Transforming the Chemical Structure and Bio‐Nano Activity of Doxorubicin by Ultrasound for Selective Killing of Cancer Cells

Abstract

Reconfiguring the structure and selectivity of existing chemotherapeutics represents an opportunity for developing novel tumor‐selective drugs. Here, as a proof‐of‐concept, the use of high‐frequency sound waves is demonstrated to transform the nonselective anthracycline doxorubicin into a tumor selective drug molecule. The transformed drug self‐aggregates in water to form ≈200 nm nanodrugs without requiring organic solvents, chemical agents, or surfactants. The nanodrugs preferentially interact with lipid rafts in the mitochondria of cancer cells. The mitochondrial localization of the nanodrugs plays a key role in inducing reactive oxygen species mediated selective death of breast cancer, colorectal carcinoma, ovarian carcinoma, and drug‐resistant cell lines. Only marginal cytotoxicity (80–100% cell viability) toward fibroblasts and cardiomyocytes is observed, even after administration of high doses of the nanodrug (25–40 µg mL−1). Penetration, cytotoxicity, and selectivity of the nanodrugs in tumor‐mimicking tissues are validated by using a 3D coculture of cancer and healthy cells and 3D cell‐collagen constructs in a perfusion bioreactor. The nanodrugs exhibit tropism for lung and limited accumulation in the liver and spleen, as suggested by in vivo biodistribution studies. The results highlight the potential of this approach to transform the structure and bioactivity of anticancer drugs and antibiotics bearing sono‐active moieties.

Polymeric micelle-based nanoagents enable phototriggering combined chemotherapy and photothermal therapy with high sensitivity

“…4d is the accumulation of nanomicelles in the lung, liver and spleen in both nanomicelle cases, which is plausibly ascribed to the enrichment of macrophages in these organs in our tumor-bearing model mice. 48,49 It should also be noted that further calculation of the signal ratio of the tumor/lung revealed an appreciable discrepancy in terms of targeting ability. Specifically, the ratio in the IR@MFH group was ∼2.08, while that in the IR@M group was ∼1.14.…”

Hypoxia Inhibitor Combined with Chemotherapeutic Agents for Antitumor and Antimetastatic Efficacy against Osteosarcoma

“…DOX is generally thought to have two main antitumor mechanisms: one is binding with DNA and inhibiting its replication; the other is destroying the mitochondrial respiratory chain and producing ROS. 39 When DOX enters the mitochondria, electrons are obtained from the electron transport chain (ETC), semiquinone intermediates are formed, and then the electrons are transferred to oxygen (O 2 ) through a redox reaction to produce ROS. 11 Therefore, to explore the antitumor mechanism of AD@PLGA−PEG NPs, we first investigated their intracellular accumulation.…”

“…This result was consistent with the literature report. 39 Therefore, we speculated that if the AD@PLGA−PEG NPs mainly entered the mitochondria and produced ROS, ABZ could help to produce more ROS so the AD@PLGA−PEG NPs could show a good inhibitory effect on tumor cells.…”

Sonosynthesis of nanobiotics with antimicrobial and antioxidant properties

“…Based on laboratory scale reactions, it has been found that acoustic cavitation derived from sound waves can promote chemical modification, polymerization and self-assembly of phenolic molecules into nanoparticles without using external chemical agents [14] , [21] , [22] , [23] . Bhangu et al have reported the synthesis of a carrier-free nanodrug made from non-selective anthracycline doxorubicin into a tumour selective drug nanoparticle by using high-frequency ultrasound [24] . It was demonstrated that the oscillating surface of acoustic cavitation bubbles acts as a catalytic binding site, inducing self-assembly of modified molecules at transient gas-liquid interfaces as a result of high local concentration and strong intermolecular interactions upon bubble implosion.…”