GSH-activated Porphyrin Sonosensitizer Prodrug for Fluorescence Imaging-guided Cancer Sonodynamic Therapy.

Sonodynamic therapy (SDT), which uses ultrasound to trigger a sonosensitizer to generate reactive oxygen species (ROS), is a promising form of cancer therapy with outstanding tissue penetration depth. However, the sonosensitizer may inevitably spread to surrounding healthy tissue beyond the tumor, resulting in undesired side effects under an ultrasound stimulus. Herein, as glutathione (GSH) is overexpressed in the tumor microenvironment, a GSH-activatable sonosensitizer prodrug was designed by attaching a quencher to tetraphydroxy porphyrin for tumor therapy. The prodrug exhibited poor fluorescence and low ROS generation capacity under ultrasound irradiation but it can be activated by GSH to simultaneously switch on fluorescence emission and ROS generation in tumor site. Compared with the non-quenched sonosensitizer, the designed prodrug exhibited significantly higher tumor/healthy organ fluorescence ratios, due to the specific fluorescence and ROS activation by overexpressed GSH in the tumor. Finally, the prodrug exhibited efficient tumor growth inhibition under ultrasound irradiation, further demonstrating its promise as a GSH-activated sonosensitizer prodrug for highly effective cancer treatment.

A nanoparticle composed of totally hospital-available drugs and isotope for fluorescence/SPECT dual-modal imaging-guided photothermal therapy to inhibit tumor metastasis.

As primary sites of tumor metastasis, sentinel lymph nodes (SLNs) require a highly biocompatible theranostic platform for precise localization and treatment to inhibit tumor metastasis. Herein, indocyanine green-human serum albumin (ICG-HSA) nanoparticles (NPs) were fabricated by ICG-induced self-assembly and radiolabeled with technetuim-99 m (99mTc). The fabricated NPs were composed of hospital-available drugs and isotopes, making them highly biocompatible for in vivo applications. In a mouse model of SLN metastasis, the prepared NPs exhibited excellent capacity for preoperative planning by single-photon emission computed tomography (SPECT) imaging-enabled SLN localization, near-infrared fluorescence (NIRF) imaging-enabled intraoperative real-time monitoring, and SLN photothermal treatment. Photothermal treatment with SLN enhanced the inhibition of lung metastasis and significantly increased the survival time of mice. The prepared NPs were highly biocompatible and exhibited efficient theranostic properties for inhibiting cancer metastasis, making them promising candidates for clinical translation.

Correction: Facile synthesis of near-infrared bodipy by donor engineering for in vivo tumor targeted dual-modal imaging.

Correction for 'Facile synthesis of near-infrared bodipy by donor engineering for in vivo tumor targeted dual-modal imaging' by Feifei An et al., J. Mater. Chem. B, 2021, 9, 9308-9315, DOI: 10.1039/D1TB01883C.

Facile synthesis of near-infrared bodipy by donor engineering for in vivo tumor targeted dual-modal imaging.

Bodipy is one of the most popular dyes for bioimaging, however, a complicated synthetic protocol is needed to create and isolate ideal near-infrared (NIR) emissive Bodipy derivatives for optical bioimaging. It is noticed that the donor species impact the wavelength when the π-conjugation system of green light emissive Bodipy is elongated via a one-step reaction. Herein, several Bodipy dyes bearing different common donors are synthesized. Their optical properties confirm that both absorption and emission peaks of the synthesized Bodipy could be tuned to NIR wavelength by using stronger donors via a facile reaction. The synthesized monocarboxyl Bodipy could conjugate with aminated PEG to yield an amphiphilic polymer, which further self-assembles into a NIR nanoparticle (NP). The NIR NP exhibits preferential tumor accumulation via the enhanced permeation and retention (EPR) effect, making it useful for tumor diagnosis by both fluorescence imaging and photoacoustic tomography.

Chemodynamic nanomaterials for cancer theranostics.

