Turing miRNA into infinite coordination supermolecule: a general and enabling nanoengineering strategy for resurrecting nuclear acid therapeutics

Background Clinical translation of therapeutic nuclear acid, particularly those targeting tumor progression, has been hampered by the intrinsic weaknesses of nuclear acid therapeutic including poor systemic stability, rapid clearance, low membrane permeability and lack of targeting ability. Small nuclear acid engineered into carrier-free nanodrugs with structural stability and disease targeting may be viable to overcome pharmaceutical obstacles of nuclear acid. Methods A general method through a mild and simple chemistry was established to convert therapeutic miRNA into an infinite Auric-sulfhydryl coordination supramolecular miRNA termed IacsRNA with near-spherical nanostructure, high colloid as well as anti-hydrolysis stability and low macrophage uptakes. Results IacsRNA presented the increased half-life period in circulation and accumulation at tumor sites in comparison to normal miRNA. Moreover, Iacs-miR-30c showed no toxicity of viscera and sanguis system in the 5-time injection dosage of the treatment. More importantly, Iacs-miR-30c potently suppressed the Wnt signaling pathway in vitro and in vivo, and effectively sensitized both potency of 5-Fu in PDX model of colon cancer and Anti-PD1 in B16F10 homograft model of melanoma. Conclusion Collectively, this work amply confirmed the design of IacsRNA as a general and viable strategy of nano-pharmaceutic to concert flimsy therapeutic miRNA into potential drugs. Considering from a broader perspective, the miRNA-initiated infinite coordination self-assembly strategy has distinct advantages in resurrecting nuclear acid therapeutics, probably bringing new inspiration to RNA-derived therapeutics of a great variety of human diseases including cancer. Graphical Abstract

Binary Dimeric Prodrug Nanoparticles for Self-Boosted Drug Release and Synergistic Chemo-Photodynamic Therapy

Chemotherapy is the major strategy for cancer therapy, but its limited therapeutic efficiency and serious toxicity to normal tissues greatly restrict its clinical performance. Herein, we develop carrier-free self-activated prodrug...

Enhanced Photothermal Heating and Combination Therapy of NIR Dye via Conversion to Self-Assembled Ionic Nanomaterials

Combination nanodrugs are promising therapeutic agents for cancer treatment. However, they often require the use of complex nanovehicles for transportation into the tumor site. Herein, a new class of carrier-free...

Cross-Linked Enzyme Aggregates and Their Application in Enzymatic Pretreatment of Microalgae: Comparison Between CLEAs and Combi-CLEAs

Carrier-free immobilization is a key process to develop efficient biocatalysts able to catalyze the cell wall degradation in microalgae where the traditional solid supports cannot penetrate. Thus, the insolubilization of commercial Celluclast®, Alcalase®, and Viscozyme® enzymes by carrier-free immobilization and their application in microalgae pretreatment was investigated. In this study, different precipitants at different ratios (ethanol, acetone, and polyethylene glycol 4000) were tested in the first part of the method, to establish the precipitation conditions. The screening of the best precipitant is needed as it depends on the nature of the enzyme. The best results were studied in terms of immobilization yield, thermal stability, and residual activity and were analyzed using scanning electron microscopy. Moreover, a novel strategy was intended including the three enzymes (combi-CLEAs) to catalyze the enzymatic degradation of Nannochloropsis gaditana microalgal cell wall in one pot. The carrier-free immobilized derivatives were 10 times more stable compared to soluble enzymes under the same. At the best conditions showed its usefulness in the pretreatment of microalgae combined with ultrasounds, facilitating the cell disruption and lipid recovery. The results obtained suggested the powerful application of these robust biocatalysts with great catalytic properties on novel and sustainable biomass such as microalgae to achieve cost-effective and green process to extract valuable bioactive compounds.

Research Progress of Carrier-Free Antitumor Nanoparticles Based on Phytochemicals

Cancer is a major worldwide public health issue, responsible for millions of deaths every year. Cancer cases and deaths are expected to increase rapidly with population growth, age, and lifestyle behaviors that increase cancer risk. Long-term chemotherapy results in acquired drug resistance. Traditional treatment methods have limitations and cannot effectively treat distal metastatic cancers. Application of nanocarriers in multi-chemotherapy must be promoted. With research progress, the shortcomings of traditional nanocarriers have gradually become evident. Carrier-free nanodrugs with desirable bioactivity have attracted considerable attention. In this review, we provide an overview of recent reports on several carrier-free nanodrug delivery systems based on phytochemicals. This review focuses on the advantages of carrier-free nanodrugs, and provides new insights for establishment of ideal cancer treatment nanosystems.