apoptosis. This study aimed to develop a TRAIL-based nanotherapy that not only eliminated the extracellular matrix barrier to increase TRAIL delivery into tumours but also blocked antiapoptotic mechanisms to overcome TRAIL resistance in PDAC.

Design: Nitric oxide (NO) plays a role in preventing tissue desmoplasia and could thus be delivered to disrupt the stromal barrier and improve TRAIL delivery in PDAC.

Liposomal Resiquimod for Enhanced Immunotherapy of Peritoneal Metastases of Colorectal Cancer.

Colorectal cancer with peritoneal metastases is currently treated by cytoreductive surgery and locoregional chemotherapeutics. This standard treatment is associated with high morbidity, mortality, and recurrence rate. To augment the existing therapy, we developed a liposome-based delivery system containing 1,2-stearoyl-3-trimethylammonium-propane chloride (DSTAP), a cationic lipid, to localize a toll-like receptor agonist, resiquimod (R848), in the peritoneal cavity (PerC) for enhancing the immune response against cancer that had spread to the PerC.

Altering the intra-liver distribution of phospholipid-free small unilamellar vesicles using temperature-dependent size-tunability.

We demonstrated that phospholipid-free small unilamellar vesicles (PFSUVs) composed of TWEEN 80 and cholesterol (25/75, mol%) could be fabricated using a staggered herringbone micromixer with precise controlling of their mean size between 54 nm and 147 nm. Increasing the temperature or decreasing the flow rate led to an increase in the resulting particle diameter. In zebrafish embryos, 120-nm PFSUVs showed 3-fold higher macrophage clearance compared to the 60-nm particles, which exhibited prolonged blood circulation.

Lipid-based nanoparticle technologies for liver targeting.

Liver diseases such as hepatitis, cirrhosis, and hepatocellular carcinoma are global health problems accounting for approximately 800 million cases and over 2 million deaths per year worldwide. Major drawbacks of standard pharmacological therapies are the inability to deliver a sufficient concentration of a therapeutic agent to the diseased liver, and nonspecific drug delivery leading to undesirable systemic side effects. Additionally, depending on the specific liver disease, drug delivery to a subset of liver cells is required.

Mechanical stretch induces hair regeneration through the alternative activation of macrophages.

Tissues and cells in organism are continuously exposed to complex mechanical cues from the environment. Mechanical stimulations affect cell proliferation, differentiation, and migration, as well as determining tissue homeostasis and repair. By using a specially designed skin-stretching device, we discover that hair stem cells proliferate in response to stretch and hair regeneration occurs only when applying proper strain for an appropriate duration.

Combined delivery of sorafenib and a MEK inhibitor using CXCR4-targeted nanoparticles reduces hepatic fibrosis and prevents tumor development.

Liver damage and fibrosis are precursors of hepatocellular carcinoma (HCC). In HCC patients, sorafenib-a multikinase inhibitor drug-has been reported to exert anti-fibrotic activity. However, incomplete inhibition of RAF activity by sorafenib may also induce paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in malignant cells.

Docetaxel-carboxymethylcellulose nanoparticles ameliorate CCl-induced hepatic fibrosis in mice.

Chronic liver diseases have recently garnered substantial attention as a leading cause of death around the world. During the progression of liver fibrosis/cirrhosis induced by chronic liver injury, hepatic stellate cells (HSCs) play key roles in the regulation of liver fibrogenesis and can even accelerate the progression of hepatocellular carcinoma (HCC). Thus, inhibition of HSC activation or suppression of inflammatory cytokine secretion by HSCs may be an efficient therapeutic strategy to ameliorate liver fibrosis/cirrhosis.