It is of utmost urgency to achieve effective and safe anticancer treatment with the increasing mortality rate of cancer. Novel anticancer drugs and strategies need to be designed for enhanced therapeutic efficacy. Fenton- and Fenton-like reaction-based chemodynamic therapy (CDT) are new strategies to enhance anticancer efficacy due to their capacity to generate reactive oxygen species (ROS) and oxygen (O2). On the one hand, the generated ROS can damage the cancer cells directly. On the other hand, the generated O2 can relieve the hypoxic condition in the tumor microenvironment (TME) which hinders efficient photodynamic therapy, radiotherapy, etc. Therefore, CDT can be used together with many other therapeutic strategies for synergistically enhanced combination therapy. The antitumor applications of Fenton- and Fenton-like reaction-based nanomaterials will be discussed in this review, including: (iþ) producing abundant ROS in-situ to kill cancer cells directly, (ii) enhancing therapeutic efficiency indirectly by Fenton reaction-mediated combination therapy, (iii) diagnosis and monitoring of cancer therapy. These strategies exhibit the potential of CDT-based nanomaterials for efficient cancer therapy.

Magnetic resonance imaging-guided and targeted theranostics of colorectal cancer.

Colorectal cancer (CRC) is the most common gastrointestinal tract cancer worldwide and is associated with high morbidity and mortality. The development of nanosized drug delivery systems has provided a new direction in CRC treatment. Among these systems, magnetic nanoparticle (MNP)-based multifunctional platforms provide a novel strategy for magnetic resonance imaging (MRI)-related cancer theranostics. At the beginning of this original review, the carcinogenesis and treatment status of CRC are summarized. Then, diversified preparation and functionalization methods of MNPs are systematically analyzed, followed by MRI-involved theranostic strategies. The latest progress in MRI-mediated multimode diagnosis and image-guided targeted therapy in CRC management is the main focus. Finally, the major challenges in promoting MRI-induced precise theranostics of CRC in clinical practice are discussed.

Hypoxia-activated nanomedicines for effective cancer therapy.

Hypoxia, a common characteristic in solid tumors, is found in phenotypically aggressive cancers that display resistance to typical cancer interventions. Due to its important role in tumor progression, tumor hypoxia has been considered as a primary target for cancer diagnosis and treatment. An advantage of hypoxia-activated nanomedicines is that they are inactive in normoxic cells. In hypoxic tumor tissues and cells, these nanomedicines undergo reduction by activated enzymes (usually through 1 or 2 electron oxidoreductases) to produce cytotoxic substances. In this review, we will focus on approaches to design nanomedicines that take advantage of tumor hypoxia. These approaches include: i) inhibitors of hypoxia-associated signaling pathways; ii) prodrugs activated by hypoxia; iii) nanocarriers responsive to hypoxia, and iv) bacteria mediated hypoxia targeting therapy. These strategies have guided and will continue to guide nanoparticle design in the near future. These strategies have the potential to overcome tumor heterogeneity to improve the efficiency of radiotherapy, chemotherapy and diagnosis.

Small ultra-red fluorescent protein nanoparticles as exogenous probes for noninvasive tumor imaging in vivo.

Nanoparticles are excellent imaging agents for cancer, but variability in chemical structure, racemic mixtures, and addition of heavy metals hinders FDA approval in the United States. We developed a small ultra-red fluorescent protein, named smURFP, to have optical properties similar to the small-molecule Cy5, a heptamethine subclass of cyanine dyes (Ex/Em = 642/670 nm). smURFP has a fluorescence quantum yield of 18% and expresses so well in E. coli, that gram quantities of fluorescent protein are purified from cultures in the laboratory. In this research, the fluorescent protein smURFP was combined with bovine serum albumin into fluorescent protein nanoparticles. These nanoparticles are fluorescent with a quantum yield of 17% and 12-14 nm in diameter. The far-red fluorescent protein nanoparticles noninvasively image tumors in living mice via the enhanced permeation and retention (EPR) mechanism. This manuscript describes the use of a new fluorescent protein nanoparticle for in vivo fluorescent imaging. This protein nanoparticle core should prove useful as a biomacromolecular scaffold, which could bear extended chemical modifications for studies, such as the in vivo imaging of fluorescent protein nanoparticles targeted to primary and metastatic cancer, theranostic treatment, and/or dual-modality imaging with positron emission tomography for entire human imaging.