Bone-Targeted Supramolecular Nanoagonist Assembled by Accurate Ratiometric Herbal-Derived Therapeutics for Osteoporosis Reversal.

Developing novel strategies for defeating osteoporosis has become a world-wide challenge with the aging of the population. In this work, novel supramolecular nanoagonists (NAs), constructed from alkaloids and phenolic acids, emerge as a carrier-free nanotherapy for efficacious osteoporosis treatment. These precision nanoagonists are formed through the self-assembly of berberine (BER) and chlorogenic acid (CGA), utilizing noncovalent electrostatic, π-π, and hydrophobic interactions. This assembly results in a 100% drug loading capacity and stable nanostructure. Furthermore, the resulting weights and proportions of CGA and BER within the NAs are meticulously controlled with strong consistency when the CGA/BER assembly feed ratio is altered from 1:1 to 1:4. As anticipated, our NAs themselves could passively target osteoporotic bone tissues following prolonged blood circulation, modulate Wnt signaling, regulate osteogenic differentiation, and ameliorate bone loss in ovariectomy-induced osteoporotic mice. We hope this work will open a new strategy to design efficient herbal-derived Wnt NAs for dealing with intractable osteoporosis.

Bioinspired Artificial Tobacco Mosaic Virus with Combined Oncolytic Properties to Completely Destroy Multidrug-Resistant Cancer.

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 ).

Novel nanoparticles generated by polymeric amphiphiles with pi-pi conjugated small molecules for anti-tumor drug delivery.

In recent years, the self-assembly polymeric nanoparticles are widely used for anti-tumor drug delivery. Multiple interactions such as hydrogen bonding, host-guest interaction, hydrophobic interaction and electrostatic interaction have been utilized to generate the nanoparticles. Herein, a new polymeric amphiphile with methoxy poly(ethylene glycol) (mPEG) as hydrophilic block and pi-pi conjugated small molecule N-(9-Fluorenylmethoxycarbonyl)-L-phenylalanines (Fmoc-Phe-OH) instead of hydrophobic polymer chain as lipophilic segment was synthesized. Anti-tumor drug doxorubicin (DOX) was trapped in the self-assembly nanoparticles via the dual hydrophobic and pi-pi stacking interactions. The synthesis and morphology of the self-assembly nanoparticles were studied. The interactions between drug and carrier, release profile, cellular uptake and in vitro anti-tumor efficiency of the drug loaded nanoparticles were investigated in details. The results showed that the amphiphiles self-assembled into spindle nanoparticles with the size around 200 nanometers. The pi-pi stacking interaction between DOX and Fmoc-Phe-OH achieved great performance for the efficient drug encapsulation. The DOX could be sustaingly released for 50 hours. The drug loaded nanoparticles were internalized in HepG2 cancer cells efficiently and exhibited good anti-tumor activity in vitro. The nanoparticles generated by mPEG-Phe-Fmoc amphiphiles provided a new strategy to fabricate polymeric nanoparticles for anti-tumor drug delivery.