A Machine Learning-Optimized System for Pulsatile, Photo- and Chemotherapeutic Treatment Using Near-Infrared Responsive MoS-Based Microparticles in a Breast Cancer Model.

Multimodal cancer therapies are often required for progressive cancers due to the high persistence and mortality of the disease and the negative systemic side effects of traditional therapeutic methods. Thus, the development of less invasive modalities for recurring treatment cycles is of clinical significance. Herein, a light-activatable microparticle system was developed for localized, pulsatile delivery of anticancer drugs with simultaneous thermal ablation by applying controlled ON-OFF thermal cycles using near-infrared laser irradiation.

A microneedle vaccine printer for thermostable COVID-19 mRNA vaccines.

Decentralized manufacture of thermostable mRNA vaccines in a microneedle patch (MNP) format could enhance vaccine access in low-resource communities by eliminating the need for a cold chain and trained healthcare personnel. Here we describe an automated process for printing MNP Coronavirus Disease 2019 (COVID-19) mRNA vaccines in a standalone device. The vaccine ink is composed of lipid nanoparticles loaded with mRNA and a dissolvable polymer blend that was optimized for high bioactivity by screening formulations in vitro.

Virus-Mimicking Polymer Nanoparticles Targeting CD169 Macrophages as Long-Acting Nanocarriers for Combination Antiretrovirals.

Monosialodihexosylganglioside (GM3)-presenting lipid-coated polymer nanoparticles (NPs) that recapitulate the sequestration of human immunodeficiency virus-1 (HIV-1) particles in CD169 virus-containing compartments (VCCs) of macrophages were developed as carriers for delivery and sustained release of a combination of two antiretrovirals (ARVs), rilpivirine (RPV) and cabotegravir (CAB). RPV and CAB were co-loaded into GM3-presenting lipid-coated polylactic acid (PLA) and poly(lactic--glycolic acid) (PLGA) NPs without loss in potency of the drugs. GM3-presenting PLA NPs demonstrated the most favorable release properties and achieved inhibition of HIV-1 infection of primary human macrophages for up to 35 days.

Stiffness of HIV-1 Mimicking Polymer Nanoparticles Modulates Ganglioside-Mediated Cellular Uptake and Trafficking.

The monosialodihexosylganglioside, GM3, and its binding to CD169 (Siglec-1) have been indicated as key factors in the glycoprotein-independent sequestration of the human immunodeficiency virus-1 (HIV-1) in virus-containing compartments (VCCs) in myeloid cells. Here, lipid-wrapped polymer nanoparticles (NPs) are applied as a virus-mimicking model to characterize the effect of core stiffness on NP uptake and intracellular fate triggered by GM3-CD169 binding in macrophages. GM3-functionalized lipid-wrapped NPs are assembled with poly(lactic--glycolic) acid (PLGA) as well as with low and high molecular weight polylactic acid (PLA and PLA) cores.

Physiologically Relevant Mechanics of Biodegradable Polyester Nanoparticles.

Despite the extensive use of biodegradable polyester nanoparticles for drug delivery, and reports of the strong influence of nanoparticle mechanics on nano-bio interactions, there is a lack of systematic studies on the mechanics of these nanoparticles under physiologically relevant conditions. Here, we report indentation experiments on poly(lactic acid) and poly(lactide--glycolide) nanoparticles using atomic force microscopy. While dried nanoparticles were found to be rigid at room temperature, their elastic modulus was found to decrease by as much as 30 fold under simulated physiological conditions (i.

Membrane-wrapped nanoparticles probe divergent roles of GM3 and phosphatidylserine in lipid-mediated viral entry pathways.

Gold nanoparticles (NPs) wrapped in a membrane can be utilized as artificial virus nanoparticles (AVNs) that combine the large nonblinking or bleaching optical cross-section of the NP core with the biological surface properties and functionalities provided by a self-assembled lipid membrane. We used these hybrid nanomaterials to test the roles of monosialodihexosylganglioside (GM3) and phosphatidylserine (PS) for a lipid-mediated targeting of virus-containing compartments (VCCs) in macrophages. GM3-presenting AVNs bind to CD169 (Siglec-1)-expressing macrophages, but inclusion of PS in the GM3-containing AVN membrane decreases binding.