The current study examined the effects of honey solution and water access on feeding behavior and survival of starving solenopsis mealybugs, Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae). The electrical penetration graph technique and an artificial membrane system were used to check whether P. solenopsis could imbibe free water or other liquid, such as the honey solution used here, in its natural environment. The recorded electrical penetration graph waveforms revealed that P. solenopsis could continuously imbibe water-honey solution for several hours, which indicated that honey solution and water acquisition could possibly occur when P. solenopsis had access to such liquids in its natural environment. Waveforms of water-honey solution feeding alternated between two distinct feeding phases in a regular pattern, which was assumed to reflect inherent habits of feeding attempts. The effects of honey solution and water acquisition on survival of P. solenopsis was also examined. Comparison between P. solenopsis in different treatments (starved, water feeding, honey solution feeding, and cotton plant feeding) suggested that 1) P. solenopsis could accept but did not favor feeding on water or the honey solution, and 2) this feeding could prolong its survival, but had no effect on body size.

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Poor drug penetration into tumor cells and tissues is a worldwide difficulty in cancer therapy. A strategy is developed for virion-like membrane-breaking nanoparticles (MBNs) to smoothly accomplish tumor-activated cell-and-tissue dual-penetration for surmounting impermeable drug-resistant cancer. Tailor-made dendritic arginine-rich peptide prodrugs are designed to mimic viral protein transduction domains and globular protein architectures. Attractively, these protein mimics self-assemble into virion-like nanoparticles in aqueous solution, having highly ordered secondary structure. Tumor-specific acidity conditions would activate the membrane-breaking ability of these virion-like nanoparticles to perforate artificial and natural membrane systems. As expected, MBNs achieve highly efficient drug penetration into drug-resistant human ovarian (SKOV3/R) cancer cells. Most importantly, the well-organized MBNs can pass through endothelial/tumor cells and spread from one cell to another one. Intravenous injection of MBNs into nude mice bearing impermeable SKOV3/R tumors suggests that the MBNs can recognize the tumor tissue after prolonged blood circulation, evoke the membrane-breaking function for robust transvascular extravasation, and penetrate into the deep tumor tissue. This work provides the first demonstration of sophisticated molecular and supramolecular engineering of virion-like MBNs to realize the long-awaited cell-and-tissue dual-penetration, contributing to the development of a brand-new avenue for dealing with incurable cancers.

Chemotherapy resistance remains a serious impediment to successful antitumor therapy around the world. However, existing chemotherapeutic approaches are difficult to cope with the notorious multidrug resistance in clinical treatment. Herein, we developed tumor-specific multiple stimuli-activated dendrimeric nanoassemblies with a metabolic blockade to completely combat both physiological barriers and cellular factors of multidrug resistance. With a sophisticated molecular and supramolecular engineering, this type of tumor-specific multiple stimuli-activated nanoassembly based on dendrimeric prodrugs can hierarchically break through the sequential physiological barriers of drug resistance, including stealthy dendritic PEGylated corona to optimize blood transportation, robust nanostructures for efficient tumor passive targeting and accumulation, enzyme-activated tumor microenvironment targeted to deepen tumor penetration and facilitate cellular uptake, cytoplasmic redox-sensitive disintegration for sufficient release of encapsulated agents, and lysosome acid-triggered nucleus delivery of antitumor drugs. In the meantime, we proposed a versatile tactic of a tumor-specific metabolism blockade for provoking several pathways (ATP restriction, apoptotic activation, and anti-apoptotic inhibition) to restrain multiple cellular factors of drug resistance. The highly efficient antitumor activity to drug-resistant MCF-7R tumor in vitro and in vivo supports this design and strongly defeats both physiological barriers and cellular factors of chemotherapy resistance. This work sets up an innovative dendrimeric nanosystem to surmount multidrug resistance, contributing to the development of a comprehensive nanoparticulate strategy for future clinical applications.

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Herein, multifunctional mimics of viral architectures and infections self‐assembled from tailor‐made dendritic lipopeptides for programmed targeted drug delivery are reported. These viral mimics not only have virus‐like components and nanostructures, but also possess virus‐like infections to solid tumor and tumor cells. Encouragingly, the viral mimics provide the following distinguished features for tumor‐specific systemic delivery: i) stealthy surface to resist protein interactions and prolong circulation time in blood, ii) well‐defined nanostructure for passive targeting to solid tumor site, iii) charge‐tunable shielding for tumor extracellular pH targeting, iv) receptor‐mediated targeting to enhance tumor‐specific uptake, and v) supramolecular lysine‐rich architectures mimicking viral subcellular targeting for efficient endosomal escape and nuclear delivery. This bioinspired design make in vivo tumor suppression by drug‐loaded viral mimics against BALB/c mice bearing 4T1 tumor greatly exceed the positive control group (more than three times). More importantly, viral mimics hold great potentials to reduce side effects and decrease tumor metastasis after systemic administration.

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