Focused Ultrasound‐Augmented Delivery of Biodegradable Multifunctional Nanoplatforms for Imaging‐Guided Brain Tumor Treatment

Abstract

The blood brain barrier is the main obstacle to delivering diagnostic and therapeutic agents to the diseased sites of brain. It is still of great challenge for the combined use of focused ultrasound (FUS) and theranostic nanotechnology to achieve noninvasive and localized delivery of chemotherapeutic drugs into orthotopic brain tumor. In this work, a unique theranostic nanoplatform for highly efficient photoacoustic imaging‐guided chemotherapy of brain tumor both in vitro and in vivo, which is based on the utilization of hollow mesoporous organosilica nanoparticles (HMONs) to integrate ultrasmall Cu2− xSe particles on the surface and doxorubicin inside the hollow interior, is synthesized. The developed multifunctional theranostic nanosystems exhibit tumor‐triggered programmed destruction due to the reducing microenvironment‐responsive cleavage of disulfide bonds that are incorporated into the framework of HMONs and linked between HMONs and Cu2− xSe, resulting in tumor‐specific biodegradation and on‐demand drug‐releasing behavior. Such tumor microenvironment‐responsive biodegradable and biocompatible theranostic nanosystems in combination with FUS provide a promising delivery nanoplatform with high performance for orthotopic brain tumor imaging and therapy.

Photoacoustic Imaging: Contrast Agents and Their Biomedical Applications

“…PA imaging has also been widely used in brain imaging . For example, Sailor and co‐workers developed an effective PA contrast agent, Ca‐pSiNP‐ICG, in which ICG was encapsulated in porous silicon NPs via a calcium silicate precipitation method for ex vivo mouse‐brain imaging .…”

Disulfide‐Bridged Organosilica Frameworks: Designed, Synthesis, Redox‐Triggered Biodegradation, and Nanobiomedical Applications

“…The strategy of selective core etching of core–shell structured SiO 2 @MONs was developed to synthesize a series of HMONs with various framework components, based on the principle that SiC bonds within the MON shell are more stable than SiO bonds within the SiO 2 core . By using solid silica nanospheres as core, Shi and co‐workers synthesized several HMONs with one up to quintuple group‐bridged silsesquioxane framework using a mixture of BTEPTS (R 1 = disulfide), BTEB (R 2 = benzene), bis(triethoxysilyl)ethene (BTEEE, R 3 = ethene (CHCH)), BTEE (R 4 = ethane), and bis(triethoxysilyl)biphenyl (BTEBP, R 5 = biphenyl) ( Figure A) .…”

“…By using solid silica nanospheres as core, Shi and co‐workers synthesized several HMONs with one up to quintuple group‐bridged silsesquioxane framework using a mixture of BTEPTS (R 1 = disulfide), BTEB (R 2 = benzene), bis(triethoxysilyl)ethene (BTEEE, R 3 = ethene (CHCH)), BTEE (R 4 = ethane), and bis(triethoxysilyl)biphenyl (BTEBP, R 5 = biphenyl) ( Figure A) . In addition, by replacing solid silica nanospheres with small MSNs as cores, they prepared disulfide‐bridged HMONs with a particle size of ≈40 nm (Figure B) . Moreover, they synthesized HMONs with varied pore diameters by tuning the volume ratios (5:3, 5:6, 5:9, and 5:12) of TEOS to BTEPDS during the coating process, and achieved scale‐up synthesis of more than 10 g .…”

A Multifunctional Biodegradable Nanocomposite for Cancer Theranostics

“…[7][8][9] The latter are similar to mesoporous silicas, but rather than comprising pure SiO 2 contain organic functional groups within the silica framework. [14][15][16][17] For instance, Huang et al fabricated hollow MONs with a physiologically active disulfide bond (SS) incorporated into the silica framework. [10,11] Various organic moieties can be incorporated into MONs, and since these are intrinsic components of the framework they do not block the pore channels.…”

“…[10,11] Various organic moieties can be incorporated into MONs, and since these are intrinsic components of the framework they do not block the pore channels. [16] In other work, Chen and co-workers reported a nanotheranostic based on CuS-modified MONs for tumor-specific perfluoropentane delivery and multimodality imaging. [14][15][16][17] For instance, Huang et al fabricated hollow MONs with a physiologically active disulfide bond (SS) incorporated into the silica framework.…”