pH/Ultrasound Dual‐Responsive Gas Generator for Ultrasound Imaging‐Guided Therapeutic Inertial Cavitation and Sonodynamic Therapy

Abstract

Herein, a pH/ultrasound dual-responsive gas generator is reported, which is based on mesoporous calcium carbonate (MCC) nanoparticles by loading sonosensitizer (hematoporphyrin monomethyl ether (HMME)) and modifying surface hyaluronic acid (HA). After pinpointing tumor regions with prominent targeting efficiency, HMME/MCC-HA decomposes instantaneously under the cotriggering of tumoral inherent acidic condition and ultrasound (US) irradiation, concurrently accompanying with CO generation and HMME release with spatial/temporal resolution. Afterward, the CO bubbling and bursting effect under US stimulus results in cavitation-mediated irreversible cell necrosis, as well as the blood vessel destruction to further occlude the blood supply, providing a "bystander effect." Meanwhile, reactive oxygen species generated from HMME can target the apoptotic pathways for effective sonodynamic therapy. Thus, the combination of apoptosis/necrosis with multimechanisms consequently results in a remarkable antitumor therapeutic efficacy, simultaneously minimizing the side effects on major organs. Moreover, the echogenic property of CO make the nanoplatform as a powerful ultrasound contrast agent to identify cancerous lesions. Based on the above findings, such all-in-one drug delivery platform of HMME/MCC-HA is utilized to provide the US imaging guidance for therapeutic inertial cavitation and sonodynamic therapy simultaneously, which highlights possibilities of advancing cancer theranostics in biomedical fields.

Metal–Organic‐Framework‐Derived Carbon Nanostructure Augmented Sonodynamic Cancer Therapy

“…Sonodynamic therapy (SDT), a novel strategy for cancer therapy, has led to widespread interest due to its safety, tissue penetration depth and low cost, etc . In SDT, ultrasound (US) can cause the irreversible and fetal damage to tumor cells via heat, cavitation, or sonosensitizers …”

Gas‐Generating Nanoplatforms: Material Chemistry, Multifunctionality, and Gas Therapy

“…The CO 2 ‐generating nanoplatforms were also developed for US‐guided therapeutics based on the inertial cavitation and further SDT . A multifunctional nanoplatform of pH/ultrasound dual‐responsive CO 2 generator was constructed based on mesoporous calcium carbonate nanoparticles (MCC NPs) loaded with hematoporphyrin monomethyl ether (HMME) as a sonosensitizer .…”

“…The CO 2 ‐generating nanoplatforms were also developed for US‐guided therapeutics based on the inertial cavitation and further SDT . A multifunctional nanoplatform of pH/ultrasound dual‐responsive CO 2 generator was constructed based on mesoporous calcium carbonate nanoparticles (MCC NPs) loaded with hematoporphyrin monomethyl ether (HMME) as a sonosensitizer . Meanwhile, hyaluronic acid with tumor‐targeting functionality as well as gatekeeper was modified onto MCC nanoparticles' surface, endowing the composite nanosystem with high tumor‐targeting efficacy and minimized premature of drug release ( Figure a).…”

“…e) Time‐dependent tumor‐growth curves after various treatments as indicated in the figure. Reproduced with permission . Copyright 2017, Wiley‐VCH.…”

PPy nanoneedle based nanoplatform capable of overcoming biological barriers for synergistic chemo-photothermal therapy

“…In recent years, the advancement in nanomaterials has drawn widespread attention for biomedical applications, especially for cancer therapy. [1][2][3][4] In particular, the near infrared (NIR) resonant nanoparticles have developed rapidly in the past few years for cancer treatment. 5,6 Under NIR irradiation, the photothermal agents absorbed energy from photons and converted it into heat, leading to tumor cellular structure damage or apoptosis for photothermal therapy (PTT).…”