Development of FL/MR dual-modal Au nanobipyramids for targeted cancer imaging and photothermal therapy.

Multifunctional nanodrugs have emerged as an effective platform to integrate multiple imaging and therapeutic functions for tremendous biomedical applications. However, the development of a simple potent theranostic nanoplatform is still an intractable challenge. Herein, a novel theranostic nanoplatform was developed by coupling prepared Au nanobipyramids with Gd2O3, Au nanoclusters and denatured bovine serum albumin (AuNBP-Gd2O3/Au-dBSA) for FL/MR dual-modal imaging guided photothermal therapy. AS1411 aptamers were conjugated to enhance its targetability towards breast cancer. The AS1411-AuNBP-Gd2O3/Au-dBSA suspension could be readily heated above 40 °C at a low concentration (2 mg/L) and NIR density (1 W/cm2). The AS1411-AuNBP-Gd2O3/Au-dBSA revealed a fluorescence quantum yield of 4.2% and higher longitudinal relaxivity rate of 6.75 mM-1 s-1 compared to Gd-DTPA of 4.45 mM-1 s-1. As a result, the AS1411-AuNBP-Gd2O3/Au-dBSA functions as a multimodal nanoprobe of photothermal, fluorescence and MR imaging for specific tumor diagnosis and guidance of therapy, which was validated via in vitro and in vivo tests. Moreover, AS1411-AuNBP-Gd2O3/Au-dBSA nanoparticles indicated excellent photothermal anticancer effect more than 95% in both in vitro and in vivo tests. Besides, the low toxicity of AS1411-AuNBP-Gd2O3/Au-dBSA nanocomposites was further confirmed in vitro and in vivo. Thus, these results demonstrated the AS1411-AuNBP-Gd2O3/Au-dBSA nanocomposites as a rational design of multifunctional nanoplatform to enable multimodal imaging guided photothermal therapy.

Grade-targeted nanoparticles for improved hypoxic tumor microenvironment and enhanced photodynamic cancer therapy.

Background: The hypoxia of the tumor microenvironment (TME), low transfer efficiency of photosensitizers and limited diffusion distance of reactive oxygen species restrict the application of photodynamic therapy (PDT). Aim: To produce TME-responsive and effective nanoparticles for sensitizing PDT. Materials & methods: CD44 and mitochondria grade-targeted hyaluronic acid (HA)-triphenylphosphine (TPP)-aminolevulinic acid (ALA)-catalase (CAT) nanoparticles (HTACNPs) were synthesized via a modified double-emulsion method. In vitro and in vivo experiments were performed to investigate the antitumor efficacy of HTACNP-mediated PDT. Results: HTACNPs specifically targeted MV3 cells and the mitochondria and produced O2 to relieve TME hypoxia. HTACNP-mediated PDT produced reactive oxygen species to induce irreversible cell apoptosis. HTACNP-PDT inhibited melanoma growth effectively in vivo. Conclusion: HTACNP-mediated PDT improved TME hypoxia and effectively enhanced PDT for cancer.

Polydopamine-Based Nanoparticles for Photothermal Therapy/Chemotherapy and their Synergistic Therapy with Autophagy Inhibitor to Promote Antitumor Treatment.

Polydopamine (PDA) has attracted much attention recently due to its strong adhesion capability to most substrates. After combining with organic (such as organic metal framework, micelles, hydrogel, polypeptide copolymer) or inorganic nanomaterials (such as gold, silicon, carbon), polydopamine-based nanoparticles (PDA NPs) exhibit the merging of characteristics. Until now, the preparation methods, polymerization mechanism, and photothermal therapy (PTT) or chemotherapy (CT) applications of PDA NPs have been reported detailly. Since the PTT or CT treatment process is often accompanied by exogenous stimuli, tumor cells usually induce pro-survival autophagy to protect the cells from further damage, which will weaken the therapeutic effect. Therefore, an in-depth understanding of PDA NPs modulated PTT, CT, and autophagy is required. However, this association is rarely reviewed. Herein, we briefly described the relationship between PTT/CT, autophagy, and tumor treatment. Then, the outstanding performances of PDA NPs in PTT/CT and their combination with autophagy inhibitors for tumor synergistic therapy have been summarized. This work is expected to shed light on the multi-strategy antitumor therapy applications of PDA NPs.

Targeted MRI and chemotherapy of ovarian cancer with clinic available nano-drug based nanoprobe.

