A Novel Instantaneous Self-Assembled Hollow MOF-Derived Nanodrug for Microwave Thermo-Chemotherapy in Triple-Negative Breast Cancer

Abstract

Hollow materials derived from metal–organic frameworks (MOFs) have emerged in the biomedical field due to their unique properties, and different synthesis methods have been proposed. However, so far, the large-scale use of hollow MOFs is mostly limited by the timeliness of synthesis methods. Herein, we propose a new ultrasonic aerosol flow strategy for the instantaneous synthesis of a Zr-MOF-derived hollow sphere complex (ZC-HSC) in only one step. Through rapid transient heating, the coordination between metal salts and organic ligands occurs along with prompt evaporation of the solvent. The whole process lasts for only about 21 s, compared with several steps that take hours or even days for conventional synthesis methods. Based on the ZC-HSC, we designed a nanodrug with the functions of manipulating the tumor microenvironment, which can reshape the tumor microenvironment by improving tumor hypoxia and inflammatory microenvironment and promoting antiangiogenic therapy. Combined with microwave thermo-chemotherapy, the nanodrugs effectively treat triple-negative breast cancer (the tumor cell survival rate was only 34.76 and 31.05% in normoxic and hypoxic states, respectively, and the tumor inhibition rate reached 87.9% at the animal level), providing a new theoretical basis for the treatment of triple-negative breast cancer. This rapid, one-step, and continuous ultrasonic aerosol flow strategy has bright prospects in the synthesis of MOF-derived hollow materials and promotes the further development of large-scale applications of biological nanomaterials.

Magnetic Bimetallic Heterointerface Nanomissiles with Enhanced Microwave Absorption for Microwave Thermal/Dynamics Therapy of Breast Cancer

“…To further expand the clinical application potential of MWT, a series of MW sensitizers with the aim of enhancing MW heating efficiency of tumor sites have been developed. − The heating principle of these MW sensitizers was mostly based on the ion confinement effect, a mechanism whereby the movement of ions within the confined space provided by the MW sensitizer is accelerated under MW irradiation to generate kinetic energy for further conversion into heat . Though they can improve the MW thermal effect of a tumor to a certain extent after being enriched in tumor sites, the uniformity of the induced thermal damage is still greatly limited by the ionic state within the cell, such as the concentration and the distribution of ions. − Recently, MW absorbing materials (MAMs), as a class of materials that can essentially promote the energy conversion between electromagnetic energy and thermal energy to generate excellent thermal effects, have attracted increasing attention and shown the potential to solve the limitations of existing MW thermal sensitizers. − Regrettably, the absorption frequencies of most MAMs are mainly distributed in the mid- and high-frequency bands, − and few have been reported to achieve strong microwave absorption (MA) performance at medical frequencies (433, 915, and 2450 MHz) . Therefore, developing MAMs with strong MA capacity in the medical frequency range is of great significance to further promote the clinical tumor treatment of MWT.…”

H2S-Reactivating Antitumor Immune Response after Microwave Thermal Therapy for Long-Term Tumor Suppression

“…9,10 To date, a variety of MW thermal sensitizers, mainly including inorganic and organic− inorganic hybrid nanoparticles, have been successfully developed for enhancing MW heating at tumor sites and reducing the induced MW thermal damage to adjacent tissues. 11−13 Multiple expanded strategies based on these MW thermal sensitizers have also been widely proposed with an attempt to achieve more comprehensive tumor suppression, for example, combining an MW sensitizer with chemotherapeutic drugs to construct an integrated platform for MW thermal sensitization and drug delivery 14,15 or endowing an MW thermal sensitizer with dynamic sensitization characteristics simultaneously to realize MW dynamic therapy-assisted MWTT. 16−18 Although the temporary inhib- itory effect has been extremely improved, the long-term antitumor outcomes are still disappointing, remaining the main obstacles impeding the further development of MWTT.…”

“…It has advantages of deep penetration, minimal invasion, repeatable operation, and low interference from bone and gas. − However, high microwave (MW) radiation energy that can kill tumor cells usually causes significant injury to adjacent normal tissues within the radiation range due to its nonselective nature . Moreover, residual sporadic lesions often still exist after MWTT, , and the infiltration of predominant myeloid suppressor cells (e.g., myeloid-derived suppressor cells (MDSCs)) in these residual lesions will be increased to induce the generation of immunosuppression, making tumor prone to recurrence and metastasis. , To date, a variety of MW thermal sensitizers, mainly including inorganic and organic–inorganic hybrid nanoparticles, have been successfully developed for enhancing MW heating at tumor sites and reducing the induced MW thermal damage to adjacent tissues. − Multiple expanded strategies based on these MW thermal sensitizers have also been widely proposed with an attempt to achieve more comprehensive tumor suppression, for example, combining an MW sensitizer with chemotherapeutic drugs to construct an integrated platform for MW thermal sensitization and drug delivery , or endowing an MW thermal sensitizer with dynamic sensitization characteristics simultaneously to realize MW dynamic therapy-assisted MWTT. − Although the temporary inhibitory effect has been extremely improved, the long-term antitumor outcomes are still disappointing, remaining the main obstacles impeding the further development of MWTT. Hence, weakening or even abolishing the immunosuppression after MWTT and further activating antitumor immune response for achieving long-lasting tumor inhibition will be of great importance.…”