Synergistic inhibition of metastatic breast cancer by dual-chemotherapy with excipient-free rhein/DOX nanodispersions

Abstract

Background: The management of metastatic cancer remains a major challenge in cancer therapy worldwide. The targeted delivery of chemotherapeutic drugs through rationally designed formulations is one potential therapeutic option. Notably, excipient-free nanodispersions that are entirely composed of pharmaceutically active molecules have been evaluated as promising candidates for the next generation of drug formulations. Formulated from the self-assembly of drug molecules, these nanodispersions enable the safe and effective delivery of therapeutic drugs to local disease lesions. Here, we developed a novel and green approach for preparing nanoparticles via the selfassembly of rhein (RHE) and doxorubicin (DOX) molecules, named RHE/DOX nanoparticles (RD NPs); this assembly was associated with the interaction force and did not involve any organic solvents. Results: According to molecular dynamics (MD) simulations, DOX molecules tend to assemble around RHE molecules through intermolecular forces. This intermolecular retention of DOX was further improved by the nanosizing effect of RD NPs. Compared to free DOX, RD NPs exerted a slightly stronger inhibitory effect on 4T1 cells in the scratch healing assay. As a dual drug-loaded nanoformulation, the efficacy of RD NPs against tumor cells in vitro was synergistically enhanced. Compared to free DOX, the combination of DOX and RHE in nanoparticles exerted a synergistic effect with a combination index (CI) value of 0.51 and showed a stronger ability to induce cell apoptosis. Furthermore, the RD NP treatment not only effectively suppressed primary tumor growth but also significantly inhibited tumor metastasis both in vitro and in vivo, with a better safety profile. Conclusions: The generation of pure nanodrugs via a self-assembly approach might hold promise for the development of more efficient and novel excipient-free nanodispersions, particularly for two small molecular antitumor drugs that potentially exert synergistic antiproliferative effects on metastatic breast cancer.

Carrier-free multifunctional nanomedicine for intraperitoneal disseminated ovarian cancer therapy

“…Carrier-free nanomedicines have drawn great attention due to the high load rate and nontoxic side effects of exogenous carriers [23,24]. In vivo studies have shown that nanomedicine exhibited longer blood half-life, better tumor selectivity, enhanced tumor accumulation, and significantly improved antitumor efficacy compared with free drugs [25,26].…”

Iron Oxyhydroxide Nanorods Coated with Poly(acrylic acid) to Reprogram Tumor-Associated Macrophages for Antitumor Immunotherapy

“…Figures b and S17 indicate that DP FeOOH NRs were mainly distributed in the liver and lung. Compared with the DOX group, the mice treated with DP FeOOH NRs had higher DOX accumulation in tumor tissues due to the enhanced permeation and retention (EPR) effect of drug delivery, which can conquer the poor potency of DOX to induce ICD. ,, After being intravenously injected with PBS, DOX, P FeOOH, and DP FeOOH NRs, the HMGB1 and calreticulin expression and the percentages of M1 and M2 macrophages within the suspension cells from the tumor tissues were analyzed after 3 days postinjection. The enhanced HMGB1 (Figure S18) and calreticulin (Figure S19) expression in the DP FeOOH NR group was achieved in vivo , presenting a similar result as shown in vitro .…”

Emerging Exosomes and Exosomal MiRNAs in Spinal Cord Injury

“…Because of the rapid advancement of science and technology, the research on TCMs continues to deepen. Previous preclinical and clinical findings have revealed that free TCMs can play an essential role in treating the pathophysiology of many diseases, including cancer (Wang R. et al, 2020), diabetes , Alzheimer's disease , depression (Zhu et al, 2020), and COVID-19 (Pan et al, 2020;Tian J. et al, 2020). In addition, some researchers have begun to focus their study on how to treat CNS injuries more effectively by using exosomes as drug delivery vehicles, these carrying TCMs to specific areas and exerting therapeutic effects.…”