Cancer is the leading cause of death worldwide, and chemotherapy, as its main treatment, has side effects in clinical application due to lack of targeting selectivity to tumor tissues. Theranostic nanomaterials have shown wonderful functions for the diagnosis and therapy of disease benefitting from the controllability of nanomaterials. However, there is still little available for clinical transformation due to the uncertain biocompatibility. It is urgent to develop nanoprobes possessing bright transformation potentials. This study reports a facile biomineralization route to synthesize the theranostic nanoprobe using the clinic available nano-drug (trademark Abraxane). Further profiting from the binding ability of albumin to metal cations, we successfully prepared biocompatible nanoprobe, BSA-Gd2O3/PTX@Anti-HE4 mAb, for the targeted magnetic resonance imaging and chemotherapy of ovarian carcinoma. The obtained nanoprobe has the advantages of uniform particle size, good dispersibility and favorable stability. In vivo and in vitro experiment results showed that the nanoprobe can realize targeted magnetic resonance imaging and chemotherapy of ovarian carcinoma. Such a novel multifunctional nanoprobe based on clinic nano-drug might be promising for clinic transformation.

Near-infrared laser-induced phase-shifted nanoparticles for US/MRI-guided therapy for breast cancer.

Breast cancer is a refractory malignancy particularly in women, with an accruing morbidity and mortality worldwide. The purpose of this study was to evaluate the efficacy of laser-induced near-infrared (NIR) PFP/Gd-DTPA/ICG@PLGA NPs (PGINPs) in US/MR imaging and regimen for breast cancer; gadolinium-DTPA (Gd-DTPA), perfluoropentane (PFP) and indocyanine green (ICG) were wrapped in the poly (lactic-co-glycolic) acid (PLGA) shell membrane via a double emulsion approach. In this study, under the irradiation of NIR laser, the ICG enriched in the cancerous tissue not only converted optic energy into thermal energy to rapidly heat up the cancer focus but also convert O2 to singlet oxygen (1O2), which can effectively destroy the cancer tissues through photothermal therapy (PTT) and photodynamic therapy (PDT). Meanwhile, the thermal energy thus generated could promote the gasification of PFP to enable visualization of cancer tissues under US imaging. Gd-DTPA in combination with US imaging can also significantly enhance MR imaging to provide US/MR dual-modal imaging. This study proves the efficacy of NIR-inspired multifunctional nano-system PGINPs to potentiate US/MR imaging and regimen for breast cancer.

Activatable MRI-monitoring gene delivery for the theranostic of renal carcinoma.

Multifunctional nanocarriers, which can be used for molecular imaging and drug delivery simultaneously, favor the fabrication of theranostic platforms in a less cost- and time-consuming way. Polyethylene glycol (PEG)-modified manganese dioxide (MnO2) nanosheets (PEG-MnO2), used as two-dimensional nanomaterials, not only possess the high surface-to-volume ratio necessary for drug delivery but also display a redoxable property in the tumor microenvironment, producing Mn2+ ions for magnetic resonance imaging (MRI). In this study, we constructed a PEG-MnO2-OPN siRNA nanocomplex via a modular streptavidin bridge for the theranostic treatment of renal carcinoma in vitro and in vivo. This strategy of utilizing PEG-MnO2 nanosheets for OPN siRNA delivery showed effective tumor growth inhibition of 786-O tumor-bearing mice, and such a process could be monitored by the activated T1-weight MRI, illustrating the promising potential of PEG-MnO2 nanosheets for the fabrication of an MRI-based theranostic system.

Preparation of gadolinium doped carbon dots for enhanced MR imaging and cell fluorescence labeling.

Gadolinium doped carbon dots (Gd-CDs) were prepared as a dual-modal imaging agent for enhanced MR imaging and cell fluorescence imaging. The Gd-CDs were synthesized via one-step solvent free technique with Gd-DTPA and l-arginine as the Gd and carbon sources with a quantum yield of 57.78%. The Gd-CDs exhibited good crystal structure, excellent aqueous dispersity, high colloidal stability, intense fluorescence and low cytotoxicity. The bio-TEM images revealed that the Gd-CDs could be easily internalized by cancer cells and escape from the endosomes. Furthermore, the Gd-CDs demonstrated wonderful multi-color fluoresence cell labeling ability at various excitation wavelength and much better MR contrast effect compared with commercial Gd-DTPA with a high r1 relaxivity value 6.27 mM-1s-1. In addition, Gd-CDs exhibited brighter MR signal than Gd-DTPA in the animal MR imaging test. Finally, the Gd-CDs also indicated low long-term toxicity by the serum biochemistry analysis. Thus, these results indicated that Gd-CDs would be an excellent dual-modal imaging probe for enhanced MR imaging and fluorescence imaging.