Herein, smart Au nanorod@dendrimer-assembly nanohybrids (AuNR@DA NHs) were developed for adapting sequential biological barriers and remodeling tumor permeability, thereby achieving multimodal enhancement of penetration and internalization in multidrug-resistant poorly-permeable tumors.

Although biomimetic virus‐like strategies have been widely used in antitumor applications, construction of uniquely shaped virus‐like agents and optimization of their specific morphological features to achieve diverse antitumor functions are worthwhile pursuits. Here, a novel strategy to construct an artificial tobacco mosaic virus (ATMV) that closely mimics the structure of the rod‐like tobacco mosaic virus (TMV) is developed. The supramolecular array is self‐assembled from small, repeated subunits of tailor‐made capsid‐mimicking dendrons onto RGD‐modified single‐walled carbon nanotube to construct the ATMVs with high structural stability. The ATMVs are tactfully designed with shielding, targeting, and arming approaches, including shielding the viruses against premature elimination, selectively targeting tumor tissue, and arming the viruses with oncolytic abilities. The elongated particles are concealed in blood until they arrived at a tumor site, then they induce robust composite oncolytic processes including cytomembrane penetration, endoplasmic reticulum disruption to cause Ca2+ release, chemotherapeutic delivery, and photothermal therapy. Excitingly, the ATMVs not only lyse primary infected cells, but permeate adjacent cells for secondary infection, spreading cell‐to‐cell and continuing to induce lysis even deep in solid tumors. This work inspires a uniquely shaped virus‐like agent with tactically optimized oncolytic functions that completely defeated large drug‐resistant colon tumor (LoVo/Adr, ≈500 mm3).

We developed a biocompatible triple-responsive dendrimeric nanocage (TDN) through a simple method for targeted drug delivery.

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Morphology genetic biomedical materials (MGBMs), referring to fabricating materials by learning from the genetic morphologies and strategies of natural species, hold great potential for biomedical applications. Inspired by the cargo-carrying-bacterial therapy (microbots) for cancer treatment, a MGBM (artificial microbots, AMBs) was constructed. Rather than the inherent bacterial properties (cancerous chemotaxis, tumor invasion, cytotoxicity), AMBs also possessed ingenious nitric oxide (NO) generation strategy. Mimicking the bacterial construction, the hyaluronic acid (HA) polysaccharide was induced as a coating capsule of AMBs to achieve long circulation in blood and specific tissue preference (tumor tropism). Covered under the capsule-like polysaccharide was the combinatorial agent, the self-assembly constructed by the amphiphilic dendrons with abundant l-arginine residues peripherally (as endogenous NO donor) and hydrophobic chemotherapeutic drugs at the core stacking on the surface of SWNTs (the photothermal agent) for a robust chemo-photothermal therapy (chemo-PTT) and the elicited immune therapy. Subsequently, the classic inducible nitric oxide synthase (iNOS) pathway aroused by immune response was revolutionarily utilized to oxidize the l-arginine substrates for NO production, the process for which could also be promoted by the high reactive oxygen species level generated by chemo-PTT. The NO generated by AMBs was intended to regulate vasodilation and cause a dramatic invasion (as the microbots) to disperse the therapeutic agents throughout the solid tumor for a much more enhanced curative effect, which we defined as “self-propulsion”. The self-propelled AMBs exhibiting impressive primary tumor ablation, as well as the distant metastasis regression to conquer the metastatic triple negative breast cancer, provided pioneering potential therapeutic opportunities, and enlightened broad prospects in biomedical application.

Combinatorial short interference RNA (siRNA) technology for silencing of multiple genes is expected to provide an effective therapeutic approach for cancer with complex genetic mutation and dysregulation. Herein we present...

Multidrug resistance is one of the major problems in chemotherapy, and exploiting impactful targets to reverse drug resistance of most tumors remains a difficult problem. In this study, the tumor‐oriented nanoparticle, BIBR1532‐loaded peptide dendrimeric prodrug nanoassembly (B‐PDPN), is used to assist telomerase inhibition for multidrug resistance reversal. B‐PDPN possesses the characteristics of an acid‐activated histidine to promote cellular uptake, a redox‐sensitive poly(ethylene glycol) (PEG) layer to actualize endosomal escape and telomerase inhibitor release, and an acid sensitive chemical bond to facilitate chemotherapeutic drug release. Telomerase termination weakens the protective effect of hTERT protein on mitochondria and enhances reactive oxygen species (ROS) production, which increases DNA damage and apoptosis. The tumor‐oriented nanoparticle B‐PDPN achieves a broad‐spectrum telomerase inhibition to combat multidrug resistance. In vivo experiments support the evidence that B‐PDPN accumulates in the tumor site and reduces the expression of hTERT in tumor tissues to inhibit drug resistant tumor growth. This work introduces an innovative strategy of utilizing features of tumor‐activated nanoplatform to assist telomerase termination. The nanoplatform enhances intracellular drug concentration and nucleus delivery of doxorubicin (DOX), and promotes DNA damage to combat multidrug resistance.

No abstract