Engineering hairy cellulose nanocrystals for chemotherapy drug capture.

Cancer is one of the leading causes of death worldwide, affecting millions of people every year. While chemotherapy remains one of the most common cancer treatments in the world, the severe side effects of chemotherapy drugs impose serious concerns to cancer patients. In many cases, the chemotherapy can be localized to maximize the drug effects; however, the drug systemic circulation induces undesirable side effects. Here, we have developed a highly efficient cellulose-based nanoadsorbent that can capture more than 6000 mg of doxorubicin (DOX), one of the most widely used chemotherapy drugs, per gram of the adsorbent at physiological conditions. Such drug capture capacity is more than 3200% higher than other nanoadsorbents, such as DNA-based platforms. We show how anionic hairy cellulose nanocrystals, also known as electrosterically stabilized nanocrystalline cellulose (ENCC), bind to positively charged drugs in human serum and capture DOX immediately without imposing any cytotoxicity and hemolytic effects. We elucidate how ENCC provides a remarkable platform for biodetoxification at varying pH, ionic strength, ion type, and protein concentration. The outcome of this research may pave the way for developing the next generation in vitro and in vivo drug capture additives and devices.

Supramolecular Nanosubstrate-Mediated Delivery for CRISPR/Cas9 Gene Disruption and Deletion.

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) is an efficient and precise gene-editing technology that offers a versatile solution for establishing treatments directed at genetic diseases. Currently, CRISPR/Cas9 delivery into cells relies primarily on viral vectors, which suffer from limitations in packaging capacity and safety concerns. These issues with a nonviral delivery strategy are addressed, where Cas9•sgRNA ribonucleoprotein (RNP) complexes can be encapsulated into supramolecular nanoparticles (SMNP) to form RNP⊂SMNPs, which can then be delivered into targeted cells via supramolecular nanosubstrate-mediated delivery. Utilizing the U87 glioblastoma cell line as a model system, a variety of parameters for cellular-uptake of the RNP-laden nanoparticles are examined. Dose- and time-dependent CRISPR/Cas9-mediated gene disruption is further examined in a green fluorescent protein (GFP)-expressing U87 cell line (GFP-U87). The utility of an optimized SMNP formulation in co-delivering Cas9 protein and two sgRNAs that target deletion of exons 45-55 (708 kb) of the dystrophin gene is demonstrated. Mutations in this region lead to Duchenne muscular dystrophy, a severe genetic muscle wasting disease. Efficient delivery of these gene deletion cargoes is observed in a human cardiomyocyte cell line (AC16), induced pluripotent stem cells, and mesenchymal stem cells.

Cross-Linked Fluorescent Supramolecular Nanoparticles for Intradermal Controlled Release of Antifungal Drug-A Therapeutic Approach for Onychomycosis.

The existing approaches to onychomycosis demonstrate limited success since the commonly used oral administration and topical cream only achieve temporary effective drug concentration at the fungal infection sites. An ideal therapeutic approach for onychomycosis should have (i) the ability to introduce antifungal drugs directly to the infected sites; (ii) finite intradermal sustainable release to maintain effective drug levels over prolonged time; (iii) a reporter system for monitoring maintenance of drug level; and (iv) minimum level of inflammatory responses at or around the fungal infection sites. To meet these expectations, we introduced ketoconazole-encapsulated cross-linked fluorescent supramolecular nanoparticles (KTZ⊂c-FSMNPs) as an intradermal controlled release solution for treating onychomycosis. A two-step synthetic approach was adopted to prepare a variety of KTZ⊂c-FSMNPs. Initial characterization revealed that 4800 nm KTZ⊂c-FSMNPs exhibited high KTZ encapsulation efficiency/capacity, optimal fluorescent property, and sustained KTZ release profile. Subsequently, 4800 nm KTZ⊂c-FSMNPs were chosen for in vivo studies using a mouse model, wherein the KTZ⊂c-FSMNPs were deposited intradermally via tattoo. The results obtained from (i) in vivo fluorescence imaging, (ii) high-performance liquid chromatography quantification of residual KTZ, (iii) matrix-assisted laser desorption/ionization mass spectrometry imaging mapping of KTZ distribution in intradermal regions around the tattoo site, and (iv) histology for assessment of local inflammatory responses and biocompatibility, suggest that 4800 nm KTZ⊂c-FSMNPs can serve as an effective treatment for onychomycosis.