NIR‐Responsive Polycationic Gatekeeper‐Cloaked Hetero‐Nanoparticles for Multimodal Imaging‐Guided Triple‐Combination Therapy of Cancer

Abstract

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging-guided therapy of cancer. In this work, a near-infrared (NIR)-triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two-armed ethanolamine-modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD-PGEA) has been successfully fabricated for multimodal imaging-guided triple-combination treatment of cancer. A hierarchical hetero-structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X-ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl-rich CD-PGEA/pDNA complexes, realizing the co-delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR-triggered release of DOX through the facilitated detachment of CD-PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging-guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.

Smart Delivery Systems Based on Poly(glycidyl methacrylate)s‐Coated Organic/Inorganic Core–Shell Nanohybrids

“…In addition, dual‐modal PA/CT imaging‐guided trimodal complementary cancer therapy was achieved by integrating chemotherapy, GT, and PTT, as demonstrated by good in vivo performance. Subsequently, QDs and amantadine were successfully attached onto the surface of SiO 2 coated Au NRs to form Au NRs@SiO 2 ‐QDs/Ad (ASQ‐Ad), and then CD‐PGEA was assembled with ASQ‐Ad for NIR‐triggered release of DOX and pDNA via photothermal effect . This multifunctional nanoplatform innovatively integrated Au NRs with QDs, exhibiting enhanced trimodal fluorescent/PA/CT imaging‐guided gene/chemo/photothermal therapy for glioma tumors.…”

“…Subsequently, QDs and amantadine were successfully attached onto the surface of SiO 2 coated Au NRs to form Au NRs@SiO 2 -QDs/Ad (ASQ-Ad), and then CD-PGEA was assembled with ASQ-Ad for NIR-triggered release of DOX and pDNA via photothermal effect. [63] This multifunctional nanoplatform innovatively integrated Au NRs with QDs, exhibiting enhanced trimodal fluorescent/PA/CT imagingguided gene/chemo/photothermal therapy for glioma tumors. Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging-guided therapy of cancer.…”

Turn-On Supramolecular Host-Guest Nanosystems as Theranostics for Cancer

“…In 2017, another successful case using cyclodextrin was the construction of a near-infrared (NIR)-triggered multifunctional nanoplatform that combined fluorescent, photoacoustic, and tomography imaging with gene, chemo-, and photothermal therapy into one nanoparticle. 19 Recently, Lee and co-workers report functional gold nanoparticles (AuNPs) bearing a tumor pH-sensitive g-cyclodextrin cap, which showed marked potential for tumor therapy. 20 It is also noteworthy that the synergistic effects caused by combining CD units with polymeric backbones have been used advantageously in the construction of controlled and targeted drug-delivery systems.…”

Photoacoustic Drug Delivery

“…Duan et al designed a multimodal imaging-guided combination therapy system based on Au NRs [66]. The researchers first coated the Au NRs with mesoporous silica for loading of drug and quantum dots, and further decorated the system with adamantyl (Ad) groups and two-armed ethanolamine-modified poly(glycidyl methacrylate) with cyclodextrin cores (CD–PGEA) conjugates as gatekeeper (Figure 3).…”